BuzzSugar

Five Essential Epsiodes: Friday Night Lights

BuzzSugar — Thu, 08 Jan 2009 11:30:06 -0800

Have you ever meant to get into a TV show but never had the time - till suddenly it was a few seasons in and you feared you'd never get caught up? That's what inspired this new occasional feature, Five Essential Episodes. Kind of like Getting Into for television, I'll choose the five episodes of a current show that are the most important for new fans to check out.

The first show I'm tackling is Friday Night Lights, which returns to start its third season on NBC on Jan. 16 after previously airing on DirecTV. I've seen a number of the DirecTV episodes and can say they're outstanding; I imagine many of them would end up on a future list of essentials. But for now, I'm sticking to episodes that aired in the first and second seasons. For the record, I'm assuming you know the premise and/or can also get your hands on the pilot episode. That said, here are my five essential episodes:

"Wind Sprints" - The third episode of the show's first season had one of the most iconic images of the series: the whole team running sprints up and down a sloppy, muddy hill in the rain, followed by Coach Taylor making Tim Riggins walk home while everyone else takes the bus. I'm not sure what falls harder when I watch this one: the rain or my tears.
"Black Eyes and Broken Hearts" - This season one episode comes on the heels of a walkout by the team's black players - led by star Smash Williams - over a racially charged comment made by an assistant coach. It's a great balance of FNL's meatier moments (the walkout story, the Taylors worrying about Julie's friendship with bad girl Tyra) and lighter ones (Matt trying to buy a gift for Julie).

To see the other three, read more.

"Mud Bowl" - There's just something about rain that must bring out the best in FNL. This gem comes toward the end of the first season and includes not just a football game in a mucky field but some juicy developments with Jason Street, Landry waving around Our Bodies, Ourselves, and a really shocking Tyra-related twist that would unfortunately lead to some of the worst parts of season two - but it seemed right at the time!

"State" - To think, the first-season finale could have been the final FNL ever! And what a satisfying episode it is, with the Panthers taking on their toughest football foe yet, Tami getting some information that will change her family's lives forever, and one of the most awkward and cold motivational speeches in the history of football.
"Leave No One Behind" - The second season was a little rough for FNL, but the show was back on track by the time this episode rolled around. The most stunning scene comes when Coach Taylor literally throws Matt in a cold shower, but Smash's sudden doubts about playing college ball bring up some shiver-inducing moments of their own.

FNL fans, what's on your list of essentials?

Photos courtesy of NBC

The Hills Beauty Quiz: Episode 1, "It's On B*tch"

BellaSugar — Wed, 30 Sep 2009 11:00:16 -0700

It's been almost exactly five years since we first saw Kristin Cavallari make her debut on Laguna Beach, and now she's back in action, essentially taking Lauren Conrad's place on The Hills. Everyone seems to be apprehensive about Kristin's return, and with good reason. During a pool party with the gang, she immediately makes a beeline for Justin, Audrina's ex-boyfriend. In the meantime, Heidi and Spencer search for their dream home, with Spencer putting a deposit down without first consulting his wife. All dramatic story lines aside, how closely were you paying attention to the beauty details of this episode? Test your knowledge now, and be sure to check out all the fashion on CelebStyle, too.

Photo courtesy of MTV

Take the quiz

Depression

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the Food and Drug Administration (FDA) approved the atypical antipsychotic drug aripiprazole (Abilify) for treatment of major depression in adults. Aripiprazole is used for treatment of schizophrenia and bipolar disorder. For depression, it is used in combination with antidepressant drug therapy. Researchers are also investigating other atypical antipsychotics for major depression treatment.

Antidepressants and Suicide Risk

In 2007, the FDA proposed adding new information to antidepressant warning labels concerning the increased risk for suicidal thinking and behavior among young adults ages 18 - 24 during the initial months of drug therapy.
The benefits of antidepressants for children and adolescents outweigh their potential risks, suggests a 2007 study in the Journal of the American Medical Association.

Antidepressants During Pregnancy

Most selective serotonin reuptake inhibitors (SSRIs) do not significantly increase the risk for birth defects when taken during early pregnancy, indicate several 2007 studies in the New England Journal of Medicine. However, some SSRIs -- such as paroxetine (Paxil) -- carry a higher risk than others. Researchers are still studying the overall safety of SSRIs during pregnancy. Women with depression should discuss with their doctors all potential risks and benefits.

Introduction

Everyone experiences some unhappiness, often as a result of a change, either in the form of a setback or a loss, or simply, as Freud said, "everyday misery." The painful feelings that accompany these events are usually appropriate, necessary, and transitory, and can even present an opportunity for personal growth. However, when depression persists and impairs daily life, it may be an indication of a depressive disorder. Severity, duration, and the presence of other symptoms are the factors that distinguish normal sadness from a depressive disorder.

Depression has been alluded to by a variety of names in both medical and popular literature for thousands of years. Early English texts refer to "melancholia," which was for centuries the generic term for all emotional disorders.

Depression is now referred to as a mood disorder, and the primary subtypes are major depression, dysthymia (chronic and usually milder depression), and atypical depression. Other important forms of depression are premenstrual dysphoric disorder (PDD or PMDD) and seasonal affective disorder (SAD).

Depression is defined as a mood disorder, and there are several subtypes. Bipolar disorder, also known as manic-depressive illness, is considered in a separate category.

The other major mood disorder is bipolar disorder, or manic-depressive illness, which is characterized by periods of depression alternating with episodes of excessive energy and activity. Bipolar disorder is not discussed in this report. [For more information, see In-Depth Report #66: Bipolar disorder.]

In major, or acute, depression, at least five of the symptoms listed below must occur for a period of at least 2 weeks, and they must represent a change from previous behavior or mood. Depressed mood or loss of interest must be present. Symptoms include:

1. Depressed mood on most days for most of each day -- irritability may be prominent in children and adolescents

2. Total or very noticeable loss of pleasure most of the time

3. Significant increases or decreases in appetite, weight, or both

4. Sleep disorders, either insomnia or excessive sleepiness, nearly every day

5. Feelings of agitation or a sense of intense slowness

6. Loss of energy and a daily sense of tiredness

7. Sense of guilt or worthlessness nearly all the time

8. Inability to concentrate occurring nearly every day

9. Recurrent thoughts of death or suicide

In addition, other criteria must be met:

The symptoms listed above do not follow or accompany manic episodes (such as in bipolar disorder or other disorders).
They impair important normal functions (such as work or personal relationships).
They are not caused by drugs, alcohol, or other substances.
They are not caused by normal grief.

A long-term study found that episodes of major depression usually last about 20 weeks. Between 30 - 40% of depressed patients experience sudden attacks of anger that they describe as uncharacteristic and inappropriate.

Click the icon to see an image of childhood depression.

Dysthymia, or chronic depression, afflicts 3 - 6% of the general population and is characterized by many of the same symptoms that occur in major depression. Symptoms of dysthymia are less intense and last much longer, at least 2 years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities. Possibly because of the duration of the symptoms, patients who suffer from chronic minor depression do not exhibit marked changes in mood or in daily functioning, although they have low energy, a general negativity, and a sense of dissatisfaction and hopelessness.

Double Depression. Often, symptoms become more severe over time. In one long-term study, nearly all patients with dysthymia suffered at least one episode of major depression superimposed over chronic depression (sometimes called double depression) at some time in their life. Some experts believe that such double depression should be considered as part of the natural course of dysthymic disorder. Women may be more susceptible to double depression. In one study, more than one-third of those who recovered from dysthymia relapsed within 5 years.

About a third of patients with depression have atypical depression. Symptoms include overeating and oversleeping. Such patients tend to have a feeling of being weighed down and react strongly to rejection. It tends to occur more in women, unmarried people, and those with other emotional disorders, such as anxiety or substance abuse. It also may impair functioning more severely than ordinary depression does.

Seasonal affective disorder (SAD) is characterized by annual episodes of depression during fall or winter that remit in the spring or summer. Other SAD symptoms include fatigue and a tendency to overeat (particularly carbohydrates) and oversleep in winter. A minority of individuals with SAD has the more common depressive symptoms of undereating and being sleepless. SAD tends to last about 5 months in those who live in the northern part of the U.S.

Seasonal changes affect many people's moods, regardless of gender and whether or not they have SAD. Simply being mildly depressed during the winter does not mean that one has SAD. Living in a northern country with long winter nights does not guarantee a higher risk for depression. Changes in light may not be the only contributor to SAD.

Causes

The causes of depression are not fully known. Most likely a combination of genetic, biologic, and environmental factors are at work.

Because depression runs in families, and has a strong genetic component, compelling evidence suggests that depression is a biologic phenomenon. Data from family, twin, adoption, and genetic studies have confirmed this. Studies have found that first-degree relatives of patients with depression are two to six times more likely to develop the problem than individuals without a family history.

Evidence supports the theory that depression has a biologic basis. The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain). These neurotransmitters regulate mood and associated behaviors. Scientists hope that by identifying the gene mutations that code the regulation of these neurotransmitters, they may eventually be able to predict which patients are most likely to respond to specific antidepressant drugs.

Serotonin. Perhaps the most important neurotransmitter in depression is serotonin. Among other functions, it is important for feelings of well-being. Imbalances in the brain’s serotonin levels can trigger depression and other mood disorders.
Other Neurotransmitters. Other neurotransmitters possibly involved in depression include acetylcholine and catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine, and epinephrine (also called adrenaline). Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety. Increased CRF concentrations appear to interact with serotonin and have been detected in patients with either depression or anxiety.

Endocrine glands release hormones into the bloodstream that are transported to various organs and tissues throughout the body. For instance, the pancreas secretes insulin, which allows the body to regulate levels of sugar in the blood. The thyroid gets instructions from the pituitary gland to secrete hormones that determine the pace of chemical activity in the body. The more hormone in the bloodstream, the faster the chemical activity; the less hormone, the slower the activity.

The degree to which these chemical messengers are disturbed is determined by other factors, such as light, structural abnormalities in the brain, sleep disorders, or genetic susceptibility. For example, researchers have identified a defect in the gene known as SERT, which regulates serotonin and has been linked to depression.

Reproductive Hormones. In women, the female hormones estrogen and progesterone most likely play a role in depression.

Women, regardless of nationality or socioeconomic level, have significantly higher rates of depression than men. The causes of such higher rates appear to be a mix of biologic and cultural factors.

Social and Economic Factors. The role that work, marriage, and children play in a woman's depression is complex. Many women feel that they must be everything to everyone and at the same time feel as if they are no one at all. Such a self-image is common and should be strongly considered as a major contributor to depression in many women, particularly those who work and have small children.

Hormonal Fluctuations and Life Stages. Extreme hormonal shifts can trigger emotional swings in all women. The role of hormones in depression is not clear, however, and is mostly based on observations of depression during specific stages in female development. Female hormones undoubtedly play some role in premenstrual dysphoria, postpartum depression, and SAD. These forms of depression recede or stop after menopause.

Early Puberty. Girls who go through puberty early (reaching the midpoint at 11 years or younger) are more likely to experience depression during adolescence than girls who mature later.

Premenopause. Premenopausal women ages 20 - 45 are most susceptible to depression, with 22% of this age group reporting symptoms of major depression. Specifically, premenstrual dysphoric disorder (severe depression before a period) affects an estimated 3 - 8% of women during their reproductive years. [For more information, see In-Depth Report # 79: Premenstrual syndrome.]

Perimenopause. Depression often occurs around menopause (the perimenopausal period), when, in addition to hormonal changes, other factors such as cultural pressures favoring young women, sudden recognition of aging, and sleeplessness are involved.

Postmenopause. Once women pass into the postmenopausal period, studies suggest that average depression scores are nearly as low as those in premenopausal women. In fact, many women report that after menopause, previous bouts of depression, particularly when caused by seasonal changes or premenopausal syndrome, recede or stop completely.

Premenstrual Dysphoric Disorder. The syndrome of severe depression, irritability, and tension before menstruation is known as premenstrual dysphoric disorder (PDD or PMDD), also called late-luteal dysphoric disorder. It affects an estimated 3 - 8% of women in their reproductive years. A diagnosis of PDD depends on having five or more standard symptoms of major depression that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward. PMDD has features of both anxiety and depression disorders, although experts increasingly believe it is a distinct disorder with specific biochemical abnormalities. [For more information, see In-Depth Report #79: Premenstrual disorder.]

Depression During Pregnancy. Pregnancy is certainly an occasion of great celebration for most women most of the time. However, emotions during that time are not always straightforward, and depression is a common (although most often a temporary) companion. Prenatal depression can affect a mother's sleep, physical activity, adherence to care, and appetite.

Miscarriage. Miscarriage poses a very high risk for depression, particularly in the first month after the loss. Older women with no previous successful pregnancies and those with a history of depression are at particular risk during this time. (Despite some concern that depression increases the risk for miscarriage in the first place, there is no evidence to support this.)

Postpartum Depression. Most new mothers experience weeping, irritability, and confusion for a few days following childbirth. Such symptoms, known as the "baby blues," are not considered signs of postpartum depression unless they persist in severe form nearly every day for more than 1 - 2 weeks.

Women are most likely to develop postpartum depression and other mental disorders in the first 3 months following delivery. (The risk is highest for first-time mothers, especially in the 10 - 19 days after delivery.) Other studies have reported that 8 - 20% of women have diagnosable postpartum depression within that 3-month period. In one study, 5% of these women had suicidal thoughts.

Studies have not found any association between a higher risk for postpartum depression in women and the following:

Educational level
Gender of the child
Whether or not the woman breast-feeds
Whether or not the pregnancy was planned
Whether the delivery was vaginal or cesarean

The rapid decline of reproductive hormones that accompany childbirth is likely to play the major role in postpartum depression in susceptible women. Fluctuating thyroid hormones can also contribute to depression. Studies suggest that women who are more sensitive to hormone fluctuations are at greater risk for postpartum depression if they have one or more of the following conditions:

A history of prior depressive episodes
A family history of mood disorders
Stressful life events (such as being a new mother and having an infant with medical problems)
Lack of social support or feeling as if it is lacking

Depressed children often suffer in silence, and depression may be evident only from reports of problems in school. It is also often difficult for adults to believe that children can be chronically depressed. Symptoms for depression in children often differ from those in adults and may include the following:

An inability to enjoy favorite activities
Persistent sadness
Increased irritability
Complaints of physical problems, such as headaches and stomachaches
Poor performance in school
Persistent boredom
Low energy
Poor concentration
Changes in eating and/or sleeping patterns
A greater tendency to bully others -- anxious children are more often bullied.

Risk Factors for Depression in Children and Adolescents. Depression can occur in children of all ages, including preschoolers, although adolescents have the highest risk (about 20%). Risk factors for depression in young people include having parents, particularly mothers with depression. Early negative experiences and exposure to stress, neglect, or abuse also pose a risk for depression. Sometimes depression develops after a physical illness. In adolescents, feeling alienated from parents is a strong predictor for depression.

Outlook for Future Emotional Problems. Adolescents who have depression are at significantly higher risk for substance abuse, recurring depression, and other emotional problems (such as bipolar disorder) in adulthood.

Risk for Suicide in Adolescents. Suicide is the third most common cause of death among adolescents, and is one of the most devastating events than can happen to a family. Suicide is most commonly associated with depression in young people but it is also linked with anxiety, psychosis, substance abuse, or impulsivity. More girls attempt suicide but more boys succeed, most often because they choose guns or violent methods while girls tend to overdose, which is more treatable. Nevertheless, attempts are major risk factors for a later suicide. Any expression of suicidal intent should be treated very seriously.

The following are danger signs in young people:

Withdrawal from friends
Sudden decrease in school performance
Loss of interest in activities that were previously pleasurable
Unusual irritability
Unusual changes in sleep or eating habits

Risk factors for suicide include a history of neglect or abuse, history of deliberate self-harm, a family member who committed suicide (nearly always one who shared a common mood disorder), access to firearms, and living in communities where there have been recent outbreaks of suicide in young people. A romantic break-up is often the trigger for a suicidal attempt in teenagers. Feeling connected with parents and family protected young people with depression in one study, regardless of gender or ethnicity.

Adolescents may fail to seek help for suicidal thoughts for the following reasons:

They believe nothing would help
They are reluctant to tell anyone they had problems
They think it is a sign of weakness to seek help
They do not know where to go

Parents should not hesitate to seek professional help for their children if they suspect they are thinking about killing themselves. This is a medical emergency and requires immediate treatment.

Behavioral therapies and antidepressants are promising treatments for preventing suicide but need study. There has been a decline in adolescent suicides over the past decade, which some experts attribute to the increased use of antidepressants in this population. However, recent evidence has indicated that antidepressants can also raise the risk for suicidality (suicidal thoughts and behavior) in some people. Children, adolescents, and young adults who are prescribed antidepressant medication should be carefully monitored by both their parents and doctor, especially during the first few months of treatment, for any worsening of depression symptoms or changes in behavior. [See Suicide Risk and Antidepressant Medications in Medication section.]

Although depression in the elderly is very common, the aging process itself is unlikely to be the cause in most cases. An Italian study, for example, indicated that the very old (people who lived beyond 90 years of age) were no more likely to be depressed than younger adults. (The rate was 10% in both groups.) Studies on the cause or extent of depression in the elderly are not clear.

The severity of depression in elderly patients is strongly associated with poor health and less ability to function. In one study of older adults undergoing rehabilitation, half of whom were depressed, as their function improved so did their mood.

Anyone who experiences cumulative negative life events, physical illness, the death of a loved one, impaired functioning, or loss of independence can become deeply depressed. The elderly are at highest risk for such events.

Diagnosing Depression in the Elderly. Because of the complex relationship between depression, drug interactions, and serious physical illness in the elderly, an accurate diagnosis in this group is important but not always straightforward. The characteristic symptoms of depression are not always present or readily apparent in older people:

Some older people may be aware of their depression but believe that nothing can be done about it.
Many elderly people who are depressed may report only physical symptoms (aches and pains) or other mood states (confusion, agitation, anxiety, and irritability) related to depression rather than depression itself.
Often they are unable or unwilling to express their feelings or are even unaware that they are depressed.
Their symptoms are often ignored or confused with other ailments common in the elderly, including Parkinson's or Alzheimer's disease, dementia, thyroid disorders, arthritis, stroke, cancer, heart disease, and other chronic conditions.
Depression is also a side effect of many drugs that are commonly prescribed for the elderly. It is often very difficult, then, to determine if the patient's depression is a psychologic reaction to the illness, caused by the disease itself, or completely independent from the medical condition. Both physical and emotional conditions should be considered in making a diagnosis in older people.

Many studies suggest strong associations between even mild depression and poorer quality of life as well as a shorter lifespan.

Risk for Suicide in the Elderly. Suicide in the elderly is the third-leading cause of death related to injury. Men account for 81% of these suicides, with divorced or widowed men at highest risk.

Effects of Depression on the Ability to Function. Even mild depressive symptoms in people aged 65 and above are associated with a higher risk of becoming disabled and having a lower chance of recovery.

Heart Disease and Heart Attacks. Depression increases the severity of a heart attack and may even impair a patient's response to medication for heart disease. Although people with heart disease may certainly become depressed, this does not explain entirely the link between the two problems. Data suggest that depression itself may be a true risk factor for heart disease as well as its increased severity. A number of studies indicate that depression has biologic effects on the heart, including a higher risk for blood clotting, changes in heart rate, and impaired blood flow to the heart (particularly in response to mental stress). The more severe the depression, the more dangerous to the health, although even mild depression, including feelings of hopelessness, experienced over many years, may harm the heart, even in people with no early signs of heart disease.

Mental Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia. Depression may be a predictor or even a cause of Alzheimer's disease. Brain scans in the elderly, for example, have reported greater atrophy in the brains of depressed individuals than in those of nondepressed ones.

Risk Factors

According to a major surveys, more than 13% of Americans have major depression disorder over the course of their lifetimes. Furthermore, an estimated 18 million Americans experience major depression each year. Depression is second only to high blood pressure as a chronic condition encountered by primary care doctors. Depression is an illness that can afflict anyone, regardless of age, race, class, or gender. A third of all depressed people consider suicide, and 9% attempt it.

Depression in Women. At any given time, 5 - 9% of women are depressed, compared to 1 - 3% of men. In one study, nearly half of all women surveyed had experienced depression at some point in their lives and over half of those who suffered from it had sought treatment. Women are also more apt to have multiple types of depression (dysthymia and major depression). [For more information, see Depression in Women.]

Depression in Men. Depression is not rare in men. In fact, prepubescent boys are more likely than girls of the same age to be depressed. Older men are also at much higher risk for suicide and, as with women, they are at risk for health complications of depression. Some evidence suggests that men are more apt than women to mask their depression by using alcohol, which may result in a lower reported (but not actual) incidence of depression in men. Some experts suggest that men with depression might be identified with the following indicators:

Low tolerance to stress
Behaviors such as "acting out" and being impulsive
A history of alcohol or substance abuse
A family history of depression, alcohol abuse, or suicide

Depression is less reported in the male population, but this may be caused by male tendency to mask emotional disorders with behavior such as alcohol abuse.

Depression in Children and Adolescents. Children ages 12 - 16 are at high risk for depression. Studies suggest that 3 – 5% of children and adolescents suffer from depression, and 10 – 15% have some depressive symptoms. Depression before puberty is more likely to occur in boys and after puberty in girls.

Depression in Adults. Surveys indicate that depression usually begins around the age of 30, although people do not generally seek treatment until they are about 33 years old. Statistics also suggest that depression is becoming more common among middle-aged people ages 45 - 64. According to a 2005 survey, middle-aged adults have the highest lifetime risk for depression.

Depression in the Elderly. Studies suggest that 5 – 14% of the elderly population suffer from some form of depression. In addition, the elderly are highly vulnerable to suicide. Elderly people comprise 13% of the U.S. population but account for 18% of all suicide deaths.

The role of society and economics has specific implications for women. [See Depression in Women.] Being in a low socioeconomic group is a major risk factor for depression in anyone. Money, of course, allows greater access to good medical care, but this factor does not fully explain the higher rates of depression in impoverished people. People at any income level are likely to be depressed if they have poor health and are socially isolated. Some studies suggest that Western cultural attitudes that link income to social status may play a significant role in the connection between poverty and depression:

In one British study, actual poverty or unemployment increased the duration of any existing depression, but it did not appear to play any important causal role. Feelings of financial insecurity, however, both caused and prolonged depression.
Another study reported that Mexican adults who immigrated to America had half the psychiatric illnesses as did Mexican-Americans born in the U.S., regardless of their income. But the longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional influences of Mexican culture and social ties appeared to protect newly arrived immigrants from mental illness, even when they were poor. Eventually, however, the consequences of Americanization added to poverty and led to feelings of alienation and inferiority.

Depression in family members increases the risk for depression in other family members. Studies report that depression for even 1 - 2 months in a mother increases the risk for depression in her children. The more severe the maternal depression, the higher the risk for depression in the children. In a perpetuating cycle, being depressed as a child increases the risk for depression during adulthood. In such cases, genetic or environmental factors or both may be responsible. Spouses of partners with depression are themselves at higher risk for depression.

Patients who have had serious bouts of depression usually cite a stressful life event as the precipitating factor for their illness. Adverse events during childhood pose a higher risk for depression in adulthood. In one study, parental divorce, physical abuse, and frightening experiences were particularly associated with onset of depression in adulthood. Only divorce was associated with recurrence, however.

Adverse events in adulthood also trigger depression. Losing a spouse through divorce or death is a major risk factor for depression in anyone. In fact, recent loss of a loved one is the most frequently reported precipitant of acute depression. All major (and even minor) losses, however, cause grief reactions. People who develop acute or chronic depression after a loss may have predisposing factors, including genetic or biologic ones, which make them more vulnerable. The existence or absence of a strong social network of family, friends, or both also has a major positive or negative effect, respectively, on recovery. Most people are able to cope with the emotional pain and eventually move beyond it without becoming chronically depressed. [See Ruling out Grief and Loneliness in the diagnosis section of this report.]

Traumatic events such as abuse or even natural disasters can cause severe immediate or delayed depression from which recovery takes a long time.

Severe or Chronic Medical Conditions. Any chronic or serious illness that is life-threatening or out of a person's control can lead to depression.

Thyroid Disease. Hypothyroidism (a condition caused when the thyroid gland does not produce enough hormone) can cause depression. However, hypothyroidism may also be misdiagnosed as depression and go undetected.

Chronic Pain Conditions. Studies have reported a strong association between depression and headaches, including chronic tension-type and migraine. Some experts believe that a syndrome of migraine headaches (and also possibly tension-type), anxiety, and depression is caused by common factors, such as abnormalities in chemical messengers, particularly dopamine or serotonin. Fibromyalgia and other chronic pain syndromes are also associated with depression.

Stroke and Other Neurological Conditions. Having a stroke increases the risk of developing depression. Also, patients with Parkinson's disease, spinal cord injuries, and other similar problems that impair movement or thinking are associated with depression.

Heart Failure. Patients with heart failure or patients who have suffered a heart attack may also suffer from depression.

A number of drugs taken for chronic problems cause depression. Among them are pain relievers for arthritis, cholesterol-lowering drugs, medications for high blood pressure and heart problems, and bronchodilators used for asthma and other lung disorders.

There is a significant association between cigarette smoking and a susceptibility to depression. People who are prone to depression face a 25% chance of becoming depressed when they quit smoking, and this increased risk persists for at least 6 months. What's more, depressed smokers are unlikely to stop smoking. Only about 6% remain smoke-free after a year. Smokers with a history of depression are not encouraged to continue smoking, but rather to keep a close watch on recurrence of depressive symptoms if they do stop smoking. The antidepressant bupropion (Wellbutrin), which is approved for helping people quit smoking (marketed under the name Zyban), is proving to be very useful in helping smokers to quit.

Chronic depression is a frequent companion to anxiety disorders. In one study, up to 96% of patients with depressive disorders experienced concurrent anxiety. More than two-thirds of people with obsessive-compulsive disorder, a common anxiety disorder, also suffer from depression.

Some evidence suggests that certain personality styles, which include an intense need for close relationships and concern for disapproval or need for control, pose a high risk for depression, particularly after an adverse life event. In line with these findings, the following specific personality disorders have been associated not only to a first episode of depression, but also to relapses:

A person with borderline personality disorder acts impulsively and has a poor self-image and unstable relationships. In one study, patients with borderline personality disorder and major depression were more likely than those with either condition alone to plan and attempt suicide.
An individual with an avoidant personality avoids strangers and unfamiliar situations.

(Personality disorders, as opposed to emotional disorders, are those with abnormal behavioral patterns rather than abnormal emotions.)

Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia. Although stress and depression are major causes of insomnia, insomnia may also increase the activity of the hormones and pathways in the brain that can produce emotional problems. Even modest alterations in waking and sleeping patterns can have significant effects on a person's mood. Persistent insomnia may even predict the future development of emotional disorders. Some experts think that some psychiatric disorders can be prevented by early recognition and treatment of insomnia.

Seasonal affective disorder (SAD) affects about one in 20 adults. About 80% of people who suffer from SAD are women. People who live in the north are more apt to experience SAD than people who live in southern latitudes.

Complications of Depression

Depression is often chronic, with episodes of recurrence and improvement. About one-third of patients with a single episode of major depression will have another episode within 1 year after discontinuing treatment, and more than 50% will have a recurrence at some point in their lives. Depression is more likely to recur if the first episode was severe or prolonged, or if there have been recurrences. To date, even newer antidepressants have failed to achieve permanent remission in most patients with major depression, although the standard medications are very effective in treating and preventing acute episodes.

About 90% of suicides are due to treatable disorders, most commonly depression or substance abuse. People with depression have up to a 15% risk for suicide, with the highest risk in patients who are hospitalized for depression. Some studies indicate that atypical depression poses a higher risk for suicide than typical depression and that dysthymia may pose a higher risk than episodic major depressive disorder. Depressed men are more likely to commit suicide than depressed women. Around the world, suicide is most common in men older than 60. Suicidal preoccupation or threats of suicide should always be treated seriously in anyone, however. [See Depression in the Elderly or Depression in Children in this report.]

Major depression in the elderly or in people with serious illness seems to reduce their survival rates, even independently of any accompanying illness. Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity.

Effect on Heart Disease and Other Age-Related Problems. Many studies report strong associations between depression and a worse and even shorter old age. Depression is also associated with mental decline in older people.

Studies are now showing that depression may contribute to poor outcomes for patients with heart disease.

Obesity. Both obesity and depression are increasing in Americans. Adolescents who are depressed have a high risk for obesity. Conversely, obese people are about 25% more likely than non-obese people to develop depression or other mood disorders. The conditions may have common risk factors. For example, being in a lower social and economic group increases the risk for both obesity and depression. Low physical activity may also be a common factor.

Increasing Sensations of Pain. Depression coincides with increased pain in people with conditions such as those arthritis or fibromyalgia.

Cancer. The relationship between depression and cancer has been explored for years with only a few clear-cut associations. Certainly depression and anxiety can have a profound impact on quality of life in cancer patients.

Effects of Parental Depression on Children. Depression in parents can have profound effects on their children and may increase the risk for childhood depression.

Effects on Marriage. In one survey, nearly half of people who suffered from psychiatric disorders before or during their first marriage were divorced, compared to a divorce rate of 36% in those who never suffered from emotional disorders. Spouses of partners with depression are themselves at higher risk for depression.

Effect on Work. Depression is well-known to adversely affect a person's work life. It significantly increases the risk for unemployment and lower income. Nearly half of the nation's excess lost productive time (in most cases because of reduced performance at work) may be a result of depression. Workers with depression also lose significantly more time due to ill health than non-depressed workers. Such lost time is estimated to cost the country billions of dollars each year.

Alcohol and Drug Abuse. About 14% of people with major depression also have an alcohol use disorder and 5% have drug abuse problems. Studies on the connections between alcohol dependence and depression have still not resolved whether one causes the other or if they both share some common biologic cause.

Smoking. Depression is a well-known risk factor for smoking, and 26% of people with major depression are nicotine dependent. Nicotine may stimulate receptors in the brain that improve mood in certain people with genetically induced depression.

Diagnosis

Most people who are depressed do not seek psychiatric help and must rely on their family doctor. Unfortunately, it is often difficult for a primary care doctor to recognize the problem if the patient does not bring it up directly.

Patients themselves may be unable to sense or admit their own depression. In one study, although 21% of patients who visited their family doctors were depressed, only 1% described their problem as depression.

Depression can also be confused with other medical illnesses. Weight loss and fatigue, for example, accompany many conditions, some serious, but they can also occur with depression.

Although not all patients who visit their doctor should be screened for depression, individuals who have certain factors might ask their doctor if they should be screened for depression. For example, the following people may be at higher risk and therefore warrant a screening test:

People with a family or personal history of depression
Patients with multiple medical problems
Patients with physical symptoms that have no clear medical cause
Patients with chronic pain
Individuals who visit their doctor more frequently than expected

A mental health specialist, such as a psychiatrist, social worker, or psychologist, is the best source for a diagnosis of depression. Such health professionals may administer a screening test such as the Beck Depression Inventory or the Hamilton Rating Scale, both of which consist of about 20 questions that assess the individual for depression. Studies are finding that even computerized phone interviews are valuable as screening tools for depression. However, most mental health professionals generally diagnose depression based on symptoms and other criteria.

Specific ethnic groups may present different symptoms of depression. People from non-Western countries are more apt to report physical symptoms (such as headache, constipation, weakness, or back pain) related to the depression, rather than mood-related symptoms.

Grief. The symptoms of grief (bereavement) and depression have much in common; indeed, it may be difficult to separate the two. Grief, however, is considered to be a healthy and important emotional response for dealing with loss, and it generally follows a characteristic path:

Grief normally has a limited duration. In people without any co-existing emotional disorder, bereavement usually lasts between 3 - 6 months.
The grieving person typically endures a succession of emotions that include shock and denial, loneliness, despair, social alienation, and anger.
The recovery period following this process, during which the individual becomes re-involved with life, takes about the same amount of time as the bereavement cycle.

If the grief is still severe after this period, however, it may affect a person's health or increase the risk for on-going depression. Some experts suggest that such a severe persistent grieving state be categorized as a separate psychologic diagnosis, termed complicated grief disorder, which would be related to post-traumatic stress syndrome and require special treatment.

Loneliness. Like grief, loneliness is a condition that may often be mistaken for depression. In fact, while loneliness and depression often go hand in hand, some researchers believe that some people with loneliness may be effectively treated for depression. Of course, every person feels loneliness now and then. Debilitating loneliness, however, is often characterized by misery, a feeling of hollowness, unrealistic expectations for one's life, and feeling removed from others. Shy people may be more prone to loneliness. Psychotherapy of various kinds may help people address and allay loneliness.

Treatment

Depression is a treatable illness, with many therapeutic options available. Increasingly, professionals are viewing major depression as a chronic illness (the condition nearly always returns when treatment is stopped). Therefore, medical intervention and help must be ongoing.

Patients with chronic depression have a number of options, including psychotherapy, antidepressants, or both. In general, the treatment choice depends on the degree and type of depression and other accompanying conditions. It also may depend on age, pregnancy status, or other individual factors.

Unfortunately, many Americans with major depression receive either inadequate treatment or no treatment at all. Reasons may include treatment by providers who may not have sufficient information or training on dosages or specific drugs that would be best suited for individual cases, lack of recognition of depression symptoms by providers, poor access to health care services, lack of health insurance, and poor compliance with medications.

Patients with Major Depression. Numerous studies support a combination of cognitive behavioral therapy (CBT) plus antidepressants, typically a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI). Although some people may feel better after taking antidepressants for a few weeks, most people need to take medication for at least 6 - 12 months to ensure a full response. Research indicates that patients respond better to medications when drug therapy is combined with CBT. Exercise is also important in helping relieve depressive symptoms.

For patients who are not helped by SSRIs or SNRIs, other types of antidepressants are available. Sometimes an atypical antipsychotic drug may be given in combination with an antidepressant for patients with severe major depressive disorder.

Brain stimulation techniques, such as electroconvulsive therapy (ECT) and vagus nerve stimulation, are also options. In recent years, experimental procedures, such as repetitive transcranial magnetic stimulation, have also been found to help in some cases of treatment-resistant depression. Researchers are also investigating new types of drugs (such as ketamine), which may provide a rapid, if temporary, improvement for these patients. In general, the more treatment strategies that patients need, the less likely they are to recover completely from depression.

Patients with Minor Depression. Patients with minor depression (fewer than five symptoms that persist for fewer than 2 years) may respond well to watchful waiting to see if antidepressants are necessary. Some studies indicate that antidepressants do not work that well for mild depression. Counseling or cognitive behavioral therapy may be helpful, as is regular exercise.

Patients with Depression and Other Psychiatric Problems. Other psychiatric problems often coexist with depression. If patients also suffer from anxiety, treating the depression first often relieves both problems. More severe psychiatric problems, such as bipolar disorder or schizophrenia, require specialized treatments.

Patients with Depression and Medical Conditions. Depression can worsen many medical conditions and may even increase mortality rates from some disorders, such as heart attack and stroke. Depression, then, should be aggressively treated in anyone with a serious medical problem.

Patients with Depression and Substance Abuse Problems. Treating depression in patients who abuse alcohol or drugs is important and can sometimes help patients quit. However, absence from substance abuse is considered essential for adequate treatment of depression.

Most people with depression can be treated in an office setting by a psychiatrist or other therapist. Infrequently, the level of dysfunction may be serious enough to warrant hospitalization to provide protection from further deterioration or self-harm.

Health professionals who can prescribe antidepressants include:

Doctors, including psychiatrists
Some nurse clinicians

Although other mental health professionals cannot prescribe drugs, most therapists have arrangements with a psychiatrist for providing medications to their patients. In general, mental health professionals are categorized by their training:

Psychoanalysts tend to have a degree in psychiatry, psychology, or social work as well as several years of training at a psychoanalytic institute.
Psychologists have received a Ph.D, including an internship in a mental healthcare facility.
A clinical social worker has a master's degree and 2 years of supervised experience in mental health and human services.
Advanced-practice psychiatric nurses have a master's degree and can provide therapeutic services.

Tips for Selecting a Therapist:

Patients can locate a mental health professional in their area by asking their doctor for a referral or by contacting a mental health organization. [See Resources.]
The patient should describe problems briefly but specifically over the phone to any prospective therapist to get a sense of whether he or she will suit the patient's needs.
An advanced degree does not necessarily guarantee quality therapy. The patient's belief in their health care provider may be the most important component in recovery.
Patients should not be shy about considering a change in their therapist if they lack confidence in their current one.

Although a mother's depression during and after pregnancy can have serious effects on her child, researchers are still trying to determine the best methods for preventing and treating pregnancy-related depression.

The use of antidepressants during pregnancy is controversial, especially for women with major depression who regularly take antidepressant medication. Most doctors advise women to avoid, if possible, any medications during pregnancy and nursing. But, women with depression who stop taking antidepressants during pregnancy may be likely to have a relapse of depression. Women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors.

Some research suggests that certain serotonin reuptake inhibitors (SSRIs) may increase risks for the fetus. The strongest evidence concerns the SSRI paroxetine (Paxil), which can cause major birth defects -- including heart abnormalities -- if taken during the first trimester of pregnancy. In 2006, the American College of Obstetricians and Gynecologists recommended that doctors should not prescribe paroxetine to women who are pregnant or planning on becoming pregnant.

Other research indicates that first-trimester use of SSRIs may increase the risk for rare skull and neural tube defects. Venlafaxine (Effexor), a dual inhibitor antidepressant, has been associated with birth complications when taken during the last trimester. In addition, some studies have shown that babies may experience withdrawal symptoms if their mothers take SSRIs late in pregnancy. However, the overall evidence indicates that there is a very low overall risk for antidepressant-associated birth defects and problems. Still, women should discuss all potential risks with their doctors.

In terms of non-drug treatment of postpartum depression, a review of 15 clinical trials suggested that postpartum depression is best treated by intensive and individualized psychotherapy within a month after a woman gives birth. The researchers found that women are too busy in the weeks before birth to attend prenatal classes that focus on preventing postpartum depression.

Some experts recommend only psychotherapy or attention intervention for elderly patients with mild depression. In many older patients, a regular exercise program may be sufficient to improve mood. Ideally, elderly people with more serious depression should be treated with a combination of psychotherapy and antidepressants on an ongoing basis, even after their depressive symptoms are relieved.

The use of antidepressants in the elderly is problematic:

Tricyclics are as effective as, and less expensive than, SSRIs, but they have more side effects. Specifically, they pose a higher risk for adverse effects on the heart and possibly the lungs. (The older tricyclics, such as amitriptyline and imipramine, have other severe side effects in older adults.)
SSRIs have fewer side effects than tricyclics. However, SSRIs may not pose any lower risk for falls than the older tricyclic antidepressants. In addition, researchers are investigating whether SSRIs are associated with an increased rate of osteoporosis (“thin bones”) and fractures in older adults.

About 2% of American primary school-age children and 4 - 8% of adolescents suffer from depression. Studies suggest that when children or adolescents are treated, up to 80% recover. Still, 25 - 50% of these young people have a recurrence of depression within 2 years of their first episode of depression.

It is important to recognize that childhood depression differs from adult depression and that children may respond differently than adults to antidepressant medication. These variances are due to childhood brain development processes as well as age-related differences in drug metabolism. Children may experience medication side effects not seen in adults, and some antidepressants that are effective for adults may not work for children.

Mild-to-Moderate Depression. The pediatrician may want to monitor a child with mild depression for 6 - 8 weeks before deciding whether to prescribe psychotherapy, antidepressant medication, or a referral to a mental health professional. Once medication has been started, the doctor will decide if the dosage needs to be increased after another 6 - 8 weeks. Medication may need to be continued for 1 year after the symptoms have resolved, and the doctor should continue to monitor the child on a monthly basis for 6 months after full remission of depression. For psychotherapy, cognitive therapy may be the best approach for children and adolescents with depression. Some studies suggest that other types of psychotherapy, such as family therapy and supportive therapy, can also be very effective.

Severe Depression. The American Academy of Child and Adolescent Psychiatry recommends an SSRI antidepressant for children and adolescents with very severe depression that does not respond to psychotherapy. Tricyclic antidepressants do not tend to help adolescents and children and these drugs have many side effects. MAOIs are also not commonly prescribed.

Many SSRIs appear to be safe and effective, but at this time fluoxetine (Prozac) is the only one approved for children over age 7 and for adolescents. The FDA strongly advises against the use of specific SSRIs, such as paroxetine (Paxil), due to concerns about an increased risk for suicidal behavior as well as the lack of any evidence supporting the drug's efficacy in pediatric patients. On an encouraging note, a 2007 review in the Journal of the American Medical Association indicated that the overall benefits of antidepressants for children and adolescents appear to be much greater than the risks for suicidal behavior. Still, the study found that antidepressants have only modest benefits for major depressive disorder, which underlines the importance of adjunctive psychotherapy.

For optimal results, SSRIs should be combined with either cognitive-behavioral or interpersonal psychotherapies. A study of adolescents with depression reported that combination treatment with fluoxetine and cognitive behavioral therapy was more effective than either treatment alone.

Due to potential suicide risks, children and adolescents should be monitored regularly during the initial months of antidepressant treatment. [For more detailed information, see Suicide Risk and Antidepressant Medications.]

Antidepressants and Drug Treatment Guidelines

Major classes of antidepressants include:

Selective serotonin-reuptake inhibitors (SSRIs). These have become the standard antidepressants. They target the brain chemical (neurotransmitter) serotonin. They are effective and have very moderate side effects. Some may be beneficial in treating anxiety and certain subtypes of depressive disorders unresponsive to previous drugs, including premenstrual dysphoric disorder and seasonal affective disorder, atypical depression, and recurrent brief depression.
Other neurotransmitter inhibitors. These drugs target neurotransmitters other than or in addition to serotonin, such as norepinephrine. Many are proving to be effective in patients who do not respond to standard antidepressants or in specific patients, such as smokers who want to quit or patients with chronic pain.
Tricyclic antidepressants (TCAs). These drugs are effective but can have severe adverse effects, particularly in older people.
Monoamine oxidase inhibitors (MAOIs). These drugs include newer selective MAOIs. MAOIs are the most effective antidepressants for atypical depression, but have some severe side effects and require restrictive dietary rules.
St. John's wort and other herbal remedies are included in the Lifestyle section of this report.

Approach and Duration of Initial Treatment. The guidelines for the duration of an initial antidepressant regimen is as follows:

Patients should start at a low dose, which is increased over a period of 5 - 10 days.
Patients should see their doctor every 1- 2 weeks until substantial improvement occurs. It may take 4 - 8 weeks before a patient experiences the effects of any antidepressant.
Side effects usually diminish within 1 - 4 weeks. (Exceptions may be weight gain and sexual dysfunction.)
If no improvement occurs, an alternative drug may be tried. More than 80% of patients respond to some antidepressant, although specific drugs are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. In general, the fewer drug treatment strategies required, the better a patient’s chances of recovering completely from depression. Patients who become symptom-free have the best chance for complete recovery compared to patients whose symptoms merely improve.
In general, patients should continue taking antidepressants for at least 6 months after symptom relief to help prevent relapse. (Patients who improve within 2 weeks of taking medications may not require lengthy treatment.)

Treating Recurrence. Recurrence of depression is very common. About a third of patients will relapse after a first episode within a year of ending treatment, and more than half will experience a recurring bout of depression at some point during their lives. Among those at highest risk for early relapse and who may require ongoing antidepressants are:

Patients with at least two episodes of major depression or major depression that lasts for 2 years or longer before initial treatment.
Patients who continue to have low-level depression for 7 months after starting antidepressant treatments.

Patients may need maintenance therapy. Experts disagree, however, on the optimal length or the appropriate dosage of maintenance therapy. Some patients may need to stay on antidepressants for 1 - 2 years -- or even indefinitely. Some experts recommend withdrawing from medication after a year. (This should be done gradually, over 2 - 3 months.) If depression recurs, the patient should go back on the antidepressants.

There is no risk for addiction with current antidepressants, and many of the common antidepressants, including most standard SSRIs, have been proven safe when taken for a number of years.

Common Side Effects of Most Antidepressants. No matter how well a drug treats depression, the ability of the patient to tolerate its side effects strongly influences their compliance with therapy. Lack of compliance is probably the major barrier to success. Side effects can be avoided or moderated if any regimen is started at low doses and built up over time. Although specific side effects are discussed under individual drugs, there are a few that are common to many of them:

Sexual dysfunction is a common side effect of many of the standard antidepressants and some of the newer drugs. These side effects can be particularly distressing for patients on maintenance treatment who otherwise feel well. Some of the newer antidepressants, such as bupropion, may be effective alternatives without as high a risk for this problem. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants. It does not heighten sexual interest, however.
An increased risk of oral health problems caused by dry mouth is associated with long-term use of most antidepressants. Patients can increase salivation by chewing gum, taking vitamin C tablets, using saliva substitutes, and rinsing the mouth frequently.
Virtually all antidepressants have complicated interactions with other drugs; some are very important. Patients should inform the doctor of any drugs they are taking, including over-the-counter medications and herbal remedies.
Nearly all antidepressants are metabolized in the liver, so anyone with liver abnormalities should use them with caution.
Abrupt withdrawal from many antidepressants can produce severe side effects; no antidepressant should be stopped abruptly without consultation with a doctor.

In recent years, there has been concern that SSRI antidepressants may increase the risk for suicidal behavior. Of particular concern is a greater risk for suicide in young people taking these medications. While depression is itself the major risk factor for suicide, and antidepressant medication may revitalize suicidal attempts in patients who were too despondent before treatment to make the effort, evidence suggests that in some cases the medication itself can cause suicidal behavior. One specific SSRI, paroxetine (Paxil), has been definitely linked with suicidal behavioral risk in adults ages 18 - 30. In May 2006, the drug’s manufacturer warned doctors that all patients, and particularly young adults, should be carefully monitored during paroxetine therapy.

The U.S. Food and Drug Administration (FDA) has been conducting in-depth research on suicide risk and antidepressant medications. In October 2004, after careful review of scientific evidence, the FDA issued a public health advisory instructing drug manufacturers to include a "black box" warning explaining the association between antidepressant use and increased risk for suicidality (suicidal thoughts and behavior) in children and adolescents. In May 2007, the FDA proposed that the labels of antidepressant medications should include additional warnings about the risk of suicidal thoughts and behavior in young adults (ages 18 - 24) during the first 1 - 2 months of treatment. The FDA also notes there is a decreased risk of suicidality for adults age 65 years and older taking antidepressants.

The FDA based its recommendations for children and adolescents on a review of 24 clinical trials of nine antidepressant drugs. These trials enrolled over 4,400 pediatric patients and tested the safety and efficacy of SSRIs as well as other classes of antidepressants. The data suggested a greater risk for suicidality within the first few months of treatment. The average risk was minimal. Children and adolescents treated with these drugs had a 4% risk for suicidality compared with 2% for patients who received placebo. No patients in these studies actually committed suicide.

Based on these findings, the FDA recommends that caregivers monitor children being treated with antidepressants for sudden behavioral changes, and immediately notify their doctor if such changes occur. These behavioral signs include:

Agitation
Irritability
Anxiety
Panic attacks
Insomnia
Aggressiveness
Impulsivity
Hyperactivity in actions and speech
Worsening of depression
Increased thoughts of suicide

The FDA’s guidelines for medication usage recommend that patients see their doctor regularly after initiating drug treatment. The recommended schedule is:

Once per week for 4 weeks (1st month)
Every 2 weeks for the next month (2nd month)
At the end of week 12 following the start of drug treatment (3rd month)
More frequently if changes in mood or behavior occur
Patients should also be closely monitored if their drug dosage is changed.

Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Selective serotonin-reuptake inhibitors (SSRIs) are now the first-line treatment of major depression. They work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro). There are no significant differences among SSRI brands in effectiveness for treating major depressive disorder, although individual drugs may have different side effects or benefits for specific patients. At this time, fluoxetine is the only one of these drugs to be approved for children over age 7 and adolescents.

Because they act specifically on serotonin, SSRIs have fewer side effects than older antidepressants, which have more widespread effects in the body.

Candidates for SSRIs. SSRIs appear to help people with the following conditions:

Mild to moderately severe major depression
Seasonal affective disorder
Dysthymia
Severe premenstrual syndrome and premenstrual dysphoric disorder (PMDD) -- a repackaged form of fluoxetine (Sarafem) is the first SSRI specifically FDA-approved for PMDD. Other SSRIs and newer antidepressants are also proving to be effective
Anxiety disorders
Bulimia
Impulsive and aggressive behaviors in psychiatric patients and in people with no mental health problems

Duration of Effectiveness and Use. SSRIs take, on average, 2 - 4 weeks to be effective in most adults. They may take even longer, up to 12 weeks, in the elderly and in those with dysthymia. By 14 weeks, depression should be in remission in everyone who responds to the drugs. Unfortunately, recurrence is common once the drugs are stopped. Studies indicate that the standard SSRIs are generally safe, although it is still unclear which patients would most benefit from on-going medication. Some doctors recommend withdrawing from medication after a year. If depression recurs, then the patient should go back on the antidepressant.

Side Effects of SSRIs. Side effects may include:

Nausea and gastrointestinal (GI) symptoms usually wear off over time.
Agitation, insomnia, mild tremor, and impulsivity occur in 10 - 20% of people who take SSRIs. These symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both.
Drowsiness affects about 20% of SSRI-treated patients. Newer SSRIs, such as escitalopram (Lexapro), may have fewer of these adverse effects.
Dry mouth is a common side effect.
Patients may lack motivation, feel tired, be confused, and experience mental dullness, but this side effect is fairly rare.
Headache and flu-like symptoms may occur.
Heart palpitations and chest pain may occur.
Weight gain varies depending on the SSRI. For example, in one study patients who took paroxetine (Paxil) experienced five times the weight gain as those who took citalopram (Celexa). Patients should be encouraged to maintain a low-calorie diet and to exercise. They should be aware that some of the weight-loss medications, notably sibutramine (Meridia), can have serious interactions with SSRIs.
Sexual side effects include delayed or loss of orgasm and low sexual drive. They are a well-known side effect of SSRIs. Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. Some of the newer SSRIs or other antidepressants may cause less severe impairment of sexual function.
Paroxetine (Paxil) may cause birth defects if taken during the first 3 months of pregnancy. Most reported defects have been heart-related. The most common heart abnormalities are ventricular septal defects, which are holes in the muscular wall that separate the main pumping chambers of the heart. Venlafaxine (Effexor) has also been associated with birth defects. Still, recent research suggests that most types of SSRI-associated birth defects are rare and the overall risks are low. Pregnant women who are being treated for major depression should not stop taking antidepressants without first talking to their doctors. [For more information on antidepressant treatment guidelines during pregnancy, see Treating Depression During and After Pregnancy in Treatment section.]

Drug Interactions. SSRIs can interact with other antidepressants such as tricyclics and, in particular, monoamine oxidase inhibitors (MAOIs). SSRIs should never be taken in combination with an MAOI or within 2 weeks after discontinuing MAOI treatment. Other serious interactions have occurred with meperidine (Demerol) and illegal substances (such as LSD, cocaine, or ecstasy). People who take SSRIs may drink alcohol in moderation, although the combination may compound any drowsiness experienced with SSRIs, and some SSRIs increase the effects of alcohol.

Withdrawal Symptoms. Cognitive problems, sleep disturbances, increase in depressive symptoms, and electric shock-like symptoms have been known to occur with sudden discontinuation of SSRIs. The symptoms are more likely to occur with antidepressants with shorter half-lives as compared with fluoxetine, which has a long half-life. The dose of the antidepressant should be slowly reduced before stopping.

These newer antidepressants target other neurotransmitters, such as norepinephrine or dopamine, alone or in addition to serotonin. In general, the advantages of the new designer antidepressants are:

They may be better tolerated than the older tricyclic compounds and even some SSRIs, although long-term side effects are not fully known in this group.
Most of these drugs have fewer adverse effects than SSRIs on sexual function.
They may be more effective than SSRIs for severely depressed patients.
Some of these drugs are helpful for additional problems -- such as insomnia, fibromyalgia and similar chronic pain syndromes, or smoking -- that may affect people with depression.

They do share some side effects with other antidepressants, including dizziness and dry mouth.

Dual Inhibitors. Dual inhibitors act directly on two neurotransmitters -- norepinephrine and serotonin. These drugs are also known as serotonin norepinephrine reuptake inhibitors (SNRIs). The following SNRIs are approved for treatment of major depression in adults:

Venlafaxine (Effexor) is similar to Prozac in effectiveness and tolerability for most patients. As with SSRIs, venlafaxine may impair sexual function. The drug can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. It can also cause uterine and vaginal bleeding unrelated to menstruation. Venlafaxine should not be taken during the last trimester of pregnancy as it can cause complications in newborn infants. Some patients report severe withdrawal symptoms, including dizziness and nausea. In 2006, the drug’s manufacturer warned of an increased overdose risk and advised doctors to prescribe their patients only small amounts of venlafaxine pills.
Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. Side effects are generally mild and include dry mouth, nausea, and sleepiness. Patients with narrow-angle glaucoma or patients with liver or kidney diseases should not take duloxetine. Because duloxetine can cause liver damage, patients who drink large quantities of alcoholic beverages should not take it. Signs of liver damage include itching, dark urine, yellowing of skin and eyes (jaundice), and fatigue. Patients should immediately contact their doctor if they experience these symptoms.
Mirtazapine (Remeron) can cause sleepiness, increased appetite, weight gain, and dizziness.

Other Antidepressants with Effects on Multiple Neurotransmitters. Bupropion (Wellbutrin, Zyban) affects the reuptake of serotonin, norepinephrine, and dopamine -- a third important neurotransmitter. In addition to depression, bupropion is also approved for smoking cessation and for treating seasonal affective disorder (SAD). Bupropion causes less sexual dysfunction than SSRIs. About 25% of patients experience initial weight loss. Side effects include restlessness, agitation, sleeplessness, headache, and stomach problems. Bupropion has a risk for seizures, which increases with higher doses. High doses may also cause dangerous heart arrhythmias.

Before the introduction of SSRIs, tricyclics were the standard treatment for depression.

Tricyclics are sometimes grouped into two categories:

Tertiary amines include amitriptyline (Elavil, Endep) and imipramine (Tofranil).
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects, including drowsiness, than tertiary amines, but they are as toxic in high amounts.

Less commonly used tricyclics include doxepin (Sinequan), amoxapine (Asendin), maprotiline (Ludiomill), protriptyline (Vivactil), trimipramine (Surmontil), mianserin (Bolvidon), and dothiepin (Prothiaden).

Tricyclics are as effective for treating depression but they have many side effects. They may offer benefits for many people with dysthymia, who generally do not respond to SSRIs. They may also be prescribed in lower dosages to be taken at night to help with insomnia.

Side Effects of Tricyclics. Side effects are common with these medications. In fact, in an analysis of studies, more tricyclic users discontinued their drugs due to side effects than did SSRI or MAOI users. Those most often reported include:

Dry mouth
Constipation
Blurred vision
Sexual dysfunction
Weight gain
Difficulty urinating
Drowsiness
Dizziness -- blood pressure may drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects:

They tend to cause disturbances in heart rhythm, which can pose a danger for some patients with certain heart diseases. Care should be taken when these medications are prescribed to the elderly and to those at risk of overdose.
Also of concern are reports that tricyclics, particularly imipramine as well as mianserin and dothiepin, may increase the risk for a lung disease called idiopathic pulmonary fibrosis (IPF), which can cause lung inflammation and scarring. Initial symptoms are breathlessness and dry cough.
Tricyclics can be fatal with an overdose.
Protriptyline can cause sun sensitivity. People who take this drug should take precautions against sunlight when they go outdoors.

Monoamine oxidase inhibitors (MAOIs) block monoamine oxidase, an enzyme which has negative effects on many of the neurotransmitters that are important for well-being. MAOIs include phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate). Because these drugs can have very severe side effects, they are usually prescribed only when other types of antidepressants do not help. Research indicates that MAOIs are an effective option for atypical and treatment-resistant depression.

Newer MAOIs, such as selegiline (Eldepryl, Movergan), target only one form of the MAOI enzyme. They may cause fewer side effects than older MAOIs. In 2006, a skin patch form of selegiline (Emsam) was approved for treatment of major depressive disorder in adults.

Candidates for MAOIs. MAOIs may be effective for the following conditions:

Atypical depression
Eating disorders
Post-traumatic stress disorder
Borderline personality

Side Effects. MAOIs commonly cause the following side effects:

Orthostatic hypotension (a sudden drop in blood pressure upon standing)
Drowsiness or insomnia
Dizziness
Sexual dysfunction
The most serious side effect is severe hypertension (high blood pressure), which can be brought on by eating certain foods having high tyramine content. Such foods include aged cheeses, most red wines, sauerkraut, vermouth, chicken livers, dried meats and fish, canned figs, fava beans, and concentrated yeast products.
MAOIs can cause birth defects and should not be taken by pregnant women.

Very dangerous side effects, such as serotonin syndrome, can occur from interactions with other antidepressants, including SSRIs. Serotonin syndrome is a potentially fatal condition that is caused by the interaction of serotonergic drugs. Symptoms include confusion, agitation, sweating and shivering, and muscle spasms. There should be at least a 2-week break between taking MAOIs and other antidepressants. MAOIs can have serious interactions with other drugs as well, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctors any other medications they are taking.

If patients fail to respond to antidepressants, doctors may try adding on a different type of drug. (This combination strategy is called “augmentation” or “adjunctive treatment”.) Atypical antipsychotics are drugs that are usually prescribed for schizophrenia or bipolar disorder, but they can also play a role in the treatment of severe depression. In 2007, aripiprazole (Abilify) was approved in combination with antidepressant therapy for treatment of adults with major depressive disorder. Investigators are also studying whether combination treatment with the atypical antipsychotic risperidone (Risperdal) can help patients with major depression achieve remission.

Ketamine. Ketamine, an anesthetic drug, may be helpful for patients with severe treatment-resistant depression. In a small preliminary study, a single intravenous dose of ketamine helped patients quickly recover from depression within 2 hours, and some patients sustained benefits for up to a week. (Standard antidepressant drugs usually take about 8 weeks to have an effect.) Ketamine blocks the NMDA brain protein receptor, which is involved in glutamate regulation. Glutamate is a brain chemical that is thought to be involved in depression.

Psychotherapy

Among the various psychotherapies, cognitive-behavioral therapy appears to be the most effective approach. If psychotherapy is used alone without medications, benefits should be evident within 8 weeks and symptoms should be fully resolved by 12 weeks. If these conditions are not met, then the patient should strongly consider antidepressant drugs.

In a major analysis of four randomized comparative studies, cognitive behavior therapy worked as well as antidepressants in treating severe depression for many patients. Much of the success of psychologic therapy depends on the skill of the therapist. Many studies suggest that combining cognitive therapy with antidepressants offer the greatest benefits for many patients, particularly for dysthymia (chronic depression).

Medical evidence also has found that the benefits of cognitive therapy persist after treatment has ended. Cognitive behavioral therapy has been shown to help prevent future suicide attempts in patients with a history of suicidal behavior.

Best Candidates. Cognitive therapy may be particularly helpful for the following patients:

Patients with atypical depression
Adolescents with mild symptoms of major depression
Women with non-psychotic postpartum depression
Children of parents with the disorder -- in this case, therapy should involve the whole family.
Cognitive therapy does not appear to be as beneficial as antidepressants for most patients with dysthymia.

Approach. This approach focuses on identification of distorted perceptions that patients may have of the world and themselves, on changing these perceptions, and on discovering new patterns of actions and behavior. These perceptions, known as schemas, are negative assumptions developed in childhood that can precipitate and prolong depression. Cognitive therapy works on the principle that these schemas can be recognized and altered, thereby changing the response and eliminating the depression.

First, the patient must learn to recognize depressive reactions and thoughts as they occur, usually by keeping a journal of feelings about, and reactions to, daily events.
The patient is often given "homework" that tests old negative assumptions against reality and demands different responses.
Then, the patient and therapist examine and challenge these entrenched and automatic reactions and thoughts.
As the patient begins to understand the underlying falseness of the assumptions that cause depression, they can begin substituting new ways of coping.

Over time, such exercises help build confidence and eventually alter behavior. Patients may take group or individual cognitive therapy. Cognitive therapy is a time-limited treatment, typically lasting 12 - 14 weeks. Extending this period, however, may help prevent relapse. In one study, therapy was continued for 10 sessions over an additional 8 months. This extended treatment significantly reduced the risk of recurrence. In fact, some experts believe that short-term therapy is not effective for patients with chronic or relapsing psychiatric disorders.

Based in part on psychodynamic theory, interpersonal therapy acknowledges the childhood roots of depression, but focuses on symptoms and current issues that may be causing problems. IPT is not as specific as cognitive or behavioral therapy, and all work is done during the sessions. The therapist seeks to redirect the patient's attention, which has been distorted by depression, toward the daily details of social and family interaction. The goals of this treatment method are improved communication skills and increased self-esteem within a short period (3 - 4 months of weekly appointments) of time. Among the forms of depression best served by IPT are those caused by distorted or delayed mourning, unexpressed conflicts with people in close relationships, major life changes, and isolation.

The intent of supportive psychotherapy or attention intervention is to provide the patient with a nonjudgmental environment by offering advice, attention, and sympathy. Supportive therapy appears to be particularly helpful for improving compliance with medications by giving reassurance, especially when setbacks and frustration occur.

Other Treatments

Electroconvulsive therapy (ECT) is commonly called shock treatment. It has received bad press, in part for its potential memory-depleting effect. Since its introduction in the 1930s, ECT has been significantly refined, and is now considered an effective and safe treatment for severe depression in the appropriate situation. It is especially effective for patients with severe depression who experience delusions and hallucinations. Maintenance ECT may also help prevent relapse.

Candidates for ECT. ECT may be helpful for the following patients with severe depression:

Patients who cannot, for any reason, take antidepressant drugs
Suicidal patients
Elderly patients who are psychotic and depressed
Pregnant women with severe depression
Patients with certain heart problems
Young patients who fit the adult criteria for ECT

The Procedure. In general, hospitalization is not necessary. ECT involves the following steps:

The patient receives a muscle relaxant and short-acting anesthetic.
A small amount of electric current is sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
Most patients receive 6 treatments, spaced every 2 - 5 days. Others receive up to 15 treatments, followed by 6 - 12 additional treatments spaced every other week or longer for another 2 - 4 months.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Concerns about permanent memory loss appear to be unfounded.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses that target affected areas of the brain. This investigational treatment is similar to electroconvulsive therapy (ECT) but, unlike ECT, it is more precise. However, it is not yet clear whether it as effective as ECT. Researchers are continuing to refine rTMS techniques to improve treatment outcomes.

Vagus nerve stimulation (VNS) is a procedure that is effective for certain patients with epilepsy, and is now showing some success in patients with treatment-resistant depression

VNS involves implanting a battery-powered device under the skin in the upper left of the chest. The neurologist programs the device to deliver mild electrical stimulation to the vagus nerve. The two vagus nerves are the longest nerves in the body. They run along each side of the neck, then down the esophagus to the gastrointestinal tract. The vagus nerve travels to areas of the brain that control functions such as sleep and mood.

Studies report response rates of 35 - 46% in appropriate candidates with treatment-resistant depression. VNS is approved by the FDA for long-term treatment of chronic depression in adults who have not responded to typical treatments for their major depressive episode. Patients who use VNS may continue to show improvement in both their depression symptoms and quality of life.

Vagal stimulation can cause shortness of breath, hoarseness, sore throat, coughing, ear and throat pain, or nausea and vomiting. These side effects can be reduced or eliminated by reducing the intensity of stimulation. Long-term studies on patients with epilepsy have reported no serious adverse side effects, although the treatment may cause lung function deterioration in some people with existing lung disease.

The vagus nerves branch off the brain on either side of the head and travel down the neck, along the esophagus to the intestinal tract. They are the longest nerves in the body, and affect swallowing and speech. The vagus nerves also connect to parts of the brain involved in seizures. In many seizures disorders, electrical stimulation of the vagus nerves may help relieve symptoms.

Phototherapy is recommended as treatment for seasonal affective disorder (SAD), particularly for patients who do not wish to try antidepressants.

The Procedure. The procedure is noninvasive and simple. It is best performed immediately after waking in the morning. The patient sits a few feet away from a box-like device that emits very bright fluorescent light (10,000 lux) for about 30 minutes every day.

Some people report mood improvement as early as 2 days after treatment. In others, depression may not lift for 3 - 4 weeks. If no improvement is experienced after that, depressive symptoms will be unlikely to respond to phototherapy. Phototherapy may work best when combined with cognitive behavioral therapy.

Side Effects. Side effects include headache, eye strain, and irritability, although these symptoms tend to disappear within a week. Patients taking light-sensitive drugs (such as those used for psoriasis), certain antibiotics, or antipsychotic drugs should not use light therapy. Patients should be examined by an ophthalmologist before undergoing this treatment.

A surgical technique called cingulotomy interrupts the cingulate gyrus, a bundle of nerve fibers in the front of the brain, by applying heat or cold. A variation of this procedure using MRI scans to guide the surgeon produced long-term improvement in 53 - 78% of patients with severe intractable depression. The procedure is generally safe with few serious complications. It does not affect intellect or memory.

Some small studies have suggested that acupuncture may help in relieving depression. Larger studies are required to confirm its benefits.

Lifestyle Changes

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

St. John's wort (Hypericum perforatum) is an herbal remedy that may help some patients with mild-to-moderate depression. It does not appear to help patients with moderate or severe depression.

The herb St. John's wort is believed to be helpful in relieving mild-to-moderate depression, but should only be taken under a doctor's supervision. Manufacturers of herbal supplements do not need FDA approval to sell the products.

This herbal substance is not regulated, and there is no guarantee of quality in any brands currently available. In fact, in a 2003 study, only 2 of 54 St. John's products bought in Canada and the U.S. contained concentrations of the active ingredients that fell within 10% of the claims on the labels.

The following guidelines are recommended:

People with depression should not use St. John's wort without consulting a doctor. Children and pregnant or nursing women should not take this substance.
People should purchase brands only from well-established manufacturers.
Although no specific dose levels have been established, evidence suggests taking 900 mg daily (300 mg taken 3 times a day or 450 mg taken twice a day).
It takes between 2 - 3 weeks for the herb to have an effect.
St. John's wort should not be combined with other antidepressants. This herb may also interact with other types of medications and increase or decrease their potency. St. John's wort can increase the risk for bleeding when used with blood-thinning drugs. It can also reduce the strength of certain drugs including cancer and HIV treatments.

Side Effects. Side effects are uncommon but may include nausea, dry mouth, allergic reactions, and fatigue. This herb may increase sensitivity to light (photosensitivity). Some people have reported temporary nerve damage after sun exposure, specifically pain and tingling on sun-exposed areas.

Carbohydrates and Tryptophan. Some people report relief from depression by eating foods or diet supplements that boost levels of tryptophan, an amino acid involved in the production of serotonin. There are high-carbohydrate drinks available over the counter that increase tryptophan levels and may alleviate depression associated with premenstrual syndrome for about 3 hours. Simply eating a high amount of carbohydrates, however, is not a solution for depression.

Impurities found in diet supplements containing L-tryptophan itself have caused cases of eosinophilia-myalgia syndrome, a condition that elevates certain white blood cells and can be fatal. Supplements containing L-tryptophan are currently banned in the U.S. by the FDA.

Fish Oil. Some evidence suggests that an imbalance in the ratio of specific fatty acids (omega-6 to omega-3) may increase the risk for depression. Both are polyunsaturated fats, but omega-6 fatty acids are mostly found in corn, safflower, soybean, and sunflower oil whereas omega-3 fatty acids are found in fish oil, canola oil, soybeans, flaxseed, and certain nuts and seeds.

The bottom line may be to increase intake of omega-3 rich foods, such as fish, nuts, and canola oil, and reduce consumption of foods containing omega-6 fatty acids, such as corn and sunflower oils. Such a dietary approach is healthy in any case. Researchers are studying whether eating fish or taking fish oil supplements can reduce depression. Small preliminary studies suggest that these dietary approaches may be helpful for some patients. Scientists are also investigating which type of fish oil compound -- eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) -- provides the greatest benefit.

Omega-3 fatty acids, found in oily fish and flaxseed and canola oils, may be beneficial to people with depression.

Vitamins and Other Supplements. Certain B vitamins have been associated with some protection against depression.

Vitamin B-3 (niacin) is important in the production of tryptophan and is produced from processing vitamin B3 (niacin). Dietary sources of niacin include oily fish (such as salmon or mackerel), pork, chicken, dried peas and beans, whole grains, seeds, and dried fortified cereals.
Vitamin B-12 and calcium supplements may help reduce depression that occurs before menstruation. One study also suggested that calcium might help prevent postpartum depression.
Low levels of folate, a B vitamin, may be associated with depression. Researchers are studying whether folate supplements may help enhance the effectiveness of SSRIs and other antidepressants.

Increasingly studies are reporting major benefits from exercise for people with depression.

Aerobics. Either brief periods of intense training or prolonged aerobic workouts can raise chemicals in the brain, such as endorphins, adrenaline, serotonin, and dopamine that produce the so-called runner's high. And, of course, weight loss and increased muscle tone can boost self-esteem.

Yoga. Yoga practice, which involves rhythmic stretching movements and breathing, may help improve and stabilize mood.

Click the icon to see an image depicting the practice of yoga.

A strong network of social support is important for both prevention and recovery from depression. Support from family and friends must be healthy and positive. One study of depressed women showed, however, that overprotective as well as very distant parenting was associated with a slow recovery from depression. Studies indicate that people with strong spiritual faiths have a lower risk for depression. Such faith does not require an organized religion. People with depression might find solace from less structured sources, such as those that teach meditation or other methods for obtaining spiritual self-fulfillment.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.dbsalliance.org -- Depression and Bipolar Support Association
www.fda.gov/cder/drug/antidepressants -- FDA Antidepressant Use in Children, Adolescents, and Adults
www.parentsmedguide.org -- American Psychiatric Association-sponsored information on pediatric antidepressants
www.nami.org -- National Alliance on Mental Illness
www.nmha.org -- Mental Health America
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.psych.org -- American Psychiatric Association
www.apa.org -- American Psychological Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.postpartum.net -- Postpartum Support International
www.mentalhealth.samhsa.gov -- National Mental Health Information Center
www.mentalhealth.samhsa.gov/suicideprevention/concerned.asp -- National Strategy for Suicide Prevention (if contemplating suicide, call 1-800-273-TALK)
www.suicidology.org -- American Association of Suicidology

References

Allen JJ, Schnyer RN, Chambers AS, Hitt SK, Moreno FA, Manber R. Acupuncture for depression: a randomized controlled trial. J Clin Psychiatry. 2006 Nov;67(11):1665-73.

Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM; National Birth Defects Prevention Study. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2684-92.

Bridge JA, Iyengar S, Salary CB, et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007 Apr 18;297(15):1683-96.

Cheung AH, Zuckerbrot RA, Jensen PS, Ghalib K, Laraque D, Stein RE; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): II. Treatment and ongoing management. Pediatrics. 2007 Nov;120(5):e1313-26.

Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures. Arch Intern Med. 2007 Jun 25;167(12):1240-5.

Eranti S, Mogg A, Pluck G, et al. A randomized, controlled trial with 6-month follow-up of repetitive transcranial magnetic stimulation and electroconvulsive therapy for severe depression. Am J Psychiatry. 2007 Jan;164(1):73-81.

Frederikse M, Petrides G, Kellner C. Continuation and maintenance electroconvulsive therapy for the treatment of depressive illness: a response to the National Institute for Clinical Excellence report. J ECT. 2006 Mar;22(1):13-7.

George MS, Nahas Z, Borckardt JJ, et al. Brain stimulation for the treatment of psychiatric disorders. Curr Opin Psychiatry. 2007 May;20(3):250-4; discussion 247-9.

Gross M, Nakamura L, Pascual-Leone A, Fregni F. Has repetitive transcranial magnetic stimulation (rTMS) treatment for depression improved? A systematic review and meta-analysis comparing the recent vs. the earlier rTMS studies. Acta Psychiatr Scand. 2007 Sep;116(3):165-73.

Hetrick S, Merry S, McKenzie J, Sindahl P, Proctor M. Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004851.

Institute for Clinical Systems Improvement. Health Care Guideline: Major Depression in Adults in Primary Care. Tenth addition. May 2007.

Jarema M. Atypical antipsychotics in the treatment of mood disorders. Curr Opin Psychiatry. 2007 Jan;20(1):23-9.

Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial. BMC Med. 2006 Jun 23;4:14.

Kellner CH, Knapp RG, Petrides G, et al. Continuation electroconvulsive therapy vs pharmacotherapy for relapse prevention in major depression: a multisite study from the Consortium for Research in Electroconvulsive Therapy (CORE). Arch Gen Psychiatry. 2006 Dec;63(12):1337-44.

Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry. 2007;68 Suppl 8:35-41.

Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61.

Louik C, Lin AE, Werler MM, Hernández-Díaz S, Mitchell AA. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med. 2007 Jun 28;356(26):2675-83.

Mahmoud RA, Pandina GJ, Turkoz I, et al. Risperidone for treatment-refractory major depressive disorder: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):593-602.

Papakostas GI, Shelton RC, Smith J, Fava M. Augmentation of antidepressants with atypical antipsychotic medications for treatment-resistant major depressive disorder: a meta-analysis. J Clin Psychiatry. 2007 Jun;68(6):826-31.

Rapaport MH. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: the state of the art. J Clin Psychiatry. 2007;68 Suppl 8:42-6.

Rohan KJ, Roecklein KA, Tierney Lindsey K, et al. A randomized controlled trial of cognitive-behavioral therapy, light therapy, and their combination for seasonal affective disorder. J Consult Clin Psychol. 2007 Jun;75(3):489-500.

Ruhé HG, Huyser J, Swinkels JA, Schene AH. Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry. 2006 Dec;67(12):1836-55.

Stewart JW. Treating depression with atypical features. J Clin Psychiatry. 2007;68 Suppl 3:25-9.

Thachil AF, Mohan R, Bhugra D. The evidence base of complementary and alternative therapies in depression. J Affect Disord. 2007 Jan;97(1-3):23-35. Epub 2006 Aug 22.

Zuckerbrot RA, Cheung AH, Jensen PS, Stein RE, Laraque D; GLAD-PC Steering Group. Guidelines for Adolescent Depression in Primary Care (GLAD-PC): I. Identification, assessment, and initial management. Pediatrics. 2007 Nov;120(5):e1299-312.

Review Date:
12/25/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

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adam.com

Depression

FitSugar — Wed, 08 Oct 2008 17:34:54 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Depression is a mood disorder in which feelings of loss, anger, sadness, or frustration interfere with everyday life. Depression affects about 17 million Americans each year. It can be mild, moderate, or severe and occur as a single episode, recurring episodes, or chronic depression (lasting more than 2 years).

The primary types of depression include:

Major depression -- five or more symptoms must be present. An episode must last at least 2 weeks, but tends to continue for 20 weeks. (A mood disorder is classified as minor depression if less than five depressive symptoms are present for at least 2 weeks.)
Dysthymia-- a chronic, generally milder form of depression. Symptoms are similar to major depression but more mild in degree.
Atypical depression-- depression accompanied by unusual symptoms, such as hallucinations, delusions, and physical rigidity

Other common forms of depression include:

Postpartum depression-- experienced by 8 - 20% of women following delivery
Premenstrual dysphoric disorder (PDD)-- experienced by 3 - 8% of women. Depressive symptoms occur 1 week prior to menstruation and disappear following menstruation.
Seasonal affective disorder (SAD)-- experienced by 5% of adults, the majority of whom are women. It occurs during the fall-winter season and disappears during the spring-summer season.

Depression may also occur with mania (known as manic-depression or bipolar disorder). In this condition, moods cycle between mania and depression.

Signs and Symptoms

While it is normal for most people to feel "down in the dumps" on occasion, someone with major depression feels significantly depressed for a prolonged period of time, has difficulty enjoying acts that were once pleasurable, and experiences at least five of the following symptoms for 2 weeks or more:

Sleep disturbances -- at least 90% of people with depression have either insomnia (sleeplessness) or hypersomnia (excessive sleeping).
Significant change in appetite (often resulting in either weight loss or weight gain)
Fatigue and loss of energy
Feelings of worthlessness, self-hate, and inappropriate guilt
Extreme difficulty concentrating
Either agitation, restlessness, and irritability or inactivity and withdrawal
Recurring thoughts of death or suicide
Feelings of hopelessness

Although not generally considered to be defining characteristics of depression, many people with the condition report a lack of sex drive and sudden bursts of anger.

Causes

The causes of depression are complex and involve a combination of biologic, genetic, and environmental factors. People with depression may have abnormal levels of certain brain chemicals, including serotonin, acetylcholine, and catecholamines (such as dopamine). The following may alter the levels of these brain chemicals and contribute to development of depression:

Heredity -- a recently identified gene called SERT that regulates the brain chemical serotonin has been linked to depression.
Chronic stress (such as from loss, abuse, or deprivation in early childhood)
Amount of exposure to light
Sleep disturbances
Social isolation
Nutritional deficiencies
Serious medical conditions, such as heart attack or cancer
Certain medications, including those for high blood pressure, high cholesterol, or irregular heartbeat

Risk Factors

Although depression is a condition that can affect anyone, regardless of age, race, or gender, the following factors may increase your risk for an initial or recurrent episode of depression:

Prior episodes of depression
Family history of depression
Suicide attempt -- a previous attempt of suicide during a major depressive episode increases the likelihood of another episode of depression.
Female gender -- the incidence of depression appears to be greater in women than in men. Some researchers speculate, however, that women may simply report their symptoms more frequently than men, and that men may be more apt to mask their depressive symptoms with alcohol. Therefore, it is still unclear whether women truly have a greater risk for depression.
Young adulthood or middle age -- the highest occurrence of depression is between the ages of 25 - 44. The elderly are also at particular risk due to death of loved ones, physical illness, and loss of independence.
Stressful life events (such as the death of a loved one), particularly if the event occurs at a young age
Postpartum period
Chronic medical or psychological conditions, including autoimmune diseases (such as lupus), cancer, heart disease, chronic headaches, chronic pain, anxiety, obsessive-compulsive disorder, and borderline personality disorder. Medical conditions that cause shifts in hormones, such as thyroid disorders or menopause, may also contribute to depression.
History of abuse (such as mental, physical, or sexual)
Lack of social support system (such as a network of close friends or family)
Current or past alcohol or drug abuse -- 25% of people with addictions have depression.

Diagnosis

If feelings of depression or any of the related symptoms are present, it is important to address them with a doctor or someone who can help direct care appropriately. Unfortunately, many people with depression tend to refrain from disclosing any or all of their symptoms in this setting. Occasionally, even when the symptoms are discussed during an appointment, a doctor may try to treat them individually, rather than recognizing the complete picture of depression. Working together with a primary care doctor is extremely important because they are often the health care providers who make a referral to a psychiatrist who, in turn, makes a definite diagnosis of depression. Proper diagnosis of depression is the first step toward proper treatment.

Only psychiatrists can prescribe medication, but psychologists and social workers, as well as psychiatrists, use psychotherapy as an important mode of treatment. These specialists will often administer a screening test, such as the Beck Depression Inventory or the Hamilton Rating Scale, which consists of about 20 questions that assess an individual's risk for depression. Even before these psychological screening tests, however, several blood tests will be performed to determine whether nutrient deficiencies or underlying medical conditions (such as a thyroid disorder) may be causing or contributing to depression.

Although the vast majority of people with depression are treated as outpatients, hospitalization is necessary for people who intend to, or do, attempt suicide, and may be necessary under other circumstances as well.

Preventive Care

The following steps can help prevent depression or decrease the chances of relapse:

Adequate sleep, regular exercise, and a balanced, healthy diet may help prevent depression and diminish symptoms of this mood disorder.
Mind-body techniques, such as biofeedback, meditation, and tai chi, are effective ways to prevent or reduce symptoms associated with depression.
Psychotherapy directed at coping skills generally helps prevent relapse.
Family therapy may prevent children or teens of depressed parents from becoming depressed later in life.
Compliance with the prescribed treatment regimen decreases the chance of relapse.

Treatment Approach

People with depression have several options for treatment, but a combination of psychotherapy and antidepressant medications is the regimen of choice, particularly for people with major depression. Cognitive-behavioral therapy appears to be the most effective type of psychotherapy, particularly for adolescents and people with atypical or postpartum depression. As many as 90% of people with depression improve from a combination of psychotherapy and antidepressants. However, adverse side effects from certain medications make it difficult for many to take their medications. Some complementary and alternative therapies may be helpful in reducing the side effects from such medications, while other complementary and alternative therapies may actually diminish the symptoms of depression.

Lifestyle

Exercise

Studies have consistently shown that regular exercise (either aerobic or strength and flexibility training) significantly reduces depressive symptoms in people with mild to moderate depression and improves the mood of people with major depression. Some even suggest that exercise may be as effective as psychotherapy for people with mild-to-moderate depression, although additional research is needed. In the meantime, exercise can be used safely in conjunction with medication for those with depression.

Medications

Antidepressant medications are very effective; reports indicate that they are 90% successful in treating depression. In general, medications are taken for at least 4 - 6 months to assure complete and effective treatment. However, antidepressants often cause adverse side effects, making it difficult for some people to comply with taking their medications. Medications must not be stopped before first talking with a physician. Most antidepressants cause withdrawal symptoms if they are not discontinued slowly over time with guidance from a physician.

There are several classes of antidepressant medications, including:

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs increase the activity of a chemical in the brain called serotonin. Most health care providers will prescribe SSRIs before any other antidepressant medication for depression, in part because the side effects associated with SSRIs are generally fewer than for other classes of antidepressants. Typical side effects caused by SSRIs include stomach upset, weight gain or loss, drowsiness, sexual dysfunction (such as impotence, decreased libido, and diminished orgasm), headache, jaw grinding, and apathy. Very unusual side effects from this class of prescription drugs include extreme agitation, impulsivity, tremors, and insomnia. People who discontinue taking SSRIs due to side effects usually attribute their discontent to sexual dysfunction.

Drugs classified as SSRIs include:

Fluoxetine
Sertraline
Paroxetine -- most likely in this class to cause sexual dysfunction
Fluvoxamine
Citalopram -- least likely in this class to cause sexual dysfunction

Another group of antidepressant medications (which are similar to SSRIs, but target other brain chemicals in addition to serotonin) may cause fewer negative sexual side effects. These include:

Bupropion -- should not be used if there is history of or risk for seizure
Nefazodone -- no sexual dysfunction reported. It begins to work very quickly and may cause a decrease in blood pressure when going from lying or sitting to standing.
Venlafaxine -- may impair sexual function and is not recommended in the elderly. It may improve quality of life more effectively than other antidepressants, but can cause irregular heart rhythm. Withdrawal from the medication is difficult.
Mirtazapine -- may be particularly effective if feelings of anxiety are also present. It helps with insomnia but may cause drowsiness, blurred vision, weight gain, and damage to production of cells in the bone marrow (very rare).
Maprotiline -- may cause dry mouth, drowsiness, sensitivity to the sun, and seizures

Tricyclic Antidepressants

Tricyclics increase the activity of the brain chemicals serotonin and norepinephrine. They are as effective as SSRIs, but are usually prescribed only to those who do not respond well to SSRIs because side effects are quite common and are usually less tolerable. Tricyclic antidepressants include:

Amitriptyline
Amoxapine -- increases risk of seizure in those who are prone to have a seizure
Clomipramine -- used for obsessive-compulsive disorder
Desipramine
Doxepin -- may help with insomnia
Imipramine -- may cause a rare lung disorder called idiopathic pulmonary fibrosis
Nortriptyline -- less risk of irregular heart rhythm than others in this class
Protriptyline -- less drowsiness than others in this class and may even cause weight loss and sun sensitivity
Trimipramine -- high risk for irregular heart rhythm

Side effects of tricyclics may include:

Dry mouth
Blurred vision
Constipation
Sexual dysfunction
Weight gain
Dizziness
Drowsiness
Urinary urgency (a sense that one has to urinate even when the bladder is empty)
Drop in blood pressure when going from lying or sitting to standing (causes dizziness and lightheadedness)
Irregular heart rhythm

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs boost levels of norepinephrine, dopamine, and serotonin in the brain. MAOIs are generally prescribed only when other antidepressants have not been effective, which may occur in people with atypical depression. People who take MAOIs may experience a sharp increase in blood pressure after consuming food or drink containing the amino acid tyramine (found in such foods as aged cheeses and red wine). MAOIs also negatively interact with other medications, including Ritalin (used for attention deficit hyperactivity disorder) and pseudoephedrine (decongestant in many over-the-counter and prescription medications), and should not be taken with other classes of antidepressants.

MAOIs include:

Phenelzine -- should be avoided by people with a history of seizures or bipolar disorder (manic-depression)
Isocarboxazid -- side effects include drowsiness, sexual dysfunction, weakness, trembling, and blurred vision.
Tranylcypromine -- should not be used if there is any history of kidney disease or bipolar disorder

Surgery and Other Procedures

Electroconvulsive Therapy (ECT) for depression is usually reserved for when all other therapies have been unsuccessful. In this procedure, a small electrical current induces a seizure lasting approximately 40 seconds. A muscle relaxant and mild sedative are administered prior to the procedure. ECT is generally repeated every 2 - 5 days for a total of six treatments. It may cause temporary confusion, memory impairment, headache, muscle aches, irregular heart rhythm, or nausea.
Magnetic Resonance Imaging (MRI)-Guided Cingulotomy involves the application of an electrical current to a specific part of the brain. The MRI is used as a guide for an exact placement. Long-term improvement has been reported using this technique in over 50% of people with depression who have not responded to other treatment methods.

Nutrition and Dietary Supplements

A comprehensive treatment plan for depression may include a range of complementary and alternative therapies. Preliminary studies suggest that nutritional supplements may reduce the symptoms of some depression. Ask your team of health care providers about the best ways to incorporate these therapies into your overall treatment plan. Always tell your health care provider about the herbs and supplements you are using or considering using.

Following these nutritional tips may help reduce symptoms:

Try to eliminate potential food allergens, including dairy, wheat (gluten), corn, preservatives, and food additives. Your health care provider may want to test for food sensitivities.
Eat antioxidant foods, including fruits (such as blueberries, cherries, and tomatoes), and vegetables (such as squash and bell peppers).
Eat foods high in B-vitamins and calcium, such as almonds, beans, whole grains (if no allergy), dark leafy greens (such as spinach and kale), and sea vegetables such as kelp and dulce.
Avoid refined foods, such as white breads, pastas, and especially sugar.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
Use healthy oils for cooking, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise at least 30 minutes daily, 5 days a week.

You my address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, one to two capsules or one tablespoonful oil one to three times daily, to help decrease inflammation and help with mental balance.
Vitamin C, 500 - 1000 mg one to three times daily, as an antioxidant and for immune support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.
5-hydroxytryptophan (5-HTP), 50 mg two to three times daily, for mood stabilization. Ask your health care provider about potential prescription interactions.
Probiotic supplement (containing Lactobacillus acidophilus and other species), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
SAMe (s-adenosyl-L-methionine), 100 - 200 mg before breakfast daily, for mood improvement.
Dihydroepiandosterone (DHEA), start at 5 mg three times a day and work up to 100 mg per day for 7 - 12 months. It is recommended to use DHEA under the supervision of a qualified health care provider. If adverse effects develop, discontinue use.
L-theanine, 200 mg one to three times daily, for nervous system support.
Melatonin, 2 - 5 mg one hour before bedtime, for sleep and immune protection. Ask your health care provider about potential prescription interactions.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day. You may use tinctures alone or in combination as noted.

St. John's wort (Hypericum perforatum) standardized extract, 300 mg two to three times per day, for depression. Check with your health care provider if you are taking prescription medications.
Kava kava (Piper methysticum) standardized extract, 100 - 250 mg one to three times daily, as needed for symptoms of stress and anxiety. Talk with your health care provider before taking kava kava if you have an unhealthy liver.
Ginkgo (Ginkgo biloba) standardized extract, 40 - 80 mg three times daily, for blood flow and depression.
Green tea ( Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant and general health effects. Use caffeine-free products. You may also prepare teas from the leaf of this herb.
Rhodiola ( Rhodiola rosea ) standardized extract, 100 - 600 mg daily, for antioxidant and anti-stress activity.

Acupuncture

Two randomized, controlled, clinical trials suggest that electroacupuncture may reduce symptoms of depression as effectively as amitriptyline, a tricyclic antidepressant medication. Electroacupuncture involves the application of a small electrical current through acupuncture needles. Other studies suggest that acupuncture may be effective for people with mild depression and for those with depression related to a chronic medical illness. Further research is warranted in this area.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies to alleviate the symptoms of depression based on their knowledge and experience.

Before prescribing a remedy, homeopaths take into account a person’s constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual. A few homeopathic remedies that may work for depression include:

Ignatia -- for a sudden sense of grief or disappointment following the death of a loved one, the end of a romantic relationship, or an unexpected loss of one's job
Natrum muriaticum -- for grief following the death of a loved one or sadness from the end of a romantic relationship

Massage and Physical Therapy

Studies of formerly depressed adolescent mothers, children hospitalized for depression, and women with eating disorders, suggest that massage decreases stress hormone levels, feelings of anxiety, and symptoms of depression. Giving massage may also be beneficial for people who are depressed. Elderly volunteers with depression showed notable improvement in their symptoms when they massaged infants.

Aromatherapy, or the use of essential oils in massage therapy, may also be of value as a supplemental treatment for depression. Theoretically, the smells of the oils elicit positive emotions through the limbic system (the area of the brain responsible for memories and emotions). However, the benefits of aromatherapy appear to be related to the relaxation effects of the treatment as well as to the recipient's belief that the treatment will be beneficial. Essential oils used during massage for depression are quite varied and include:

Lavender ( Lavandula officinalis)
Basil (Ocimum basilicum)
Orange (Citrus aurantium)
Sandalwood (Santalum album)
Lemon (Citrus limonis)
Jasmine (Jasminum spp.)
Sage (Salvia officinalis)
Chamomile (Chamaemelum nobile)
Peppermint (Mentha piperita)
Rosemary (Rosmarinus officinalis)

Mind-Body Medicine

Mind-body therapies and techniques that may be useful as a part of an overall treatment regimen for depression include:

Psychotherapy

Cognitive-behavioral therapy is a type of psychotherapy in which individuals learn to identify and change distorted perceptions about themselves and adapt new behaviors to better cope with the world around them. This therapy is frequently considered the treatment of choice for people with mild-to-moderate depression, but it may not be recommended for those with severe depression. Studies of people with depression indicate that cognitive-behavioral therapy is at least as effective as tricyclic antidepressants. Compared to those treated with antidepressants, people treated with cognitive-behavioral therapy demonstrated similar, or better, results and lower relapse rates.

Other therapeutic approaches that may be applied by a psychiatrist, psychologist, or social worker include:

Psychodynamic psychotherapy -- based on Freud's theories about unresolved conflicts in childhood and depression as a grief process
Interpersonal therapy -- acknowledges childhood roots of depression, but focuses on current problems contributing to depression and is considered very effective treatment for depression
Supportive psychotherapy -- nonjudgmental advice, attention, and sympathy, and this approach may improve compliance with taking medication

Relaxation

One study suggests that relaxation techniques, such as yoga and tai chi, may improve symptoms of depression in people with mild depression.

Meditation

Some researchers believe that mindfulness meditation may prevent depression from recurring in people who once had the condition.

Other Considerations

Pregnancy

Postpartum depression is experienced by 8 - 20% of women following delivery.
The safety of SSRIs and tricyclic antidepressant medications during pregnancy remains uncertain. The physician will provide guidance regarding use or avoidance of antidepressants during pregnancy. The risks and benefits to the mother and the fetus must be weighed in each individual case in order to determine the most appropriate regimen during pregnancy. MAOIs cause birth defects and should be avoided during pregnancy.
Many of the dietary supplements and herbs mentioned here have not been tested for safety during pregnancy. Talk with your doctor or pharmacist.

Warnings and Precautions

People with Parkinson's disease should avoid SSRIs.
People with coronary artery disease should avoid tricyclic antidepressants.
Several herbal remedies and supplements should not be combined with antidepressant medications. Be sure to inform your health care provider of all herbs and supplements you take to avoid adverse interactions.

Prognosis and Complications

Depression is a serious condition that can have a devastating effect on people's lives. It can directly and indirectly contribute to chronic medical conditions, such as heart disease and stroke, because depressed people with these conditions are less likely to engage in healthy behaviors (such as exercise) and more likely to engage in unhealthy behaviors (such as smoking). Suicide is a significant factor in depression. About 15 % of people with a major depressive disorder commit suicide. Depression also significantly shortens the lifespan of the elderly and is associated with the development of memory impairment and dementia.

When left untreated, depression can last up to 2 years. Rates of recurrence are variable: 50% of people who have had one depressive episode will have a second major depressive disorder, 70% will have a third, and 90% will have a fourth. Symptoms of depression usually disappear after menopause in women with premenstrual dysphoric disorder or seasonal affective disorder. Fortunately, there are several treatment options available for people with depression, and the prognosis improves tremendously for those who seek treatment and comply with their regimen.

Supporting Research

Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutrition Rev. 1997;5(5):145-149.

Alpert JE, Mischoulon D, Nierenberg AA, Fava M. Nutrition and depression: focus on folate. Nutrition. 2000;16:544-581.

Anonymous. SAMe for depression. Med Lett Drugs Ther. 1999;41(1065):107-108.

Babyak M, Blumenthal JA, Herman S, et al. Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months. Psychosom Med. 2000;62(5):633-638.

Beniamini Y, Rubenstein JJ, Zaichkowsky LD, Crim MC. Effects of high-intensity strength training on quality-of-life parameters in cardiac rehabilitation patients. Am J Cardiol. 1997;80(7):841-846.

Benjamin J, Agam G, Levine J, Bersudsky Y, Kofman O, Belmaker RH. Inositol treatment in psychiatry. Psychopharmacol Bull. 1995;31(1):167-175.

Benton D, Cook R. The impact of selenium supplementation on mood. Biol Psychiatry. 1991;29(11):1092-1098.

Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998;3(4):271-280.

Bottiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutrition Rev. 1996;54(12):382-390.

Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69(2):228-232.

Bottiglieri T, Hyland K, Reynolds EH. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Drugs. 1994;48(2):137-152.

Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study. Clin Ther. 2000;22(4):411-419.

Briggs CJ, Briggs GL. Herbal products in depression therapy. CPJ/RPC. November 1998;40-44.

Bruinsma KA, Taren DL. Dieting, essential fatty acid intake, and depression. Nutrition Rev. 2000;58(4):98-108.

Cauffield JS, Forbes HJ. Dietary supplements used in the treatment of depression, anxiety, and sleep disorders. Lippincotts Prim Care Pract. 1999;3(3):290-304.

Eich H, Agelink MW, Lehmann E, Lemmer W, Klieser E. Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study. Fortschr Neurol Psychiatr. 2000;68(3):137-144.

Einat H, Karbovski H, Korik J, Tsalah D, Belmaker RH. Inositol reduces depressive-like behaviors in two different animal models of depression. Psychopharmacology. 1999;144:158-162.

Ernst E, Rand JI, Stevinson C. Complementary therapies for depression. Arch Gen Psychiatry. 1998;55:1026-1032.

Field TM. Massage therapy effects. Am Psychol. 1998;53(12):1270-1281.

Field T, Grizzle N, Scafidi F, Schanberg S. Massage and relaxation therapies' effects on depressed adolescent mothers. Adolescence. 1996;31(124):903-911.

Fugh-Berman A, Cott JM. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med. 1999;61:712-728.

Gaster B, Holroyd J. St. John's wort for depression. Arch Intern Med. 2000;160:152-156.

Gelenberg AJ, Wojcik JD, Falk WE, et al. Tyrosine for depression: a double-blind trial. J Affect Disord. 1990;19:125-132.

Hibbeln JR, Salem N. Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy. Am J Clin. 1995;62:1-9.

Horrocks LA, Yeo YK. Health benefits of docosahexaenoic acid (DHA). Pharmacol Res. 1999;40(3):211-225.

Johnson MA. Nutrition and aging--practical advice for healthy eating. J Am Med Womens Assoc. 2004;59(4):262-9.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 247-248.

Kim HL, Streltzer J, GoebertD. St. John's wort for depression: a meta-analysis of well-defined clinical trials. J Nerv Ment Dis. 1999;187:532-539.

Lewy AJ, Bauer VK, Cutler NL, Sack RL. Melatonin treatment of winter depression: a pilot study. Psych Res. 1998;77(1):57-61.

Linde K, Mulrow CD. St. John's wort for depression (Cochrane Review). In: The Cochrane Library, Issue 4, 2000. Oxford: Update Software.

Maes M, DeVos N, Pioli R, et al. Lower serum vitamin E concentrations in major depression another marker of lowered antioxidant defenses in that illness. J Affect Disord. 2000;58:241-246.

Markus R, Panhuysen G, Tuiten A, Koppeschaar H. Effects of food on cortisol and mood in vulnerable subjects under controllable and uncontrollable stress. Physiol Behav. 2000;70(3-4):333-342.

McGinn LK. Cognitive behavioral therapy of depression: theory, treatment, and empirical status. Am J Psychother. 2000;54(2):257-262.

Meyers S. Use of neurotransmitter precursors for treatment of depression. Altern Med Rev. 2000;5(1):64-71.

Morelli V, Zoorob RJ. Alternative therapies: Part 1. Depression, diabetes, obesity. Am Fam Phys. 2000;62(5):1051-1060.

Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, and herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000;294(1):88-95.

Paluska SA, Schwenk TL. Physical activity and mental health. Sports Med. 2000;29(3):167-180.

Pizzorno JE and Murray MT. Textbook of Natural Medicine, Vols 1 & 2. New York, NY: Churchill Livingstone; 1999:1049-1059.

Reus VI. Psychiatric disorders. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:2490-2496.

Roschke J, Wolf CH, Muller MJ, et al. The benefit from whole body acupuncture in major depression. J Affect Disord. 2000;57:73-81.

Rush AJ, George MS, Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment of resistant depressions: a multicenter study. Biol Psychiatry. 2000;47:276-286.

Shaw, K., Turner, J., and Del Mar, C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198.

Tao DJ. Research on the reduction of anxiety and depression with acupunture. Am J Acupunct. 1993;21(4):327-329.

Teasdale JD, Segal Z, Williams MG. How does cognitive therapy prevent depressive relapse and why should attentional control (mindfulness) training help? Behav Res Ther. 1995;33(1):25-39.

Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry. 1999;156:646-649.

Wurtman RJ, Wurtman JJ. Brain serotonin, carbohydrate-craving, obesity and depression. Obes Res. 1995;3(suppl4):477S-480S.

Young SN. The use of diet and dietary components in the study of factors controlling affect in humans: a review. J Psychiatr Neurosci. 1993;18(5):235-244.

Review Date:
11/6/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Stress

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

In This Report

Highlights
Introduction
The Body's Response
Complications
Conditions with Similar Sym...
Treatment
Risk Factors
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Some people are pre-programmed for a heightened response to stress by conditions in the womb. Pregnant women under stress who eat a diet high in protein and low in carbohydrates have babies with higher cortisol levels. Later on, these levels increase in response to stress.
The impact of stress on the heart and circulation system is becoming more clear. Stress causes the body to release inflammatory markers that may worsen heart and circulatory diseases as well as inflammatory disease, such as rheumatoid arthritis. High levels of inflammatory markers are associated with increased risk of heart attack and stroke. Extreme stress can also produce a condition that mimics a heart attack, but is reversible. People under severe stress can experience irregular heart beats that make them susceptible to sudden cardiac death.
Stress also increases the risk of developing type 2 diabetes in women.
Traumatic stress has long been known to cause amnesia, emotional numbness, nightmares, and memory problems. Now it is known that traumatic emotional stress can cause permanent changes in the brain that interfere with the normal way information is accepted, coded, and retrieved.
The good news is that our physical response to stress is increasingly understood. Knowing what occurs at the cellular level may help researchers find more ways to counteract the detrimental physical and emotional effects of stress.

Introduction

Stress affects most people in some way. Acute (sudden, short-term) stress leads to rapid changes throughout the body. Almost all body systems (the heart and blood vessels, the immune system, the lungs, the digestive system, the sensory organs, and brain) gear up to meet the perceived danger.

These stresses could prove beneficial in a critical, life-or-death situation. Over time, however, repeated stressful situations put a strain on the body that may contribute to physical and psychological problems. Chronic (long-term) stress can have real health consequences and should be addressed like any other health concern.

Fortunately, research is showing that lifestyle changes and stress-reduction techniques can help people learn to manage their stress.

People can experience stress from external or internal factors.

External stressors include adverse physical conditions (such as pain or hot or cold temperatures) or stressful psychological environments (such as poor working conditions or abusive relationships). Humans, like animals, can also experience external stressors.
Internal stressors can also be physical (infections, inflammation) or psychological (such as intense worry about a harmful event that may or may not occur). As far as anyone can tell, internal psychological stressors are rare or absent in most animals except humans.

Stressors can also be defined as short-term (acute) or long-term (chronic).

Acute Stress. Acute stress is the reaction to an immediate threat, commonly known as the fight or flight response. The threat can be any situation that is perceived, even subconsciously or falsely, as a danger.

Common acute stressors include:

Noise (which can trigger a stress response even during sleep)
Crowding
Isolation
Hunger
Danger
Infection
High technology effects (playing video games, frequently ringing mobile phones)
Imagining a threat or remembering a dangerous event

Under most circumstances, once the acute threat has passed, levels of stress hormones return to normal. This is called the relaxation response.

Chronic Stress. Frequently, modern life poses ongoing stressful situations that are not short-lived. The urge to act (to fight or flee) must therefore be controlled. Stress, then, becomes chronic.

Common chronic stressors include:

On-going highly pressured work
Long-term relationship problems
Loneliness
Persistent financial worries

The Body's Response

The best way to envision the effect of acute stress is to imagine yourself in a primitive situation, such as being chased by a bear.

In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in organizing systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate an area inside the brain called the amygdala, which appears to trigger an emotional response to a stressful event. In the case of the bear, this emotion is most likely fear.

Release of Neuropeptide S. The brain releases neuropeptide S, a small protein that modulates stress by decreasing sleep and increasing alertness and a sense of anxiety. This gives the person a sense of urgency to run away from the bear.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly, either to fight the bear or to flee from it. It also interferes with the ability to handle difficult social or intellectual tasks and behaviors during that time.

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (such as the large bear) would be critical for avoiding such threats in the future.

The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid, and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The effect on the immune system from confrontation with the bear is similar to organizing a defensive line of soldiers to potentially critical areas. The steroid hormones reduce the activity in parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be repositioned. These immune-boosting troops are sent to the body's front lines where injury or infection is most likely to occur, such as the skin and the lymph nodes.

As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The stress effect moves blood flow away from the skin to support the heart and muscle tissues. This also reduces blood loss in the event that the bear causes a wound. The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Stress shuts down digestive activity, a nonessential body function during short-term periods of hard physical work or crisis.

Once the threat has passed and the effect has not been harmful (for example, the bear has not wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also return to normal.

Complications

In prehistoric times, the physical changes in response to stress were an essential adaptation for meeting natural threats. Even in the modern world, the stress response can be an asset for raising levels of performance during critical events, such as a sports activity, an important meeting, or in situations of actual danger or crisis.

If stress becomes persistent and low-level, however, all parts of the body's stress apparatus (the brain, heart, lungs, vessels, and muscles) become chronically over- or under-activated. Such chronic stress may produce physical or psychological damage over time. Acute stress can also be harmful in certain situations, particularly in individuals with preexisting heart conditions.

Studies suggest that the inability to adapt to stress is associated with the onset of depression or anxiety. In one study, two-thirds of subjects who experienced a stressful situation had nearly 6 times the risk of developing depression within that month.

Some evidence suggests that repeated release of stress hormones produces hyperactivity in the hypothalamic-pituitary-adrenal (HPA) system, and disrupts normal levels of serotonin, the nerve chemical that is critical for feelings of well-being. Some people appear to be more at risk for an overactive HPA system under stress, including those with the personality traits that cause perfectionism. Certainly, on a more obvious level, stress reduces the quality of life by reducing feelings of pleasure and accomplishment. In addition, relationships are often threatened in times of stress.

The full impact of mental stress on heart disease is just coming to light, but the underlying mechanisms are not always clear. Stress can certainly influence the activity of the heart when it activates the automatic part of the nervous system that affects many organs, including the heart. Such actions and others could theoretically affect the heart badly in several ways:

Sudden stress increases the pumping action and rate of the heart, while at the same time causing the arteries to constrict (narrow). This restricts blood flow to the heart. A 2002 study suggested that such actions may be responsible for some cases of acute stress that have been associated with a higher risk for serious heart problems. These problems include heart rhythm abnormalities and heart attacks, and even death in people with heart disease.
Emotional effects of stress alter the heart rhythms, which could pose a risk for serious arrhythmias (rhythm abnormalities) in people with existing heart rhythm disturbances.
Stress causes blood to become stickier (possibly in preparation of potential injury), increasing the likelihood of an artery-clogging blood clot.
Stress appears to impair the clearance of fat molecules in the body, raising blood-cholesterol levels, at least temporarily.
Stress that leads to depression appears to be associated with increased intima-medial thickness, a measure of the arteries that signifies worsening blood vessel disease.
Chronic stress may lead to the production of immune factors called cytokines, although study results vary widely. Cytokines produce an inflammatory response that is now believed to be responsible for damaging the arteries. Such damage contributes to heart disease. New studies indicate that some people under stress may have increased levels of C-reactive protein (CRP), a risk marker for heart attack. Each 1 mg/L increase in CRP has been linked to a 20% increased risk of myocaridal ischemia, a condition that signals poor blood flow to the heart muscle.
Stress causes the body to release inflammatory markers into the bloodstream. These markers may worsen heart disease or increase the risk of heart attack or stroke.
Studies have reported an association between stress and high blood pressure, which may be more pronounced in men than in women. According to some evidence, people who regularly experience sudden spikes in blood pressure (caused by mental stress) may, over time, develop injuries in the inner lining of their blood vessels. In one 20-year study, for example, men who periodically measured highest on the stress scale were twice as likely to have high blood pressure as those with normal stress.

Evidence is still needed to confirm any clear-cut relationship between stress and heart disease. For example, a 2002 study in Scotland found no greater risk for actual heart disease or heart events even in men who reported higher mental stress. In fact, higher stress was associated with fewer heart events. Men with high stress levels did tend to complain of chest pain and to go to the hospital for it more often than those with lower stress. They also went to the hospital more often.

Evidence links stress to heart disease in men, particularly in work situations where they lack control. The association between stress and heart problems in women is weaker, and there is some evidence that the ways women cope with stress may be more heart-protective. In one study, men were more apt than women to use alcohol or eat less healthily in response to stress, which might account for their higher heart risks from stress. Different stressors may affect genders differently. In one study, work stress was associated with a higher risk for heart disease in men, but marital stress -- not work stress -- was associated with more severe heart disease in women with existing heart problems.

A condition called stress cardiomyopathy (or Takotsubo cardiomyopathy) is widely recognized. In this disease, intense emotional or physical stress causes severe but reversible heart dysfunction. The patient experiences chest pain, and EKGs and echocardiograms indicate a heart attack, but further tests show no underlying obstructive coronary artery disease.

Acute emotional stress can create abnormal heartbeats. MRI studies show that asymmetric brain activity may play a role in making a stressed heart susceptible to ventricular arrhythmias by creating electrical instability. In some patients, this can cause sudden cardiac death.

Psychological stress is also recognized as a possible cause of acute coronary syndrome (ACS), a collection of symptoms that signify heart attack or approaching heart attack. In one study of men who suffered ACS at work or up to 2 hours after work, many of the men were found to have anger and negative emotions. A 2007 review of studies on blood qualities, coagulation, fibrinolysis, and platelet reactivity found that high levels of psychological stress are associated with harmful changes to the blood. The research suggests that stress has the potential to trigger ACS, particularly in patients with heart disease. The studies also suggest that the risk is greatest immediately after the stressful incident, rather than during it.

Stress Reduction and Heart Disease. Studies suggest that treatments that reduce psychological distress improve long-term outlook in people with heart disease, including after a heart attack. Evidence indicates that stress management programs may reduce the risk of heart attacks by up to 75% in people with heart disease. Specific stress management techniques may help some problems but not others. For example, acupuncture in one study helped people with heart failure but had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure.

One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure.

Chronic stress affects the immune system in complicated ways, and may have various results.

Susceptibility to Infections. Chronic stress appears to blunt the immune system's response to infections, and may even impair a person's response to immunizations. Several studies have shown that people under chronic stress have low white blood cell counts and are vulnerable to colds. Once a person catches a cold or flu, stress can make symptoms worse. People who carry the herpes virus or HIV may be more susceptible to viral activation following exposure to stress. Even more serious, some research has found that HIV-infected men with high stress levels progress more rapidly to AIDS when compared to those with lower stress levels.

Inflammatory Response. Some evidence suggests that chronic stress triggers an over-production of certain immune factors called cytokines. In excess levels, these chemicals can have very damaging effects. A recent study found that students unable to cope with stress had high levels of TNF-alpha, an inflammatory cytokine. Such findings may partly explain the association between chronic stress and numerous diseases, including heart disease and asthma.

Whether or not stress causes or aggravates cancer is not entirely clear. One study reported no association between stressful life events and recurrence in women who had been treated for breast cancer. Nevertheless, some animal studies suggest that lack of control over stress (not simply stress itself) had negative effects on immune function and contributed to tumor growth.

That being said, a 2007 study found that stress activates a gene that may cause metastatic cancer, as measured by increasing levels of the marker AGR2.

Although stress reduction techniques have no effect on survival rates, studies show that they are very helpful in improving a cancer patient's quality of life. Stress is also known to be one cause of hyponatremia (low plasma sodium levels) in cancer patients. Fortunately, this imbalance can be corrected with drugs called AVP-receptor agonists, developed for use in heart failure.

The brain and intestines are strongly related, and are controlled by many of the same hormones and parts of the nervous system. Indeed, some research suggests that the gut itself has features of a primitive brain. It is not surprising then that prolonged stress can disrupt the digestive system, irritating the large intestine and causing diarrhea, constipation, cramping, and bloating. Excessive production of digestive acids in the stomach may cause a painful burning.

Irritable Bowel Syndrome. Irritable bowel syndrome (or spastic colon) is strongly related to stress. With this condition, the large intestine becomes irritated, and its muscular contractions are spastic rather than smooth and wave-like. The abdomen is bloated, and the patient experiences cramping and alternating periods of constipation and diarrhea. Sleep disturbances due to stress can make irritable bowel syndrome even worse.

Peptic Ulcers. It is now well-established that most peptic ulcers are either caused by the H. pylori bacteria or the use of nonsteroidal anti-inflammatory (NSAID) medications (such as aspirin and ibuprofen). Nevertheless, studies still suggest that stress may predispose someone to ulcers, or sustain existing ulcers. Some experts estimate that social and psychological factors play some contributing role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. In any case, some experts believe that the anecdotal relationship between stress and ulcers is so strong that attention to psychological factors is still warranted.

Inflammatory Bowel Disease. Although stress is not a cause of inflammatory bowel disease (Crohn's disease or ulcerative colitis), there are reports of an association between stress and symptom flare-ups. One study, for example, found that while short-term (over the previous month) stress did not significantly exacerbate ulcerative colitis symptoms, long-term perceived stress tripled the rate of flare-ups compared to patients who did not report feelings of stress.

Stress can have varying effects on eating problems and weight.

Weight Gain. Often stress is related to weight gain and obesity. Many people develop cravings for salt, fat, and sugar to counteract tension. As a result, they gain weight. Weight gain can occur even with a healthy diet, however, in some people exposed to stress. In addition, the weight gained is often abdominal fat, a predictor of diabetes and heart problems.

The release of cortisol, a major stress hormone, appears to encourage abdominal fat and may be the primary connection between stress and weight gain. Cortisol is a glucocorticoid. These hormones, along with insulin, appear to be responsible for stress-related food cravings. A 2005 study showed that hormonally induced cravings for "comfort foods" may have a biological benefit for managing stress. Eating comfort foods appears to reduce the negative hormonal and behavioral changes associated with stress, which might lessen the impact of stress on an individual. Carbohydrates in particular have been found to significantly increase levels of tryptophan and large neutral amino acids. This produces serotonin, which improves mood and performance under stress.

A 2007 study proposes a "reward-based stress eating" model. In this theory, stress and tasty, high-calorie foods cause the brain to make chemicals called endogenous opioids. These neurotransmitters help protect against the harmful effects of stress by slowing activity of a brain process called the hypothalamic-pituitary-adrenal (HPA) axis, thus weakening the stress response. Repeated stimulation of the reward pathways through stress-induced HPA stimulation, eating tasty food, or both, may lead to changes in the brain that cause compulsive overeating.

Weight Loss. Some people suffer a loss of appetite and lose weight during periods of stress. In rare cases, stress may trigger hyperactivity of the thyroid gland, stimulating appetite but causing the body to burn up calories at a faster than normal rate.

Eating Disorders. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Some studies, however, have not found any strong link between stress and eating disorders. More work is needed to determine if changes in stress hormones are a cause or result of eating disorders.

Chronic stress has been associated with the development of insulin resistance, a condition in which the body is unable to use insulin effectively to regulate glucose (blood sugar). Insulin resistance is a primary factor in diabetes. In the Healthy Women Study, a large population of healthy women was studied for 15 years. Very stressful life events and severe depression greatly increased the risk of developing insulin resistance.

In another study of more than 33,000 Swedish workers, the development of type 2 diabetes was strongly correlated with work stress and low emotional support. However, the effect was seen in women, but not in men.

Stress can also exacerbate existing diabetes by impairing the patient's ability to manage the disease effectively.

Researchers are attempting to find the relationship between pain and emotion, but the area is complicated by many factors, including effects of personality types, fear of pain, and stress itself. A recent study suggests that chronic pain may impair the action of neutrophils, thereby weakening the immune response.

Muscular and Joint Pain. Stress may intensify chronic pain caused by arthritis and other conditions. According to a study on patients with rheumatoid arthritis, however, stress management techniques do not appear to have much effect on arthritic pain. Psychological distress also plays a significant role in the severity of back pain. Some studies have clearly associated job dissatisfaction and depression to back problems, although it is still unclear if stress is a direct cause of the back pain.

Headaches. Tension-type headaches are highly associated with stress and stressful events. Sometimes the headache does not start until long after the stressful event has ended. Additionally, stress can contribute to the development of headaches or cause headaches to occur more often.

Some research suggests that people who suffer from tension-type headaches may have some biological predisposition for translating stress into muscle contractions. Among the wide range of possible migraine triggers is emotional stress (although the headaches often erupt after the stress has eased). One study suggested that women with migraines tend to have personalities that over-respond to stressful situations.

The tensions of unresolved stress frequently cause insomnia, generally keeping the stressed person awake or causing awakening in the middle of the night or early morning. This appears to be due to the fact that stress causes physiological arousal during non-rapid eye movement (NREM) sleep.

Sexual Function. Stress can lead to diminished sexual desire and an inability to achieve orgasm in women. Stress response can cause androgen levels to drop, causing temporary impotence in men. Part of the stress response involves the release of brain chemicals that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis, which can prevent erection.

Premenstrual Syndrome. Some studies indicate that the stress response in women with premenstrual syndrome may be more intense than in those without the syndrome.

Fertility. Stress may even affect fertility. Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated cortisol levels can even shut down menstruation. One small study reported a significantly higher incidence of pregnancy loss in women who had both high stress and prolonged menstrual cycles. Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

Effects on Pregnancy. Old wives' tales about a pregnant woman's emotions affecting her baby may have some credence. Stress may cause physiologic alterations, such as increased adrenal hormone levels or resistance in the arteries, which may interfere with normal blood flow to the placenta. Maternal stress during pregnancy has been linked to a higher risk for miscarriage, lower birth weights, and increased incidence of premature births. Some evidence also suggests that stress experienced by expectant mothers can even influence the way in which the baby's brain and nervous system will react to stressful events. Indeed, one study found a higher rate of crying and low attention in infants of mothers who had been stressed during pregnancy.

Menopause. A drop in estrogen levels during perimenopause and menopause may be responsible for changes in mood precipitated by stress. Estrogen replacement therapy can soften this response to stressful events.

Stress affects the brain, particularly memory, but the effects vary widely depending on whether the stress is acute or chronic.

Effect of Acute Stress on Memory and Concentration. Studies indicate that the immediate effect of acute stress impairs short-term memory, particularly verbal memory. On the plus side, high levels of stress hormone during short-term stress have been associated with enhanced memory storage and greater concentration on immediate events. The difference in effect may be due to how cortisol impacts glucocorticoid receptors in the hippocampus and prefrontal cortex. In a study of 20 men and 20 women, those whose cortisol levels increased in response to unpleasant, emotionally arousing photos had less memory recall later than those whose cortisol levels did not rise.

Effect of Chronic Stress on Memory. If stress becomes chronic, sufferers often experience loss of concentration at work and home, and they may become inefficient and accident-prone. In children, the physiologic responses to chronic stress can clearly inhibit learning. Chronic stress in older people may play an even more important role in memory loss than the aging process. In one study, for example, older adults with low stress hormone levels tested as well as younger adults in cognitive tests; those with higher stress levels tested 20 - 50% lower.

Studies have connected long-term exposure to excess amounts of cortisol (a major stress hormone) to shrinking of the hippocampus, the brain’s memory center. For example, two studies reported that groups who suffered from post-traumatic stress disorder (Vietnam veterans and women who suffered from sexual abuse) displayed up to 8% shrinking of the hippocampus. It is not yet known if this shrinking is reversible.

Allergies. Stress has been related to skin allergies. Some research suggests that stress, not indoor pollutants, may actually be a cause of the so-called sick-building syndrome. Sick-building syndrome produces allergy-like symptoms, such as eczema, headaches, asthma, and sinus problems, in office workers.

Compulsive Hoarding. People with obsessive-compulsive disorder (OCD) and compulsive hoarding are far more likely to have experienced a traumatically stressful event than people with OCD who are not hoarders. Hoarders who have experienced traumatic events have significantly more severe hoarding than those who have not been traumatized. The strongest association with traumatic stress is found in the clutter factor of compulsive hoarding, rather than in difficulty discarding objects.

Chronic Fatigue. Stress increases the risk of developing chronic fatigue syndrome, although studies suggest that high levels of emotional instability may genetically predispose someone to the syndrome.

Skin Disorders. Stress plays a role in worsening numerous skin conditions, including hives, psoriasis, acne, rosacea, and eczema, and is one of the most common causes of eczema. Unexplained itching may also be caused by stress. Evidence suggests that experiencing the stress of a traumatic event (parental divorce or separation, or a severe disease in a family member) before age 2 increases the risk of developing eczema.

Unexplained Hair Loss (Alopecia Areata). Alopecia areata is hair loss that occurs in localized (individual) patches. The cause is unknown, but stress is suspected as a player in this condition. For example, hair loss often occurs during periods of intense stress, such as mourning.

Teeth and Gums. Stress has now been implicated in increasing the risk for periodontal disease, which is disease in the gums that can cause tooth loss.

People under chronic stress often turn to alcohol abuse or tobacco use for relief. The damage these self-destructive habits cause under ordinary circumstances is compounded by the physiological effects of stress itself. Many people also resort to abnormal eating patterns or passive activities, such as watching television. The results of a national survey, released in February 2006, show that: "Americans engage in unhealthy behaviors such as comfort eating, poor diet choices, smoking and inactivity to help deal with stress."

Alcohol affects receptors in the brain that reduce stress. Lack of nicotine increases stress in smokers, which creates a cycle of dependency on smoking. One study indicated that nicotine has calming effects in women but not in men. In fact, in the study, smoking increased aggression in men.

The cycle is self-perpetuating: a sedentary routine, an unhealthy diet, alcohol abuse, and smoking all promote heart disease. They also interfere with sleep patterns, and lead to increased rather than reduced tension levels. Drinking four or five cups of coffee, for example, can cause changes in blood pressure and stress hormone levels similar to those produced by chronic stress. Animal fats, simple sugars, and salt are known contributors to health problems.

Conditions with Similar Symptoms

The physical symptoms of anxiety disorders mirror many symptoms of stress, including:

A fast heart rate
Rapid, shallow breathing
Increased muscle tension

Anxiety is an emotional disorder, however, and is characterized by feelings of apprehension, uncertainty, fear, or panic. Unlike stress, the triggers for anxiety are not necessarily or even usually associated with specific stressful or threatening conditions. Some individuals with anxiety disorders have numerous physical complaints, such as headaches, gastrointestinal disturbances, dizziness, and chest pain. Severe cases of anxiety disorders are debilitating, and interfere with career, family, and social spheres.

Depression can be a disabling condition, and, like anxiety disorders, may result from chronic stress. A 2005 study of Canadian workers found that individuals with a high level of work-related stress are more than twice as likely to experience a major depressive episode, compared with people under less stress. Evidence also suggests that certain people may be genetically susceptible to depression after stressful life events. Depression also mimics some of the symptoms of stress, including changes in appetite, sleep patterns, and concentration. Serious depression, however, is distinguished from stress by feelings of sadness, hopelessness, loss of interest in life, and, sometimes, thoughts of suicide. Acute depression is also accompanied by significant changes in the patient's functioning. Professional therapy may be needed in order to determine if depression is caused by stress, or if it is the primary problem.

Post-traumatic stress disorder (PTSD) is a reaction to a very traumatic event, and it is actually classified as an anxiety disorder. The event that brings on PTSD is usually outside the norm of human experience, such as intense combat or sexual assault. The patient struggles to forget the traumatic event and frequently develops emotional numbness and event-related amnesia. Often, however, there is a mental flashback, and the patient re-experiences the painful circumstance in the form of dreams and disturbing thoughts and memories. These thoughts and dreams resemble or recall the trauma. Other symptoms may include lack of pleasure in formerly enjoyed activities, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle-response to noise.

Treatment

Perhaps the best general approach for treating stress can be found in the elegant passage by Reinhold Niebuhr, "Grant me the courage to change the things I can change, the serenity to accept the things I can't change, and the wisdom to know the difference." The process of learning to control stress is life-long, and will not only contribute to better health, but a greater ability to succeed in one's own agenda.

Stress can be a factor in a variety of physical and emotional illnesses, which should be professionally treated. Many stress symptoms are mild and can be managed by over-the-counter medications (for example, aspirin, acetaminophen, or ibuprofen for tension headaches; antacids, anti-diarrhea medications, or laxatives for mild stomach distress). A physician should be consulted, however, for physical symptoms that are out of the ordinary, particularly those that get worse or wake a person up at night. A mental health professional should be consulted for unmanageable acute stress or for severe anxiety or depression. Often short-term therapy can resolve stress-related emotional problems.

In choosing specific strategies for treating stress, several factors should be considered.

No single method is always successful: A combination of approaches is generally most effective.
What works for one person does not necessarily work for someone else.
Stress can be positive as well as negative. Appropriate and controllable stress provides interest and excitement and motivates the individual to greater achievement. A lack of stress may lead to boredom and depression.

Stress may play a part in making people vulnerable to illness. A physician or psychologist should be consulted if there are any indications of accompanying medical or psychological conditions, such as heart symptoms, significant pain, anxiety, or depression.

People often succeed in relieving stress for the short term. However, they go back to previous ways of stressful thinking and behaving because of outside pressure, long-held beliefs, or habits. The following are some obstacles to managing stress:

The fight or flight urge: The very idea of relaxation can feel threatening, because it is perceived as letting down one's guard. For example, an over-demanding boss may put a subordinate into a psychological state of fighting-readiness, even though there is no safe opportunity for the subordinate to fight back or express anger. Stress builds up, but the worker has the illusion, even subconsciously, that the stress itself is providing safety or preparedness. For this reason, the employee does nothing to correct the condition.
Many people are afraid of being perceived as selfish if they engage in stress-reducing activities that benefit only themselves. The truth is that self-sacrifice (in the form of not reducing one’s stress) may be inappropriate and even damaging, if the person making the sacrifice is unhappy, angry, or physically unwell.
Some people believe that certain emotional responses to stress, such as anger, are natural and unchangeable features of personality. Research has shown, however, that with cognitive behavioral therapy, individuals can be taught to change their emotional reactions to stressful events.

It is essential to remember that reducing stress and staying relaxed clears the mind, so it can begin appropriate actions to get rid of the stress-ridden conditions.

Although treating stress cannot cure medical problems, stress management can be a very important part of medical treatment. Specific stress reduction approaches may benefit different medical problems. For example, acupuncture in one study helped reduce harmful heart muscle actions in people with heart failure, but it had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure. Stress reduction may improve well-being and quality of life for many patients who are experiencing stress because of severe or chronic medical conditions.

Important Note: Never use stress reduction techniques as the only treatment, or in place of proven treatments, for any medical condition.

Risk Factors

At some point in their lives virtually everyone will experience stressful events or situations that overwhelm their natural coping mechanisms. In one poll, 89% of respondents indicated that they had experienced serious stress in their lives. Some people are simply biologically prone to stress. Many outside factors influence susceptibility as well.

Conditions Most Likely To Produce Stress-Related Health Problems. Conditions that are most likely to be associated with stress and negative physical effects include the following:

An accumulation of persistent stressful situations, particularly those that a person cannot easily control (for example, high-pressured work plus an unhappy relationship)
Persistent stress following a severe acute response to a traumatic event (such as an automobile accident)
Acute stress accompanying serious illness, such as heart disease

Factors That Influence the Response to Stress. People respond to stress differently, depending on different factors:

Early nurturing: Abusive behavior towards children may cause long-term abnormalities in the hypothalamus-pituitary system, which regulates stress.
Personality traits: Certain people have personality traits that cause them to over-respond to stressful events.
Genetic factors: Some people have genetic factors that affect stress, such as having a more or less efficient relaxation response. One study found a genetic abnormality in serotonin regulation that was connected with a heightened reaction of heart rates and blood pressure in response to stress. (Serotonin is a brain chemical involved with feelings of well-being.)
Immune regulated diseases: Certain diseases that are associated with immune abnormalities (such as rheumatoid arthritis or eczema) may actually weaken a response to stress.
The length and quality of stressors: Naturally, the longer the duration and more intense the stressors, the more harmful the effects.

Individuals at Higher Risk for Stress. Studies indicate that the following people are more vulnerable to the effects of stress than others:

Older adults: As people age, achieving a relaxation response after a stressful event becomes more difficult. Aging may simply wear out the systems in the brain that respond to stress, so that they become inefficient. The elderly, too, are very often exposed to major stressors such as medical problems, the loss of a spouse and friends, a change in a living situation, and financial worries. No one is immune to stress, however, and it may simply go unnoticed in the very young and old.
Women in general and working mothers specifically: Working mothers, regardless of whether they are married or single, face higher stress levels and possibly adverse health effects, most likely because they bear a greater and more diffuse work load than men or other women. This has been observed in women in the U.S. and in Europe. Such stress may also have a domino and harmful effect on their children. It is not clear, however, if stress has the same adverse effects on women's hearts as it does on men's.
Less educated individuals.
Divorced or widowed individuals: Numerous studies indicate that unmarried people generally do not live as long as their married contemporaries.
Anyone experiencing financial strain, particularly long-term unemployed and those without health insurance.
People who are isolated or lonely.
People who are targets of racial or sexual discrimination.
People who live in cities.

Children are frequent victims of stress because they are often unable to communicate their feelings accurately. They also have trouble communicating their responses to events over which they have no control. Certain physical symptoms, notably repeated abdominal pain without a known cause, may be indicators of stress in children.

Various conditions can affect their susceptibility to stress.

Low Birth Weight. One study reported that low birth weight and slow growth up until age 7 was related to stress in adulthood.

Parental Stress. Parental stress, especially in mothers, is a particularly powerful source of stress in children, even more important than poverty or overcrowding. In a 2002 study, for example, young children of mothers who were highly stressed (particularly if they were depressed) tended to be at high risk for developing stress-related problems. This was especially true if the mothers were stressed during both the child's infancy and early years. Some evidence even supports the old idea that stress during pregnancy can have adverse effects on the infant's mood and behavior. Older children with stressed mothers may become aggressive and anti-social. One study suggested that stress-reduction techniques in parents may improve their children's behavior.

Gender Differences in Adolescent Stress. Adolescent boys and girls experience equal amounts of stress, but the source and effects may differ. Girls tend to become stressed from interpersonal situations, and stress is more likely to lead to depression in girls than in boys. For boys, however, specific events, such as changing schools or getting poor grades, appear to be the major sources of stress.

A report issued in October 2006 by the American Academy of Pediatrics recommends more unstructured play time for children. The report notes that today’s overscheduled, hurried lifestyle that many children experience is a source of stress and anxiety in some children.

In a 1999 study of 46,000 workers, health care costs were 147% higher in workers who were stressed or depressed than in others who were not. Furthermore, according to one survey, 40% of American workers describe their jobs as very stressful, making job-related stress an important and preventable health hazard.

Several studies are now suggesting that job-related stress is as great a threat to health as smoking or not exercising. Stress impairs concentration, causes sleeplessness, and increases the risk for illness, back problems, accidents, and lost time from work. Work stress can lead to harassment or even violence while on the job. At its most extreme, chronic stress places a burden on the heart and circulation that in some cases may be fatal. The Japanese even have a word for sudden death due to overwork, karoushi.

Not all work stress is harmful. However, studies suggest the following job-related stressors may increase people's -- particularly men's -- health risks:

Having no say in decisions that affect one's responsibilities
Unrelenting and unreasonable performance demands
Lack of effective communication and conflict-resolution methods among workers and employers
Lack of job security
Night-shift work, long hours, or both
Too much time spent away from home and family
Wages not matching levels of responsibility

Reducing Stress on the Job. Many institutions within the current culture, while paying lip service to stress reduction, put intense pressure on individuals to behave in ways that increase tension. Yet, there are numerous effective management tools and techniques available to reduce stress. Furthermore, treatment for work-related stress has proven benefits for both the employee and employer. In one study, at the end of 2 years, a company that instituted a stress management program saved nearly $150,000 in workers compensations costs (the cost of the program was only $6,000). Other studies have reported specific health benefits resulting from workplace stress-management programs. In one of the studies, workers with hypertension experienced reduced blood pressure after even a brief (16-hour) program that helped them manage stress behaviorally.

In general, however, few workplaces offer stress management programs, and it is usually up to the employee to find their own ways to reduce stress. Here are some suggestions:

Seek out someone in the Human Resources department or a sympathetic manager and communicate concerns about job stress. Work with them in a non-confrontational way to improve working conditions, letting them know that productivity can be improved if some of the pressure is off.
Establish or reinforce a network of friends at work and at home.
Restructure priorities and eliminate unnecessary tasks.
Learn to focus on positive outcomes.
If the job is unendurable, plan and execute a career change. Send out resumes or work on transfers within the company.
If this isn't possible, be sure to schedule daily pleasant activities and physical exercise during free time.

It may be helpful to keep in mind that bosses are also victimized by the same stressful conditions they are imposing. For example, in one study of male managers in three Swedish companies, those who worked in a bureaucracy had greater stress-related heart risks than those who worked in companies with social supports.

Caregivers of Family Members. Studies show that caregivers of physically or mentally disabled family members are at risk for chronic stress. One study reported that overall mortality rates were over 60% higher in caregivers who were under constant stress. Spouses caring for a disabled partner are particularly vulnerable to a range of stress-related health threats, including influenza, depression, heart disease, and even poorer survival rates. Caring for a spouse with even minor disabilities can induce severe stress.

Specific risk factors that put caregivers at higher risk for severe stress, or stress-related illnesses, include:

Caregiving wives: Some studies suggest that wives experience significantly greater stress from caregiving than husbands do.
Having a low income.
Being African-American: African-American people tend to be in poorer physical health, and have lower incomes, than Caucasians. They therefore face greater stress as caregivers to their spouses than their white counterparts.
Living alone with the patient.
Helping a highly dependent patient.
Having a difficult relationship with the patient.

Intervention programs that are aimed at helping the caregiver approach the situation positively can reduce stress, and help the caregiver maintain a positive attitude. A 2002 program also demonstrated that moderate-intensity exercise was very helpful in reducing stress and improving sleep in caregivers.

Health Professional Caregivers. Caregiving among the health professionals is also a high risk factor for stress. One study, for example, found that registered nurses with low job control, high job demands, and low work-related social support experienced very dramatic health declines, both physically and emotionally.

People who are less emotionally stable or have high anxiety levels tend to experience specific events as more stressful than others. Some doctors describe an exaggerated negative response to stress as "catastrophizing" the event (turning it into a catastrophe). Nevertheless, a 2003 study of patients with anxiety disorder did not find any differences in actual physical response to stress (heart rate, blood pressure, release of stress hormones) compared to people without anxiety.

The lack of an established network of family and friends predisposes one to stress disorders and stress-related health problems, including heart disease and infections. A study, meanwhile, reported that older people who maintain active relationships with their adult children are buffered against the adverse health effects of chronic stress-inducing situations, such as low income or lower social class. Another study suggested this may be because people who live alone are unable to discuss negative feelings as a means to relieve their stress.

Studies of people who remain happy and healthy despite many life stresses conclude that most have very good networks of social support. One study indicated that support even from strangers reduced blood pressure surges in people undergoing a stressful event. Many studies suggest that having a pet helps reduce medical problems aggravated by stress, including heart disease and high blood pressure.

Lifestyle Changes

A healthy lifestyle is an essential companion to any stress-reduction program. General health and stress resistance can be enhanced by regular exercise, a diet rich in a variety of whole grains, vegetables, and fruits, and by avoiding excessive alcohol, caffeine, and tobacco.

Of interest, a 2003 study suggested that fish oil, which has been associated with a lower risk for heart disease and stroke, may blunt some of the harmful effects of mental stress on the heart.

In one study, high doses of vitamin C reduced stress levels and blood pressure. The doses given were higher than the recommended upper limit of 2,000 mg per day. High doses may cause headaches and diarrhea. Long-term use increases risk for kidney stones and has other adverse effects in specific individuals.

Exercise in combination with stress management techniques is extremely important for many reasons:

Exercise is an effective distraction from stressful events.
Exercise may directly blunt the harmful effects of stress on blood pressure and the heart (exercise protects the heart in any case).

Usually, a varied exercise regime is more interesting, and thus easier to stick to. Start slowly. Strenuous exercise in people who are not used to it can be very dangerous and any exercise program should be discussed with a physician. In addition, half of all people who begin a vigorous training regime drop out within a year. The key is to find activities that are exciting, challenging, and satisfying. The following are some suggestions:

Sign up for aerobics classes at a gym.
Brisk walking is an excellent aerobic exercise that is free and available to nearly anyone. Even short brisk walks can relieve bouts of stress.
Swimming is an ideal exercise for many stressed people, including pregnant women, individuals with musculoskeletal problems, and those who suffer exercise-induced asthma.
Yoga or Tai Chi can be very effective, combining many of the benefits of breathing, muscle relaxation, and meditation while toning and stretching the muscles. The benefits of yoga may be considerable. Numerous studies have found it beneficial for many conditions in which stress is an important factor, such as anxiety, headaches, high blood pressure, and asthma. It also elevates mood and improves concentration and the ability to focus.

As in other areas of stress management, making a plan and executing it successfully develops feelings of mastery and control, which are very beneficial in and of themselves. Start small. Just 10 minutes of exercise three times a week can build a good base for novices. Gradually build up the length of these every-other-day sessions to 30 minutes or more.

Cognitive-behavioral techniques (CBT) are among the most effective ways of reducing stress. A 2005 study found that CBT training can have a long-term impact one’s ability to cope with stress. In the study, participants received CBT training and were exposed to a stressful situation 4 months later. The participants who had received CBT training had significantly less stress-induced cortisol responses compared with individuals who had received no stress management training. This effect was observed in both men and women, although the CBT had a greater effect on men. CBT may be particularly helpful when the source of stress is chronic pain or a chronic disease. In fact, in a study of patients with HIV, CBT was more helpful than support groups for improving well-being and quality-of-life.

A typical CBT approach includes identifying sources of stress, restructuring priorities, changing one's response to stress, and finding methods for managing and reducing stress.

Identifying Sources of Stress. One key component in most CBT approaches is a diary that keeps an informal inventory of daily events and activities. While this exercise might itself seem stress producing (and yet one more chore), it need not be done in painstaking detail. A few words accompanying a time and date are usually enough to serve as reminders of significant events or activities.

The first step is to note activities that put a strain on energy and time, trigger anger or anxiety, or precipitate a negative physical response (such as a sour stomach or headache).

Also note positive experiences, such as those that are mentally or physically refreshing or produce a sense of accomplishment.

After a week or two, try to identify two or three events or activities that have been significantly upsetting or overwhelming.

Questioning the Sources of Stress. Individuals should then ask themselves the following questions:

Do these stressful activities meet my goals or someone else's?
Have I taken on tasks that I can reasonably accomplish?
Which tasks are under my control and which ones aren't?

Restructuring Priorities: Adding Stress Reducing Activities. The next step is to attempt to shift the balance from stress-producing to stress-reducing activities. Eliminating stress is rarely practical or feasible, but there are many ways to reduce its impact.

Consider as many relief options as possible. Examples include:

Listen to music. Music is an effective stress reducer in both healthy individuals and people with health problems. In one study, for example, students who listened to a well-known gentle classical piece of music during a stressful task had reduced feelings of anxiety, heart rate, and blood pressure.
Take long weekends or, ideally, vacations.
If the source of stress is in the home, plan times away, even if it is only an hour or two a week.
Replace unnecessary time-consuming chores with pleasurable or interesting activities.
Make time for recreation. This is as essential as paying bills or shopping for groceries.
Own a pet. In a study of people with high blood pressure, pet owners had much lower blood pressure increase in response to stress than non-owners. Note that owning a pet was beneficial only for people who like animals to begin with.

Discuss Feelings. The concept of communication and letting your feelings out has been so excessively promoted and parodied that it has nearly lost its value as good psychological advice. Nevertheless, feelings of anger or frustration that are not expressed in an acceptable way may lead to hostility, a sense of helplessness, and depression.

Expressing feelings does not mean venting frustration on waiters and subordinates, boring friends with emotional minutia, or wallowing in self-pity. In fact, because blood pressure may spike when certain chronically hostile individuals become angry, some therapists strongly advise that just talking, not simply venting anger, is the best approach, especially for these people.

The primary goal is to explain and assert one's needs to a trusted individual in as positive a way as possible. Direct communication may not even be necessary. Writing in a journal, writing a poem, or composing a letter that is never mailed may be sufficient.

Expressing one's feelings solves only half of the communication puzzle. Learning to listen, empathize, and respond to others with understanding is just as important for maintaining the strong relationships necessary for emotional fulfillment and reduced stress.

Keep Perspective and Look for the Positive. Reversing negative ideas and learning to focus on positive outcomes helps reduce tension and achieve goals. The following steps, using an example of a person who is alarmed at the prospect of giving a speech, may be useful:

First, identify the worst possible outcomes (forgetting the speech, stumbling over words, humiliation, audience contempt).
Rate the likelihood of these bad outcomes happening (probably very low or that speaker wouldn't have been selected in the first place).
Envision a favorable result (a well-rounded, articulate presentation with rewarding applause).
Develop a specific plan to achieve the positive outcome (preparing in front of a mirror, using a video camera or tape recorder, relaxation exercises).
Try to recall previous situations that initially seemed negative but ended well.

Use Humor. Research has shown that humor is a very effective mechanism for coping with acute stress. Keeping a sense of humor during difficult situations is a common recommendation from stress management experts. Laughter not only releases the tension of pent-up feelings and helps keep perspective, but it appears to have actual physical effects that reduce stress hormone levels. It is not uncommon for people to recall laughing intensely even during tragic events, such as the death of a loved one, and to remember this laughter as helping them to endure the emotional pain.

Relaxation Methods. Since stress is here to stay, everyone needs to develop methods to promote the relaxation response, the natural unwinding of the stress response. Relaxation lowers blood pressure, respiration, and pulse rates, releases muscle tension, and eases emotional strains. This response is highly individualized, but there are certain approaches that seem to work.

Combinations are probably best. For example, in a study of children and adolescents with adjustment disorder and depression, a combination of yoga, a brief massage, and progressive muscle relaxation effectively reduced both feelings of anxiety and stress hormone levels. A 2005 study of organ transplant recipients showed that training in meditation and gentle yoga led to significant improvements in quality of sleep and lessened anxiety and depression.

No one should expect a total resolution of stress from these approaches, but if done regularly, these programs can be very effective.

Acupuncture. Some evidence suggests that acupuncture may also be helpful. It might even improve some physical factors associated with stress and health problems. For example, in a study of heart failure patients, acupuncture improved stress-related heart muscle activity, which could be an important benefit in these patients. However, acupuncture had no effect on stress-related blood pressure or heart rate.

Hypnosis. Hypnosis may also benefit some people with severe stress. In one study of patients with irritable bowel, stress reduction by hypnosis correlated with improvement in many bowel symptoms.


*Deep Breathing Exercises.* During stress, breathing becomes shallow and rapid. Taking a deep breath is an automatic and effective technique for winding down. Deep breathing exercises consciously intensify this natural physiologic reaction and can be very useful during a stressful situation, or for maintaining a relaxed state during the day.	Inhale through the nose slowly and deeply to the count of 10. Make sure that the stomach and abdomen expand, but the chest does not rise. Exhale through the nose, slowly and completely, also to the count of 10. To help quiet the mind, concentrate fully on breathing and counting through each cycle. Repeat five to 10 times, and make a habit of doing the exercise several times each day, even when not feeling stressed.
*Muscle Relaxation.* Muscle relaxation techniques, often combined with deep breathing, are simple to learn and very useful for getting to sleep. In the beginning it is useful to have a friend or partner check for tension by lifting an arm and dropping it. The arm should fall freely. Practice makes the exercise much more effective and produces relaxation much more rapidly. Small studies have reported beneficial effects on blood pressure in patients with high blood pressure who use this technique.	After lying down in a comfortable position without crossing the limbs, concentrate on each part of the body. Maintain a slow, deep breathing pattern throughout this exercise. Tense each muscle as tightly as possible for a count of five to 10, and then release it completely. Experience the muscle as totally relaxed and lead-heavy. Begin with the top of the head and progress downward to focus on all the muscles in the body. Be sure to include the forehead, ears, eyes, mouth, neck, shoulders, arms and hands, fingers, chest, belly, thighs, calves, and feet. Once the external review is complete, imagine tensing and releasing internal muscles.
*Meditation.* Meditation, used for many years in Eastern cultures, is now widely accepted in this country as a relaxation technique. The goal of all meditative procedures, both religious and therapeutic, is to quiet the mind (essentially, to relax thought). Small studies have suggested that regular meditation can benefit the heart and help reduce blood pressure. Better research is needed, however, to confirm such claims. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in early evening before dinner. Even once a day is helpful. Note: Meditating before going to bed may cause some people to wake up in the middle of the night, alert and unable to return to sleep. New practitioners should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Several techniques are available. A few are discussed here. The only potential risks from meditating are in people with psychosis, in whom meditating may trigger a psychotic event.	Mindfulness Meditation. Mindfulness is a common practice that focuses on breathing. It employs the basic technique used in other forms of meditation. Sit upright with the spine straight, either cross-legged or sitting on a firm chair with both feet on the floor, uncrossed. With the eyes closed or gently looking a few feet ahead, observe the exhalation of the breath. As the mind wanders, simply note it as a fact and returns to the "out" breath. It may be helpful to imagine your thoughts as clouds dissipating away. Transcendental Meditation (TM). TM uses a mantra (a word that has a specific chanting sound but no meaning). The person meditating repeats the word silently, letting thoughts come and go. In one study, TM was as effective as exercise in elevating mood. Mini-Meditation. The method involves heightening awareness of the immediate surrounding environment. Choose a routine activity when alone. For example: While washing dishes, concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience (sounds outside the window, smells from the stove, colors in the room). If the mind begins to think about the past or future, or fills with unformed thoughts or worries, redirect it gently back. This redirection of brain activity from your thoughts and worries to your senses disrupts the stress response and prompts relaxation. It also helps promote an emotional and sensual appreciation of simple pleasures already present in a person's life.
*Biofeedback.* Biofeedback is a technique that measures bodily functions, like breathing, heart rate, blood pressure, skin temperature, and muscle tension. By watching these measurements, you can learn how to alter these functions by relaxing or holding pleasant images in your mind.	During biofeedback, electric leads are taped to a subject's head. The person is encouraged to relax using methods such as those described above. Brain waves are measured and an audible signal is emitted when alpha waves are detected, a frequency which coincides with a state of deep relaxation. By repeating the process, subjects associate the sound with the relaxed state and learn to achieve relaxation by themselves.
*Massage Therapy.* A 2005 report that reviewed data from multiple studies showed that massage therapy decreases cortisol levels. Another 2005 study showed that massage from a stable romantic partner can reduce physiological responses to a subsequent stressful event. In the study, women who received instructed shoulder-neck-massage from their partners before being exposed to stress had lowered cortisol responses, and smaller heart rate increases after the stressful event. Interestingly, massage was more beneficial than receiving social support from the partner, indicating the power of physical touch in managing stress. Several massage therapies are available.	Many massage techniques are available, such as the following: Swedish massage is the standard massage technique. It uses long smooth strokes, and kneading and tapping of the muscles. Shiatsu applies intense pressure to the same points targeted in acupuncture. It can be painful, but people report deep relaxation afterward. Reflexology manipulates acupuncture points in the hands and feet.

Some people who experience chronic stress seek herbal or natural remedies. It should be strongly noted, however, that just as with standard drugs, so-called natural remedies can cause problems, sometimes serious ones.

Probiotics. Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria. They do so through various mechanisms, such as excreting certain acids (for example, lactate, acetate) that inhibit harmful bacteria. They may also compete with them for nutrients. Stress reduces levels of these bacteria. Research even suggests that probiotics may help maintain remission in patients with IBD. In one small study, people suffering from stress and exhaustion significantly reduced their stress symptoms and gastrointestinal complaints when they took a probiotic supplement for 6 months. The specific bacteria that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Aromatherapy. The smell of lavender has long been associated with a calming effect. In a Japanese study, 14 women who were put in a room with a lavender scent experienced reduced mental stress. Several aromatherapies are now used for relaxation. Use caution, however, as some of the exotic plant extracts in these formulas have been associated with a wide range of skin allergies.

Valerian. Valerian is an herb that has sedative qualities and may reduce stress and associated physical effects. This herb is on the FDA's list of generally safe products. Of note, however, the herb's effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. Side effects include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, however, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been numerous reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Special Warning on Kava. Kava has been commonly used to reduce anxiety and stress. It is now highly associated with liver injury and even liver failure in a few cases. Experts now strongly warn against its use.

People seeking relief from stress should be wary of things that promise a quick cure, or plans that include the purchase of expensive treatments. These treatments may be useless and sometimes even dangerous.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.nami.org -- National Alliance for the Mentally Ill
www.nmha.org -- National Mental Health Association
www.amtamassage.org -- American Massage Therapy Association
www.cognitivetherapynyc.com -- American Institute for Cognitive Therapy
www.aabt.org -- Association for the Advancement of Behavior Therapy
www.healthyminds.org -- The American Psychiatric Association
www.naswdc.org -- The National Association of Social Workers
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.stress.org -- The American Institute of Stress

References

Ginsburg KR and the Committee on Communications and Committee on Psychosocial Aspects of Child and Family Health. Clinical Report: The Importance of Play in Promoting Healthy Child Development and Maintaining Strong Parent-ChildBonds.Last accessed on 17 October, 2006.

Dallman MF, Pecoraro NC, la Fleur SE. Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun. 2005;19:275-280.

Wang J. Work stress as a risk factor for major depressive episode(s). Psychol Med. 2005;35:865-871.

Hammerfald K, Grau M, et al. Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects-A randomized controlled trial. Psychoneuroendocrinology. 2005 Sep 22; epub ahead of print.

Kreitzer MJ, Gross CR, Ye X, et al. Longitudinal impact of mindfulness meditation on illness burden in solid-organ transplant recipients. Prog Transplant. 2005;15:166-172.

Field T, Hernandez-Reif M, Diego M, et al. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci. 2005;115:1397-1413.

Ditzen B, Neumann I, Bodenmann G, et al. Romantic Partner Interaction Reduces Endocrine and Autonomic Stress Responses in Women. New Research Abstracts, Annual Meeting of the American Psychiatric Association. Washington, D.C. 2005. Abstract NR140.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Stroke

FitSugar — Wed, 08 Oct 2008 17:35:08 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Prognosis
Prevention
Diagnosis
Managing a Stroke
Medications
Surgery
Recovery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Statin Drug Approved for Stroke Prevention

In 2007, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risk of stroke in patients with heart disease.
High-dose atorvastatin may help reduce the risk of recurrent stroke in patients who have had a recent stroke or transient ischemic attack, according to a New England Journal of Medicine study.

Drug Warnings

In 2006, the FDA strengthened the warning label for the anticoagulant drug warfarin (Coumadin) to emphasize its bleeding risks. However, warfarin is still the gold standard treatment for most patients with atrial fibrillation.
Evidence suggests that people at risk for stroke should avoid taking non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil) and diclofenac (Cataflam). COX-2 inhibitors should only be used as a last resort for pain relief. Try non-drug treatments (physical therapy, hot/cold compresses) first.

Aspirin

In 2007, the American Heart Association (AHA) issued new heart disease prevention guidelines for women. The AHA recommends low-dose aspirin therapy for women over age 65 who are at risk for stroke.
The combination of aspirin and dipyridamole (Aggrenox) may be better than aspirin alone in preventing major stroke in patients who have had a minor stroke, suggests a Lancet study.

Diagnosis

Magnetic resonance imaging (MRI) is better than computed tomography (CT) in detecting whether stroke (especially ischemic stroke) has occurred, indicates an important Lancet study.

Surgery

Carotid endarterectomy appears to be superior to and safer than carotid angioplasty and stenting (CAS) for most patients with artery stenosis (narrowing) of over 60%, suggest several recent studies. Most experts recommend CAS only for patients who have severe stenosis (greater than 70%) and high surgical risk.

Rehabilitation

Constraint-induced movement therapy (CIMT) may help patients who have recently had a stroke regain use of a paralyzed arm. The technique involves repetitive motion exercises while restraining the less functional arm.

Introduction

Blood Flow Blockage. The brain receives about 25% of the body's oxygen, but it cannot store it. Brain cells require a constant supply of oxygen to stay healthy and function properly. Therefore, blood needs to be supplied continuously to the brain through two main arterial systems:

The carotid arteries come up through either side of the front of the neck. (To feel the pulse of a carotid artery, place your fingertips gently against either side of your neck, right under the jaw.)
The basilar artery forms at the base of the skull from the vertebral arteries, which run up along the spine, join, and come up through the rear of the neck.

The Circle of Willis is the joining area of several arteries at the bottom (inferior) side of the brain. At the Circle of Willis, the internal carotid arteries branch into smaller arteries that supply oxygenated blood to over 80% of the cerebrum.

A reduction of, or disruption in, blood flow to the brain is the primary cause of a stroke. Blockage for even a short period of time can be disastrous and cause brain damage or even death.

Click the icon to see an image of the brain.

A stroke is usually defined as two types:

Ischemic (caused by a blockage in an artery)
Hemorrhagic (caused by a tear in the artery's wall that produces bleeding in the brain)

The consequences of a stroke, the type of functions affected, and the severity, depend on where in the brain it has occurred and the extent of the damage.

Ischemic strokes are by far the more common type, causing over 80% of all strokes. Ischemia means the deficiency of oxygen in vital tissues. Ischemic strokes are caused by blood clots that are usually one of three types:

Thrombotic stroke
Embolic stroke
Lacunar stroke

Thrombotic or Large-Artery Stroke and Atherosclerosis. The thrombotic stroke accounts for about 60% of all strokes. It usually occurs when an artery to the brain is blocked by a thrombus (blood clot) that forms as the result of atherosclerosis (commonly known as hardening of the arteries). These strokes are also sometimes referred to as large-artery strokes. The process leading to thrombotic stroke is complex and occurs over time:

The arterial walls slowly thicken, harden, and narrow until blood flow is reduced, a condition known as stenosis.
These now abnormal arteries become vulnerable to injury. Such injuries signal the immune system to release white blood cells (particularly those called neutrophils and macrophages) at the site. This process is the first step in the inflammatory response, which may play a significant role in the stroke.
Macrophages literally "eat" foreign debris and become foamy cells that attach to smooth muscle cells of blood vessels, causing them to build up.
The immune system, sensing further harm, releases other factors called cytokines, which attract more white blood cells and perpetuate the whole cycle.

As these processes continue, blood flow slows. In addition, other events contribute to the coming stroke:

The injured inner walls fail to produce enough nitric oxide, a substance critical for maintaining blood vessel elasticity. The arteries become calcified and lose elasticity.
The arteries, now hardened and rigid, become susceptible to tearing. In this event, the thrombus (blood clot) forms.
The blood clot then blocks the already narrowed artery and shuts off oxygen to part of the brain. A stroke occurs.

Embolic Strokes and Atrial Fibrillation. An embolic stroke is usually caused by a dislodged blood clot that has traveled through the blood vessels (an embolus) until it becomes wedged in an artery. Embolic strokes account for about 25% of all strokes and may be due to various conditions:

In about 15% of embolic strokes, the blood clots originally form as a result of a rhythm disorder known as atrial fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart (the atria). Because of the irregular pumping, some blood may remain in the heart chamber where it forms clots, which can then break off and travel to the brain as emboli.
Emboli can originate from blood clots that form at the site of artificial heart valves or as a result of heart valve disorders.
Emboli can also occur after a heart attack or in association with heart failure.
Rarely, emboli are formed from fat particles, tumor cells, or air bubbles that travel through the bloodstream.

Lacunar Strokes. Lacunar infarcts are a series of very tiny, ischemic strokes, which cause clumsiness, weakness, and emotional variability. They are actually a subtype of thrombotic stroke and constitute about 38% of this major group. In some populations, such as among Japanese, they are the most common stroke subtypes. They can also sometimes serve as warning signs for a major stroke.

Silent Brain Infarctions. Many elderly people have silent brain infarctions, small strokes that cause no apparent symptoms. They are detected in between 10 - 38% of elderly patients who undergo imaging tests for problems other than stroke. A 2002 study suggested that they double the risk for future stroke. They also may be major contributors to mental impairment in the elderly. Smokers and people with hypertension are at particular risk.

Transient ischemic attacks (TIAs) are mini-ischemic strokes, usually caused by tiny emboli (clots often formed of pieces of calcium and fatty plaque) that lodge in an artery to the brain. They typically break up quickly and dissolve but they do temporarily block the supply of blood to the brain. The mental or physical disturbances resulting from TIAs generally clear up in less than a day, with nearly all symptoms resolving in less than an hour.

However, experts now advise that a TIA should be taken very seriously and treated as aggressively as a stroke. Both stroke and TIA increase the risk for a subsequent stroke. Moreover, the risk for having another stroke can be as high as 40% within 5 years. The American Heart Association/American Stroke Association recommends these guidelines to prevent a second stroke after TIA:

Lifestyle changes.

Stop smoking
Limit alcohol
Increase exercise (30 minutes a day of moderate physical activity)
Lose excess weight (waist measurements should be no more than 35 inches for women and 40 inches for men; body mass index should be 18.5 - 24.9)

Drug treatments.

Drugs to control cholesterol, high blood pressure, and (for people with diabetes) high blood sugar levels
Antiplatelet therapy such aspirin, dipyridamole, or clopidogrel)

Surgery.

Carotid endarterectomy surgery or carotid artery stenting is recommended for patients with severe (70% or more) carotid stenosis (narrowing or blockage of one or both arteries in the neck)
Endarterectomy or stenting may also be appropriate for some patients with moderate stenosis (50 - 69%)
Endarterectomy and stents are not needed for patients with mild stenosis (less than 50%)

Over 15% of strokes occur from hemorrhage (sudden bleeding) in the brain. In a healthy brain, brain cells called neurons are protected from exposure to blood by the blood-brain barrier, a wall of tiny vessels and structural cells. In a hemorrhagic stroke, however, this barrier is broken.

Hemorrhagic strokes may be categorized by how and where they occur.

Parenchymal, or cerebral, hemorrhage strokes. These strokes occur within the brain and account for about 10% of all strokes. They are most often the result of hypertension exerting excessive pressure on arterial walls already damaged by atherosclerosis. Heart attack patients who have been given drugs to break up blood clots or blood-thinning drugs have a slightly elevated risk of this type of stroke.
Subarachnoid hemorrhagic strokes. This other major hemorrhagic stroke accounts for about 5% of all strokes. This kind of stroke occurs when a blood vessel on the surface of the brain bursts, leakign blood into the subarachnoid space, an area between the brain and the skull. They are usually caused by the rupture of an aneurysm, a weakening in the blood vessel wall, which is often an inherited trait.
Arteriovenous malformation (AVM) is an abnormal connection between arteries and veins. If it occurs in the brain and ruptures, it can also cause a hemorrhagic stroke.

Symptoms

People at risk and partners or caretakers of people at risk for stroke should be aware of the general symptoms. The stroke victim should get to the hospital as soon as possible after these warning signs appear. It is particularly important for people with migraines or frequent severe headaches to understand how to distinguish between their usual headaches and symptoms of stroke.

The American Stroke Association lists the following five warning signs of stroke. PEOPLE SHOULD IMMEDIATELY CALL FOR EMERGENCY ASSISTANCE IF THEY EXPERIENCE ANY OF THESE SYMPTOMS:

Sudden numbness or weakness of the face, arm or leg, especially on one side of the body
Sudden confusion, trouble speaking or understanding
Sudden trouble seeing in one or both eyes
Sudden trouble walking, dizziness, loss of balance or coordination
Sudden, severe headache with no known cause

Research indicates that patients receive faster treatment for stroke if they arrive by ambulance rather than coming to the emergency room on their own.

An easy way to remember the signs of stroke, and what to do, is by the acronym "F.A.S.T." If you think you or someone else is having a stroke, the National Stroke Association's F.A.S.T. test advises:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

The symptoms of a transient ischemic attack (TIA) and early ischemic stroke are similar. In the case of a TIA, however, the symptoms should resolve within 24 hours. Symptoms depend on where the injury in the brain occurs. The origin of the stroke is usually either the carotid or basilar arteries.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

Symptoms From Blockage in the Carotid Arteries. The carotid arteries stem off of the aorta (the primary artery leading from the heart) and lead up through the neck around the windpipe and on into the brain. When TIAs or stroke occur from blockage in the carotid artery, which they often do, symptoms may occur in either the retina of the eye or the cerebral hemisphere (the large top part of the brain).

Symptoms include the following:

When oxygen to the eye is reduced, people describe the visual effect as a shade being pulled down. People may develop poor night vision. About 35% of TIAs are associated with temporary lost vision in one eye. Although such events are risk factors for future stroke, they pose a lower risk for a stroke and its complications than more widespread TIA symptoms.
When the cerebral hemisphere is affected, a person can experience problems with speech and partial and temporary paralysis, drooping eyelid, tingling, and numbness, usually on one side of the body. The stroke victim may be unable to express thoughts verbally or to understand spoken words. If the stroke injuries are on the right side of the brain, the symptoms will develop on the left side of the body and vice versa.
Uncommonly, patients may experience seizures.

Symptoms From Blockage in the Basilar Artery. The other major site of trouble, the basilar artery, is formed at the base of the skull from the vertebral arteries, which run up along the spine and join at the back of the head. When stroke or TIAs occur here, both hemispheres of the brain may be affected so that symptoms occur on both sides of the body. The following symptoms may develop:

Temporarily dim, gray, blurry, or lost vision
Tingling or numbness in the mouth, cheeks, or gums
Headache, usually in the back of the head
Dizziness
Nausea and vomiting
Difficulty swallowing
Weakness in the arms and legs, sometimes causing a sudden fall

Such strokes usually occur in the brain stem, which can have profound affects on breathing, blood pressure, heart rate, and other vital functions, but does not affect thinking or language.

Speed of Symptom Onset. The speed of symptom onset of a major ischemic stroke may indicate its source:

If the stroke is caused by a large embolus (a clot that has traveled to an artery in the brain), the onset is sudden. Headache and seizures can occur within seconds of the blockage.
When thrombosis (a blood clot that has formed within the brain) causes the stroke, the onset usually occurs more gradually, over minutes to hours. On rare occasions it progresses over days to weeks.

Click the icon to see an image of carotid dissection.

Click the icon to see an image of stroke.

Cerebral Hemorrhage Symptoms. Symptoms of a cerebral, or parenchymal, hemorrhage typically begin very suddenly and evolve over several hours and include:

Headache
Nausea and vomiting
Altered mental states
Seizures

Subarachnoid Hemorrhage. When the hemorrhage is a subarachnoid type, warning signs may occur from the leaky blood vessel a few days to a month before the aneurysm fully develops and ruptures. Warning signs may include:

Abrupt headaches
Nausea and vomiting
Sensitivity to light
Various neurologic abnormalities. Seizures, for example, occur in about 8% of patients.

When the aneurysm ruptures, the stroke victim may experience:

A terrible headache
Neck stiffness
Vomiting
Altered states of consciousness
Eyes may become fixed in one direction or lose vision
Stupor, rigidity, and coma

Risk Factors

New or recurrent strokes affect about 700,000 Americans every year. Although incidence of stroke has increased, more people are surviving stroke, and the death rate is declining. While age is the major risk factor, people with stroke are likely to have more than one risk factor.

Older Adults. People most at risk for stroke are older adults, particularly those with high blood pressure, who are sedentary, overweight, smoke, or have diabetes. Older age is also linked with higher rates of post-stroke dementia.

Younger Adults. Younger people are not immune, however. About 28% of stroke victims are under age 65.

In most age groups except older adults, stroke is more common in men than in women. However, it kills more women than men, regardless of ethnic groups. It is not clear why women have a higher mortality rate from stroke. The arteries that lead to the brain may be more vulnerable to the effects of plaque build-up in women than in men.

In 2007, the American Heart Association released new heart disease prevention guidelines for women. The new guidelines recommend daily aspirin therapy (75 - 325 mg/day) to help prevent stroke in high-risk women over the age of 65. For older women with a lower stroke risk, the AHA recommends 81 mg of aspirin a day or 100 mg of aspirin every other day. Aspirin does not appear to provide much stroke protection benefit for women under the age of 65.

All minority groups, including Native Americans, Hispanics, and African-Americans, face a significantly higher risk for stroke and stroke death than Caucasians. The risk is also higher in Asian Americans, although stroke rates appear to be declining in this group. The differences in risk among all groups diminish as people age.

The greatest disparity in risk occurs in young adults. Younger African-Americans are two to three times more likely to experience a stroke than their Caucasian peers and four times more likely to die from one. They also face a higher risk for death from heart disease. African-Americans have a higher prevalence of diabetes and hypertension than other groups. However, studies suggest that socioeconomic factors also affect these differences.

People in the southeastern U.S. have had the highest risk for stroke in the country for some years; those at particular risk live in North Carolina, South Carolina, and Georgia. This risk may be shifting westward. High stroke rates are also occurring in the lower Mississippi valley and in Southern California. Socioeconomic differences do not fully explain these higher-risk areas.

Heart disease and stroke are closely tied for many reasons:

Patients with one condition often have risk factors for the other, such as high blood pressure, atherosclerosis (hardening of the arteries), and diabetes.
The risk of stroke increases during surgical procedures involving the coronary arteries, including coronary bypass operations and angioplasty. Coronary bypass poses the greater risk -- about 2 - 5%.
Anti-clotting drugs used for treatment of heart disease and heart attacks slightly increase the risk for hemorrhagic stroke.
A heart attack itself poses a high risk for stroke, which, according to a major 2002 study, is 2.5% in the first 6 months and 5% per year thereafter. In the study, patients with a higher risk (about 4%) for stroke within 6 months of a heart attack tended to be older (over age 75), African-American, or to have a history of a previous stroke, atrial fibrillation, hypertension, diabetes, or peripheral artery disease. Most people at high risk have more than one of these problems.

High Blood Pressure (Hypertension). High blood pressure (known medically as hypertension ) contributes to 70% of all strokes. Researchers have estimated that controlling blood pressure can prevent nearly 40% of strokes.

Two numbers are used to describe blood pressure phases and may affect stroke risk separately:

The systolic pressure (the higher and first number) is measured as the heart contracts to pump out the blood. Evidence suggests that elevated systolic pressure poses a significant danger for heart and stroke emergencies when diastolic is normal, a condition called isolated systolic hypertension. The wider the spread between the systolic and diastolic measurements, the greater the danger.
The diastolic pressure (the lower and second number) is measured as the heart relaxes to allow blood to refill the heart between beats. Abnormally higher diastolic pressure is a strong predictor of heart attack and stroke in most people with hypertension.
Stroke from Low Blood Pressure (Hypotension). Uncommonly, blood pressure that is too low can reduce oxygen supply to the brain and cause a stroke. This can occur from a heart attack, a major bleeding episode, an overwhelming infection, or rarely, from surgical anesthesia or from over-treatment of high blood pressure.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Click the icon to see an image of the risks of untreated hypertension.

Atrial Fibrillation. About one in six strokes are due to atrial fibrillation. This is a heart rhythm disorder in which the atria (the upper chambers in the heart) beat very quickly and nonrhythmically. The blood pools instead of being pumped out, increasing the risk for formation of blood clots that break loose and travel toward the brain. Atrial fibrillation poses a six-fold increased risk for stroke and may also pose a higher risk for complications after a stroke.

Atrial fibrillation is uncommon in people under 60 years old, but about 6% of adults over age 80 have this heart rhythm disorder. In this patient group, the risk for stroke may be higher or lower with the presence of other risk factors, including having heart failure, high blood pressure, diabetes, and a previous history of stroke, TIA, or rheumatic heart disease. More women than men have AF, but risk for stroke is higher in women with this condition than in men.

Patent Foramen Ovale. Patent foramen ovale (PFO) is a flap-like opening between chambers of the heart. The foramen ovale is always open during fetal development to enhance blood flow to the fetus. It then typically closes after birth when the lungs take over. However, evidence suggests that it remains open in up to 30% of adults. In such cases, blood moves backward (right to left) through this opening when pressure in the right chamber exceeds the left. Large PFOs are a major cause of stroke, particularly in younger adults. Treatments include anti-clotting drugs and procedures for closing the opening.

Atrial Septal Aneurysm. Atrial septal aneurysm is an inborn condition in which part of the atrium (one of the heart chambers) bulges out. Studies indicate that this may pose a slight risk for stroke in young people.

People who smoke a pack a day have almost two and a half times the risk for stroke as nonsmokers. Smoking increases both hemorrhagic and ischemic stroke risk. The risk for stroke may remain elevated for as long as 14 years after quitting, so the earlier one quits the better.

Heart disease and stroke are the leading causes of death in people with diabetes. Diabetes is a strong risk factor for ischemic stroke, perhaps because of accompanying risk factors, such as obesity and high blood pressure. Diabetes does not appear to increase the risk for hemorrhagic stroke. Diabetes is second only to high blood pressure as the main risk factor for stroke. The risk is highest for adults newly diagnosed with type 2 diabetes and patients with diabetes who are younger than age 55. African-Americans with diabetes are at even higher risk for stroke at a younger age.

Studies have also implicated insulin resistance, an important disease mechanism in type 2 diabetes, as an independent factor in the development of atherosclerosis and stroke. With this condition, insulin levels are normal to high, but the body is unable to use the insulin normally to metabolize blood sugar. The body compensates by raising the level of insulin, which in turn increases the risk for blood clots and reduces HDL levels (the beneficial form of cholesterol). Some studies have also reported a worse outcome in patients whose blood sugar levels are high at the time of a stroke.

Obesity may increase the risk for both ischemic and hemorrhagic stroke independently of other risk factors that often co-exist with excess weight, including insulin resistance and diabetes, high blood pressure, and unhealthy cholesterol level. Weight that is centered around the abdomen (the so-called apple shape) has a particularly high association with stroke, as it does for heart disease, in comparison to weight distributed around hips (pear-shape).

Obesity is particularly hazardous when it is one of the components of metabolic syndrome. This syndrome is diagnosed when three of the following conditions are present: abdominal obesity, low HDL cholesterol, high triglyceride levels, high blood pressure, and insulin resistance. Because metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease, people with this syndrome are at increased risk for stroke even before diabetes develops.

Although an unhealthy balance of cholesterol and other lipids (fatty compounds) plays a major role in heart disease, its role in stroke is less clear. Different lipids may have different effects:

Ischemic Stroke. The effects of high total cholesterol and LDL levels on stroke are not clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. HDL (the so-called good cholesterol) may protect against ischemic stroke (although statins have little effect on HDL).

Hemorrhagic Stroke. HDL may reduce the risk for hemorrhagic stroke (bleeding in the brain). People with overall cholesterol levels below 180 mg/dL, however, may be at risk for hemorrhagic stroke, particularly if they also have high blood pressure. This is a far less common stroke, however, than ischemic stroke.

In any case, reducing cholesterol is extremely important in anyone with heart disease and abnormal lipid levels.

Genetics may be responsible for many of the causes of stroke. Studies indicate that a family history of stroke, particularly in one's father, is a strong risk factor for stroke.

Genetics and Subarachnoid Hemorrhage. Genetic factors account for between 7 - 20% of cases of subarachnoid hemorrhage. Ruptured aneurysms that occur in such patients tend to happen at an earlier age, are usually smaller, and are more apt to recur than in those without an inherited condition. A study of people who had suffered subarachnoid hemorrhages found that first-degree relatives of these stroke victims had a high lifetime risk of between 2 - 5%. Some experts recommend screening for aneurysms in people with more than one close relative who suffered a hemorrhagic stroke.

Inherited Disorders that Contribute to Stroke. Some cases of atrial fibrillation may be inherited. Genetic disorders that cause connective tissue disorders are also associated with stroke from hemorrhage; they include polycystic kidney disease, Ehlers-Danlos syndrome type IV, neurofibromatosis type 1, Marfan's syndrome, and moyamoya disease.

Specific Genetic Factors Under Investigation. Specific genetic factors are under investigation. They include:

Inherited deficiencies in protein factors C and S, which inhibit blood clotting, may be responsible for certain cases of stroke in young adults.
A genetic mutation in a factor V Leiden may be related to blood clotting risks.
People who have inherited a gene called apolipoprotein (Apo) E-4 may be at increased risk of stroke. This gene is also associated with Alzheimer's disease.

Stress. One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure, which in turn can increase the risk for stroke.

Depression. Depression has also been linked to higher risk for stroke and lower stroke survival rates. In one study, patients with severe depression had a 73% higher risk for stroke, and those with moderate depression had a 25% higher risk than average. The risk for stroke in African-Americans with depression was 160% higher than average.

Studies indicate that migraine or severe headache may be a risk factor for stroke in both men and women, especially before age 50. Overall, between 2 - 3% of ischemic strokes occur in people with a history of migraine. However, in patients under age 45, about 15% of all strokes (and 30 - 60% of strokes in young women) are associated with a history of migraines, particularly migraine with aura. Some evidence suggests that some strokes in these cases may be due to excessive activation of the nervous system and the dehydration from vomiting that occurs during a severe migraine with aura.

The actual risk itself for migraineurs is low, however. In one study, women with migraines had a 2.7% risk of stroke, with the greatest risk between the ages of 45 - 65. Studies suggest specific risk factors for younger women with migraines, particularly those with auras, include taking high-estrogen oral contraceptives (OCs). (Whether progesterone-alone contraceptives carry any risk is unknown.) In migraineurs who take OCs, the risk increases with high blood pressure, smoking, or both.

Inflammation that occurs with various infections has been associated with stroke. One study found that patients hospitalized for stroke were three times more likely than patients without strokes to have recently been exposed to infections, usually mild ones in the respiratory tract.

Varicella Virus. Varicella zoster virus (the virus that causes chicken pox and shingles) has been associated with cerebral vasculitis, a condition in which blood vessels in the brain become inflamed. It is a very rare cause of stroke in children. The virus has also been associated with some cases of stroke in young adults.

Chlamydia Pneumonia. Some investigators suspect that some infections may produce inflammation in the arteries that can lead to stroke over time. (Similar work is underway in heart disease.) Researchers are particularly interested in Chlamydia pneumoniae, a non-bacterial organism that causes mild pneumonia in adults. Chronic infection has been linked with a higher risk for stroke, and evidence of the organism has been observed in thickened inner vessel walls of the carotid arteries in some studies. Chlamydia has also been linked to heart disease.

Periodontal Disease. A number of studies now strongly support an association between periodontal disease and cardiovascular disorders. According to a major analysis, periodontal (gum) disease is associated with a 20% higher risk for ischemic stroke and heart disease. The added risk may be even greater in adults under 65. Recent evidence points to the inflammatory response as the common element.

Peripheral artery disease (PAD) occurs when atherosclerosis affects the extremities, particularly the feet and legs. The major risk factors for heart disease and stroke are also the most important risk factors for PAD. The occurrence of such conditions in combination with PAD often signals more severe forms of heart or circulatory disease.

In 2007, the American Heart Association (AHA) issued a scientific statement encouraging doctors to change the way they prescribe pain relief medication for patients at risk for heart disease or stroke. The AHA recommends that at-risk patients first try non-drug methods of pain relief (physical therapy, exercise, weight loss to reduce stress on joints, and heat or cold therapy). If these methods don’t work, patients should take the lowest possible dose of acetaminophen (Tylenol) or aspirin. COX-2 inhibitors, such as celecoxib (Celebrex), should be the last resort.

In 2005, the FDA warned that all NSAIDs -- with the exception of aspirin -- carry heart risks. In particular, the NSAIDs ibuprofen (Advil, Motrin) and diclofenac (Cataflam, Voltaren) appear to carry increased risks for heart attack and stroke.

A number of medical or physical conditions may contribute to the risk for stroke:

Sleep apnea. This common disorder, in which the throat becomes obstructed during sleep, may contribute to the narrowing of the carotid artery, appearing to increase the risk for stroke three- to six-fold.
Pregnancy. Pregnancy carries a very small risk for stroke, mostly in women with pregnancy related high blood pressure and in those with cesarean delivery. The risk appears to be higher in the postpartum (post-delivery) period, perhaps because of the sudden change in circulation and hormone levels.
Anti-phospholipid antibodies. Nearly 40% of young people with strokes and 10% of all stroke patients have components of the immune system known as anti-phospholipid antibodies that increase the chance for blood clots.
Sickle-cell anemia. People with sickle-cell anemia are at risk for stroke at a young age.
Drug abuse, particularly with cocaine and, increasingly, methamphetamine, is a major factor in the incidence of stroke in young adults. Anabolic steroids, used for body-building and sports enhancement, also increase risk.

Timing. Like heart attack and sudden cardiac death, stroke appears to be more common in the morning hours, perhaps due to a temporary rise in blood pressure at that time. Various studies point to a higher risk for stroke on weekends, Mondays, and holidays. The risk for hemorrhagic stroke may also be higher in the winter, particularly in older people with high blood pressure.

Homocysteine and Vitamin B Deficiencies. Abnormally high blood levels of the amino acid homocysteine, which occur with deficiencies of vitamin B6, B12, and folic acid, may be linked to an increased risk of coronary artery disease and stroke.

Neck Manipulation. Some studies have reported a higher risk for stroke from injury to the carotid artery after neck manipulation by a chiropractor.

Prognosis

A stroke, the third leading cause of death in the U.S., is always serious. In 2004, over 150,000 Americans died of stroke with women accounting for 61% of these stroke deaths. The mortality rates are declining, however. Over 75% of patients survive a first stroke during the first year, and over half survive beyond 5 years.

People who suffer ischemic strokes have a much better chance for survival than those who experience hemorrhagic strokes. Among the ischemic stroke categories, the greatest dangers are posed by embolic strokes, followed by thrombotic and lacunar strokes. Hemorrhagic stroke not only destroys brain cells but also poses other complications, including increased pressure on the brain or spasms in the blood vessels, both of which can be very dangerous. Studies suggest, however, that survivors of hemorrhagic stroke have a greater chance for recovering function than those who suffer ischemic stroke.

Between 50 - 70% of people recover functional independence after a stroke. However, between 15 - 30% of those who survive either an ischemic or hemorrhage stroke suffer some permanent disability. On the encouraging side, one study reported that people who survived for many years after a stroke had a chance for independent living that was about the same as for their peers who had not suffered strokes. The stroke patients even appeared to be less depressed than the comparison group.

The National Institutes of Health (NIH) have devised a scoring system that helps predict the severity and outcome of the stroke by scoring 11 factors (levels of consciousness, gaze, visual fields, facial movement, motor functions in the arm and leg, coordination, sensory loss, problems with language, inability to articulate, and attention). Up to 70% of patients with ischemic strokes who score less than 10 have a favorable outlook after a year, while only 4 - 16% of patients do well if their score is more than 20.

The risk for recurring stroke is highest within the first few weeks and months. The risk is about 14% in the first year and about 5% thereafter, so preventive measures should be instituted as soon as possible. Some specific risk factors for early recurrence include:

Older age
Evidence of blocked arteries (a history of coronary artery disease, peripheral artery disease, ischemic stroke, or TIA)
Hemorrhagic or embolic stroke
Diabetes
Alcoholism
Valvular heart disease
Atrial fibrillation

Prevention

Forty percent of patients who have had a stroke or TIA will suffer a subsequent stroke within 5 years. In 2006, the American Heart Association/American Stroke Association released guidelines for preventing a second stroke. These guidelines recommend:

Quit Smoking. Also avoid exposure to second-hand smoke.

Maintain Weight. People should aim for a BMI index of 18.5 - 24.9. In people who are obese, reducing weight to this level can reduce the risk for stroke by 15% in men and 22% in women. Waist measurements should be no more than 35 inches for women and 40 inches for men.

Exercise. Everyone in normal health should engage in at least moderate physical activity for a minimum of 30 minutes on most -- if not all -- days of the week.

Limit alcohol. No more than 2 drinks a day for men and 1 drink a day for nonpregnant women.

Healthy Diet. Everyone should aim for a diet that contains a healthy balance of fruits, vegetables, grains, fish, nuts, legumes, poultry, lean meat, and low-fat dairy items. Avoid saturated fats and trans fatty acids.

Improve Cholesterol. People with at least two risk factors and a 10-year risk for heart disease or stroke of more than 20% should aim for LDL levels of less than 100 mg/dl. Raising HDL levels is important for people at risk for stroke. Statins are now used in most cases.

Keep Blood Pressure Low. People in normal health should aim for 139/89 mm Hg or less. Patients with certain health problems, such as diabetes, should aim lower.

Control Diabetes. People with diabetes should aim for fasting blood glucose levels of less than 110 mg/dl and hemoglobin A1C of less than 7%. Blood pressure goals should be 130/80 mm Hg or less.

Take Aspirin or Other Antiplatelet Therapy. People at high risk for heart disease should take a low-dose aspirin every day, unless they have medical reasons to avoid aspirin. (As an alternative to aspirin alone, your doctor may prescribe clopidogrel alone or aspirin plus extended release dipyridamole.) Aspirin may help to prevent strokes caused by blockage in the artery (ischemic stroke), but it may slightly increase the risk of strokes caused by bleeding in the brain (hemorrhagic stroke). The American Heart Association recommends aspirin therapy for women over age 65 who are at risk for stroke.

Control Atrial Fibrillation. People with atrial fibrillation should use anticoagulants to reduce their risk of blood clots. Carotid Endarterectomy Surgery or Stenting: Recommended for most symptomatic patients with neck artery stenosis (narrowing or blockage) of more than 70% and some patients with stenosis of 50 - 69%.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for both ischemic and hemorrhagic stroke. For diet plans, the Mediterranean diet may be a particularly good choice for reducing the risk of stroke. [See In-Depth Report #43: Heart-healthy diet.]

Fruits and Vegetables. Studies suggest that people can protect their heart and circulation by eating plenty of fruits and vegetables. Eating at least five servings a day reduces blood pressure and protects against both heart attack and stroke. Important foods include most fruits (especially potassium-rich fruits including bananas, oranges, prunes, and cantaloupes) and vegetables (especially carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, broccoli). Vegetables, such as broccoli and kale, may be specifically protective against a first ischemic and possibly hemorrhagic stroke. Foods such as apples and tea, which are high in food chemicals called flavonoids, may also be very beneficial.

Whole Grains and Nuts. A 2000 study reported a lower incidence in stroke in women who had a high intake of whole-grain foods. Nuts may also be protective.

Calcium, Potassium, and Magnesium. Calcium, magnesium, and potassium serve as electrolytes in the body. They are important in controlling blood pressure and may also have protective effects against stroke:

Some evidence suggests that diets rich in potassium may protect against stroke by 22 - 40%, mostly by reducing blood pressure but also possibly because of other mechanisms. Low potassium levels may increase the risk for stroke in certain people.

A major study reported that calcium intake is associated with a lower risk for stroke in women, which supports an earlier study reporting a lower risk for stroke in men who drank more milk.

Magnesium deficiencies may increase the risk for atrial fibrillation. No evidence yet exists, however, that taking magnesium supplements is protective.

Salt Restriction. Although the effects of salt restriction are not entirely clear, a 2002 study indicated that even a modest reduction in salt intake for more than a month might reduce the risk of death from stroke by 14% in people with high blood pressure and 6% in people with normal blood pressure.

Fats and Oils. The effects of fats and oils on stroke are complex. One study indicated that middle-aged men without heart disease who had the highest intake of monounsaturated or saturated fat (but not polyunsaturated oils) also had the lowest risk for stroke. Monounsaturated oils, obtained in olive and canola oils, may have protective benefits against both heart disease and stroke. Saturated fats, found in animal products, are known risk factors for heart disease. Some studies suggest, however, that low intake of animal protein and saturated fat increases the risk of hemorrhagic stroke.

Other fat compounds that may be stroke protective are omega-3 fatty acids:

Alpha-linolenic acid is found in canola oil, soybeans, and walnuts. One particular benefit against stroke is its ability to help prevent the formation of blood clots.
Omega-3 fatty acids are categorized as docosahexaenoic (DHA) or eicosapentaneoic acids (EPA). They are found in oily fish and nutritional supplements. These compounds have anti-inflammatory and anti-blood clotting effects and may be significantly beneficial to the heart and reduce the risk for stroke. However, people who have implantable defibrillators should not take fish oil supplements because they may worsen heart rhythm problems.

In any case, consuming fish two or three times a week helps the heart.

Folic Acid and B Vitamins. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid and B6 and B12 vitamins and those who received placebo. And, the vitamins seemed to increase risks for patients who had undergone stenting. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Antioxidant Vitamins. The effects of antioxidant vitamins and carotenoids on stroke have been studied extensively. Most studies have found that these vitamins do not help protect against stroke. An important 2001 study reported no protection from stroke with vitamins A or E or beta carotene. A 2005 study in the Journal of the American Medical Association found that vitamin E definitely does not protect women from stroke or heart attack.

Smoking. Everyone should quit smoking.

Alcohol. Mild-to-moderate alcohol use (one to seven drinks a week) is associated with a significantly lower risk for ischemic stroke, although not hemorrhagic stroke. Heavy alcohol use, particularly a recent history of drinking, is associated with a higher risk of both ischemic and hemorrhagic stroke.

Coffee. In healthy people with normal blood pressure, drinking a couple of cups of coffee a day is unlikely to do any harm. Caffeine may actually have nerve-protecting properties that may help stroke survivors. Caffeine drinkers, however, might do better to choose tea, which may have beneficial nutrients, and people with existing hypertension should avoid caffeine altogether (since caffeine may increase the risk for stroke in this group).

Exercise helps reduce the risk of atherosclerosis, which can help reduce the risk of stroke. Experts recommend at least 30 minutes of exercise on most, if not all, days of the week.

Hypertension is a disorder characterized by chronically high blood pressure. It must be monitored, treated, and controlled by medication, lifestyle changes, or a combination of both.

Reducing blood pressure is essential in stroke prevention. Lifestyle measures such as exercise, weight loss, and healthy diets are important for everyone. Drug therapy is recommended for people with hypertension who cannot control their blood pressure through lifestyle changes. Many different types of drugs are used to control blood pressure. They include ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers, and diuretics. Some drugs, such as Hyzaar, combine an angiotensin receptor blocker with a diuretic to both treat high blood pressure and prevent stroke. [See In-Depth Report #14: High blood pressure.]

In 2004, the National Cholesterol Education Program issued updated recommendations on how to control cholesterol levels. These guidelines emphasize that patients should lower their LDL (“bad”) cholesterol and recommend that more people take LDL-lowering medication. Lowering LDL cholesterol and raising HDL (“good”) cholesterol can significantly reduce the risks of heart disease, including stroke.

Statins have become the most important LDL-lowering drugs. Brands include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). Research increasingly suggests that lowering LDL levels as much as possible is critical for preventing stroke and other heart disease problems. A major analysis of over 200 studies found that statins reduced the risk for heart problems by 60% and stroke by 17%. Another study of over 20,000 people with cerebrovascular disease found that patients who took statin therapy for 2 years reduced their risk of ischemic stroke by 25%.

Statins are proven to reduce the risk of stroke in people at increased risk for heart disease. Research suggests that they may also prevent stroke in patients without heart disease. However, current guidelines recommend that statins should be prescribed to patients without heart disease and with normal LDL levels only if diabetes and several heart disease risk factors are also present.

Researchers are also investigating whether statins might be beneficial in preventing a second stroke in patients who have suffered a stroke or transient ischemic attack (TIA). A study published in 2006 in the New England Journal of Medicine indicated that high-dose atorvastatin (Lipitor) therapy may help reduce the risk of stroke recurrence and other heart events for patients who have had a prior stroke or TIA. In 2006, the FDA expanded atorvastatin’s indications to include reducing the risk of fatal and non-fatal strokes in patients with heart disease

[See In-Depth Report #23: Cholesterol.]

Influenza vaccinations may protect patients with a history of heart attack or heart events. A 2002 study further suggested that flu shots might protect against stroke, although possibly not in patients older than age 75.

Treatment for atrial fibrillation always includes drugs (aspirin or warfarin) to prevent clots from forming. In addition to anticoagulants (blood thinners), other approaches may include:

Restoring or maintaining normal heart rhythm. This is accomplished with anti-arrhythmic drug, cardioversion procedures, or surgery to remove the defective area.
Controlling heart rate. Specific drugs are used for this approach.

Important studies report that controlling heart rate may be the preferable approach. In several studies, rhythm control offered no survival advantages and did not protect against ischemic stroke. Therapies aimed at controlling heart rate, furthermore, had fewer complications.

Drugs to Prevent Blood Clots

After a diagnosis of atrial fibrillation, warfarin (an anticoagulant) or aspirin (an antiplatelet) are essential to prevent blood clots. These drugs can reduce the risk for stroke by over 60% in patients with atrial fibrillation.

Warfarin (Coumadin) is the main anticoagulant (“blood thinner”) drug used to prevent strokes in high-risk patients with atrial fibrillation. Warfarin carries a risk for bleeding, but for most patients, warfarin’s benefits far outweigh its risks. The risk for bleeding is highest when warfarin therapy is first started, with higher doses, and with long periods of treatment. Patients at risk for bleeding are usually older and have a history of stomach bleeding and high blood pressure. It is important that patients who take warfarin have their blood checked regularly to make sure that it does not become “too thin.” Blood that is too thin increases the risk for bleeding, while blood that is “too thick” increases the risk for blood clots and stroke. Prothrombin time (PT) and international normalized ratio (INR) tests are used to monitor blood coagulation.
Aspirin is less effective than warfarin, but has a lower risk for bleeding. It is the preferred treatment for younger people with atrial fibrillation and for people who do not have other risk factors for stroke, such as high blood pressure or diabetes. Aspirin is also prescribed for higher risk patients who cannot tolerate anticoagulation therapy.
Researchers are investigating other drugs for preventing stroke and heart problems in patients with atrial fibrillation. These drugs include the antiplatelet medication clopidogrel (Plavix) and the angiotensin receptor blocker irbesartan (Avapro). Recent research indicates that anticoagulants such as warfarin (Coumadin) work better for atrial fibrillation patients than the combination of clopidogrel plus aspirin. Clinical trials are continuing to investigate whether clopidogrel alone is better than aspirin alone.

Restoring and Controlling Heart Rhythm

To initially restore heart rhythm, anti-arrhythmic drugs are usually tried first. If they fail to restore normal rhythm, cardioversion is often effective. (Some experts suggest trying cardioversion first to avoid side effects of the drugs.) Long-term maintenance therapy using anti-arrhythmic drugs may be required.

Electrical Cardioversion. Electrical cardioversion is mild shock therapy and is the current standard treatment used to restore normal heart rhythm. It is conducted as follows:

Anticoagulants (drugs used to prevent blood clotting) should be administered, if possible, at least 3 weeks before the procedure.
During the procedure, the patient must be conscious and, although sedated, can experience some pain from the procedure.

Although the stabilizing effect is usually only temporary, some evidence suggests that a series of cardioversion may succeed in maintaining normal rhythm in young healthy patients without the need for antiarrhythmic medications.

Low-energy implanted cardioverters (Atrioverter, Jewel AF) are being investigated for maintenance. Studies are promising.

Drugs Used for Maintaining Normal Heart Rhythm. For maintaining a stable rhythm, the following drugs may be used. The specific choices typically depend on whether or not the patient has existing heart disease:

For patients with no heart disease, the first choices include sotalol, flecainide, or propafenone, which are often used sequentially. If these fail, then amiodarone or a newer drug dofetilide (Tikosyn) may be tried. Others include ibutilide (Covert) and azimilide. If these drugs are not effective, other drugs tried include quinidine, procainamide, and disopyramide.
In patients with heart disease, amiodarone, dofetilide, or sotalol are commonly used depending on the cause of heart disease.

Amiodarone is more effective than most others and has been thought to be safer than many other similar drugs. Even in low doses, however, there is a high incidence of side effects, including thyroid disorders, neurologic, skin, and eye problems, and abnormally slow heart beats. Many of these drugs carry a small but significant increased risk, however, for a life-threatening arrhythmia called torsades de pointes. People with certain heart conditions should avoid these drugs.

Surgical Procedures for Complex AF. In some difficult cases, surgery may be recommended. The options and candidates depend on other complicating factors. The following are some examples:

AV node ablation involves severing the communication between the atria (the two upper chambers of the heart) and the ventricles (the two lower chambers). A pacemaker is then implanted just under the skin with electrodes leading to the ventricles. This approach is very effective, but it is irreversible and lifelong. Radiofrequency ablation may be an option in some patients.
A more aggressive procedure uses open chest surgery, in which a maze of cuts is made in the atria. As they heal, the scar tissue prevents the heart circuitry from misfiring. This technique controls atrial fibrillation in more than 90% of appropriate candidates. A new procedure is similar but less invasive.

Controlling Heart Rate

Drugs Used to Control Heart Rate. Beta-blockers or calcium channel blockers are used to control heart rate at the onset of atrial fibrillation. Digitalis, an older drug, is not used as often but can be effective in combination with the other drugs.

Diagnosis

Preventing a major stroke in people who experience transient ischemic attacks or small strokes requires determining the source of such attacks. A complete blood count, chest x-ray, and electrocardiogram are usually performed. Discouragingly, a 2001 study reported that over 30% of patients with TIA who called their primary care doctor were neither evaluated nor sent to the hospital within the month after a first event.

Examining the Carotid Artery. The doctor examines the carotid artery to determine if it is severely narrowed. If so, the patient is in danger of a major stroke. (The thickness of the carotid artery is also an important indicator for long-term risks for stroke, as well as heart disease and mortality rates in general.)

The doctor may use a number of approaches to determine the thickness of the artery:

An important clue to a blocked carotid artery is a bruit. This is a whooshing sound caused by blood flow turbulence in the narrowed artery. A doctor may be able to hear a bruit using a stethoscope. Occasionally, even a patient can hear the sound. The presence of a bruit, however, is not necessarily a sign of an impending stroke, nor does the absence of a bruit indicate an unblocked artery.
Carotid ultrasound is a very valuable tool for measuring the width of the artery. At this time, ultrasound is most useful in people between the ages of 40 and 60 years. Severely blocked carotid arteries may distort some measurements, so other tests may be required to confirm the results.
Measuring blood pressure to the eye may also be important in identifying problems in the carotid artery. If blood flow to the eye is reduced, it is likely that the carotid artery is severely narrowed.

Carotid duplex is an ultrasound procedure performed to assess blood flow through the carotid artery to the brain. High-frequency sound waves are directed from a hand-held transducer probe to the area. These waves "echo" off the arterial structures and produce a two-dimensional image on a monitor, which will make obstructions or narrowing of the arteries visible.

Imaging Techniques for TIAs. Several imaging techniques may identify small clots or other indicators of risk in the brain.

Identifying a Stroke Quickly. To save a patient's life, a fast diagnosis of both the presence and type of stroke is critical. Health professionals have devised different tests to help emergency workers quickly identify a person with stroke even before they reach the hospital. For example, an assessment tool called Face, Arms, Speech, Time (FAST) is highly accurate. It involves watching for the following signs:

(F)ACE. Ask the person to smile. Check to see if one side of the face droops.
(A)RMS. Ask the person to raise both arms. See if one arm drifts downward.
(S)PEECH. Ask the person to repeat a simple sentence. Check to see if words are slurred and if the sentence is repeated correctly.
(T)IME. If a person shows any of these symptoms, time is essential. It is important to get to the hospital as quickly as possible. Call 9-1-1. Act FAST.

Determining Ischemia Versus Hemorrhagic Stroke. Once a stroke has been identified, the next important step is to determine as quickly as possible whether it is hemorrhagic or ischemic. Clot-busting drug therapies can be life-saving for ischemic stroke patients, but they are effective only in the first 3 hours. In addition, they cause bleeding and can be lethal if the stroke is caused by a hemorrhage.

A computed tomography (CT) scan is essential for identifying or ruling out hemorrhagic strokes. The goal is to complete the CT examination and obtain and interpret the results within 45 minutes of arrival at the hospital. (An ultrasound technique called transcranial duplex sonography may be sensitive enough to differentiate between hemorrhagic and ischemic strokes if CT scans are not available.)

Certain factors suggest a hemorrhagic rather than ischemic stroke. They include specific symptoms (coma, vomiting, and severe headache), taking anticoagulants, very high systolic blood pressure, or high blood sugar levels in nondiabetics. However, such findings are not conclusive, and a CT scan or MRI is always needed.

Ruling Out Other Disorders. In most cases of stroke, the diagnosis is evident although a number of conditions may cause similar symptoms. These include seizures, infections that cause mental confusion, syncope (fainting), hypoglycemia, and brain tumors.

Magnetic Resonance Imaging (MRI). MRI uses a magnetic field to provide 3-dimensional images of the brain. In 2007, an important Lancet study of emergency room patients clearly indicated that MRI is superior to computed tomography (CT) in assessing whether a stroke has occurred. The MRI appears to work especially well for detecting ischemic stroke (stroke caused by blood clot). In the study, MRI accurately detected presence or absence of acute stroke in 80% of patients compared to 58% for CT. (Acute stroke included both ischemic and hemorrhagic types.) MRI detected acute ischemic stroke in 40% of patients compared to 10% for CT. In addition, MRI detected ischemic stroke within 3 hours of symptom onset (an important timeframe for delivering clotbuster drugs) in 46% of patients compared to only 7% for CT. Both MRI and CT performed similarly for detecting hemorrhagic stroke.

Computed Tomography. A computed tomography (CT) test uses x-ray images to take pictures of the skull and brain. Sometimes a dye is injected into a patient’s veins to enhance image contrast. Although research indicates that MRI is better in determining ischemic stroke, CT still may be useful in diagnosing hemorrhagic strokes.

Ultrasound. Ultrasound may be used in different circumstances. This imaging technique is painless and noninvasive.

Carotid ultrasound (also called Doppler or duplex sonography) can determine blockage in the carotid arteries that could lead to or be causing a stroke.
Transcranial duplex sonography can identify blockage in large arteries in stroke patients and to monitor the effects of thrombolytic therapy.

Cerebral Angiography. Cerebral angiography is an invasive procedure that may be used for patients with TIAs who require surgery. It can also detect aneurysms and monitor thrombolytic therapy. It requires the insertion of a catheter into the groin, which is then threaded up through the arteries to the base of the carotid artery. At this point a dye is injected, and x-rays, CTs, or MRI scans determine the location and extent of the narrowing, or stenosis, of the artery. In people with TIAs the risk of stroke itself increases using this technique, particularly in elderly people with diabetes.

Other Techniques. Other imaging tests, including positron-emission tomography (PET) and single photon-emission computed tomography (SPECT), may also help the doctor identify injuries caused by the stroke.

Electrocardiogram (ECG). A heart evaluation using an electrocardiogram (ECG) is important in any patient with a stroke or suspected stroke. An ECG records the electrical current in the heart muscle.

Echocardiogram. An echocardiogram uses ultrasound to view the chambers and valves of the heart. It is generally useful for stroke patients to identify blood clots or risk factors for blood clots that can travel to the brain and cause stroke. There two are types:

Transthoracic echocardiograms (TTE) view the heart through the chest. It is noninvasive and is the standard approach.
Transesophageal echocardiogram (TEE) examines the heart using an ultrasound tube that the patient literally swallows and passes down the throat. It is uncomfortable and requires sedation. It is typically used to obtain more accurate images of the heart if a TTE has suggested abnormalities, such as atrial fibrillation or patent foramen ovale (PFO).

Patients who have a TIA are at increased risk for a major stroke in the days and weeks that follow. The ABCD² score is a tool that helps doctors predict short-term stroke risk following a TIA. The ABCD² score assigns points for various factors:

Age (over 60 years)
Blood pressure (greater or equal to 140/90 mm Hg)
Clinical features (weakness on one side of the body; speech impairment without weakness
Duration of TIA symptoms (at least 60 minutes)
Diabetes

Based on the number of points, a doctor can identify whether a patient is at low, moderate, or high risk of having a subsequent stroke within 2 days after a TIA. Several 2006 and 2007 studies indicated that the ABCD² score works well in predicting stroke, and can help doctors better decide which patients require hospitalization and emergency care.

Blood Tests. Several blood tests may help predict the risk for a stroke and determine the severity and complications of an existing stroke.

Specific blood tests are important to determine clotting times, to check electrolytes (potassium, calcium, sodium), and to measure factors indicating liver or kidney problems. Kidney tests measure blood proteins that are filtered through the kidneys. These proteins include creatinine and blood urea nitrogen (BUN). A more recent type of kidney test measures the protein cystatin C. Recent research suggests that the cystatin C kidney test may be better at predicting cardiovascular risks in elderly patients.
Blood sugar (glucose) levels are measured. Hyperglycemia (high levels) may indicate a worse outcome for some strokes (although not hemorrhagic or lacunar strokes). Hypoglycemia (low levels) is a common complication of diabetes treatments, and its symptoms may mimic those of a stroke.
A new blood test, the PLAC test, was approved in 2005 to help diagnose people at increased risk for ischemic stroke. The PLAC test measures an enzyme called lipoprotein-associated phospholipase A2 (Lp-PLA2). Patients with high levels of this protein have twice the risk for ischemic stroke as patients with normal levels.

Examination of Spinal Fluid. If the CT scan is negative but the doctor still suspects a subarachnoid hemorrhagic stroke, a spinal tap may be performed. Spinal fluid containing significant amounts of blood will usually confirm a hemorrhagic stroke.

Managing a Stroke

Until recently, the treatment of stroke was restricted to basic life support at the time of the stroke and rehabilitation later. Now, however, treatments can be dramatically beneficial when administered as soon as possible after the onset of the stroke. It is critical to get to the hospital and be diagnosed as soon as possible. There are several steps in the initial assessment and management of a person with a stroke.

If significant symptoms appear in people at risk for stroke, calling 911 is critical (as opposed to calling the family doctor or trying to get the patient to the hospital by car). One study reported that patients who went to the emergency room in an ambulance had a much shorter delay in getting treatment than those who went on their own. Receiving treatment early is critical in reducing the damage from a stroke.

Important diagnostic and evaluation steps are needed for the optimal treatment of a stroke patient:

Determine Whether the Stroke Is Ischemic or Hemorrhagic. As soon as the patient enters the hospital, diagnostic tests, particularly a CT scan, should occur to determine whether the stroke is ischemic or hemorrhagic.

Determine The Need for Thrombolytic Drugs. If the stroke is ischemic, the next step is to determine if the patient would benefit from blood clot-busting drugs (called thrombolytics). The following factors can assist in making this decision:

Estimate the time of onset of the stroke. Time is critical in the decision-making process. Clot-buster drugs do not generally help if given more than 3 hours after stroke onset. Onset is when the patient first experiences any symptoms, even minor impairment. If the patient had a previous TIA that completely resolved before the stroke, however, onset is dated from when the more recent symptoms developed.
Tell the doctor if the patient has been taking any blood-thinning drugs.
Give the doctor a thorough history of any accompanying medical or physical condition and any recent event, such as surgery or injury, which might contribute to the condition.
CT scans will indicate if there are extensive early injuries, which might affect the decision to use these drugs.

The patient should receive treatment to support basic life functions and to reduce stress, pain, and agitation. The following steps are also very important:

Maintain Adequate Delivery of Oxygen. It is very important to maintain oxygen levels. In some cases, airway ventilation may be required. Supplemental oxygen may also be necessary for patients when tests suggest low blood levels of oxygen. Hyperbaric oxygen (which is oxygen administered under pressure) may help specific stroke patients, although it is not recommended for most patients, since there is some risk of significant adverse effects using this approach.

Managing Fever and Lowering Body Temperature (Hypothermia). Fever should be aggressively treated, since strong evidence suggests that its presence predicts a poorer outlook. Some evidence suggests that hypothermia -- reducing body temperature -- might protect nerve cells in stroke patients. Cooling is done through special cooling blankets, ventilators, or infusion of cool fluids. Unfortunately, severe side effects occur with even moderate hypothermia (86°F, 30°C), which can include pneumonia, blood clotting disorders, heart rhythm disturbances, and others.

Maintain Electrolytes. Maintaining a healthy electrolyte balance (the ratio of sodium, calcium, and potassium in the body's fluids) is critical.

Managing Blood Pressure. Managing blood pressure is essential and complicated. Patients with stroke and pressures above 220 (systolic) or 120 (diastolic) should be treated. Lowering blood pressure too quickly can be dangerous, however, in patients with both ischemic and hemorrhagic strokes. In general, experts do not advise aggressively lowering elevated pressures below 220/120 mm Hg in patients unless they have other conditions, such as a heart attack, that require pressure-lowering treatments. In patients who require thrombolytic drugs, blood pressure should cautiously be lowered to 185/110 mm Hg. In most cases, blood pressure declines when these patients become stabilized.

Managing Increased Brain Pressure. Hospital staff should watch carefully for increased pressure on the brain, which is a frequent complication of hemorrhagic strokes. It can also occur a few days after ischemic strokes. Early symptoms of increased brain pressure are drowsiness, confusion, lethargy, weakness, and headache. Medications such as mannitol may be given during a stroke to reduce pressure or the risk for it.

Keeping the top of the body higher than the lower part, such as by elevating the head of the bed, can reduce pressure in the brain and is standard practice for patients with ischemic stroke. However, this practice also lowers blood pressure in general, which may be dangerous for patients with massive stroke.

Monitoring the Heart. Heart attack and arrhythmias are potential complications of ischemic stroke. Patients must be monitored using electrocardiographic tracings.

Controlling Glucose Levels. Elevated blood sugar (glucose) levels can occur with severe stroke and may be a marker of serious trouble. In general, it is advisable to lower glucose levels that are about 300 mg/dL, usually with insulin. It is not clear, however, if glucose-lowering treatments offer any advantage. Excessive lowering of glucose levels can have damaging effects on the brain. Studies are underway to determine the best approach.

Medications

Intravenous Thrombolytics. Clot-busting (thrombolytic) drugs break up existing blood clots. They are among the important treatments for heart attacks, and are now also used for ischemic (not hemorrhagic) stroke. While research has confirmed that early treatment with thrombolytics can greatly increase a stroke patient's chances for recovery, their use has been limited due to the short treatment window (within 3 hours of onset of stroke symptoms). The standard thrombolytic drugs are tissue plasminogen activators (t-PAs). They include alteplase (Activase) and reteplase (Retavase).

The following steps are critical before administering these clot-buster drugs:

Before the thrombolytic is given, a CT scan must first confirm that the stroke is not hemorrhagic. If the stroke is ischemic, a CT scan can also suggest if injuries are very extensive, which might affect the use of thrombolytics.
Thrombolytics must be administered within 3 hours of a stroke to have any effect. According to a 2004 review of clinical trials, best results are achieved if patients are treated with 90 minutes of a stroke. Unfortunately, most stroke patients arrive at the hospital more than 3 hours after an attack and therefore are not eligible for treatment. There is some evidence that t-PA administered with 4 hours may also be effective, but more research needs to be conducted. These findings underscore the critical need for people to go to a hospital immediately if a stroke is suspected.

Thrombolytics carry a risk for hemorrhage, so they may not be appropriate for patients with existing risk factors for bleeding. They should not be used in patients who are experiencing seizures. The drug may be appropriate in more patients than previously thought, however, including older people, those with a history of stroke, and those with high blood pressure. Although older studies cited concern over the safety and effectiveness of t-PA, a 2004 review of clinical trial data found that patients who received t-PA were two times more likely to experience a favorable outcome than those who did not receive this treatment.

Intra-Arterial Thrombolytics. Researchers are investigating thrombolytics injected directly into an artery in the brain. Early studies suggest this approach may allow effective treatment up to 6 hours after a stroke and improve recovery in more patients. The risk for bleeding and hemorrhagic stroke is significantly increased, however.

Fibrin-Depleting Drugs. These drugs deplete the amount of fibrinogen in blood, which in turn reduces the "stickiness" in blood. Such drugs include ancrod and batroxobin (Defibrase), both derived from the venom of poisonous snakes. Some experts believe these drugs might be a possible alternative to thrombolytics. Studies suggest they may modestly reduce the risks for death and disability if given early on. As with all anti-clotting drugs, there is a higher risk for hemorrhage, but it appears to be slight.

Medications that prevent blood from clotting are used to prevent a recurring or second stroke. Anticlotting drugs include antiplatelets and anticoagulants.

Antiplatelet Drugs.Blood platelets are involved in blood clotting. Antiplatelets prevent clotting by blocking the accumulation of platelets. An antiplatelet drug -- most often aspirin -- is given within 48 hours of an ischemic stroke and continued in low doses as maintenance therapy. Studies suggest that antiplatelet therapy can reduce the risk for a second stroke by 25%.

Aspirin. Aspirin is recommended within 48 hours of a first ischemic stroke in doses of 50 - 325 mg. Daily low-dose aspirin may also help prevent a second ischemic stroke. Experts also recommend aspirin combined with the antiplatelet drug dipyridamole (Aggrenox). A 2006 study indicated that aspirin plus dipyridamole may be better than aspirin alone in preventing a heart attack or major stroke in patients who have had a minor ischemic stroke. Patients should not be given an aspirin until a diagnosis of ischemic or hemorrhagic stroke has been determined. Aspirin increases the risk for bleeding in patients with hemorrhagic stroke and can be dangerous.
Thienopyridines. Clopidogrel (Plavix) and ticlopidine (Ticlid) are antiplatelet drugs known as thienopyridines. (Clopidogrel is preferred over ticlopidine because of its better safety record.) Evidence suggests that clopidogrel plus aspirin is better than aspirin alone in reducing blood clots in patients who have carotid artery blockage (carotid stenosis). Other studies indicate that clopidogrel alone may be sufficient for patients who have had a recent ischemic stroke or TIA. A study of over 7,000 of these patients found that adding aspirin to clopidogrel therapy provided no additional benefit and increased the risk of bleeding; therefore, aspirin plus clopidogrel is not usually recommended for most patients who have had an ischemic stroke or TIA. Clopidogrel alone may also be better than aspirin alone in preventing a third stroke or heart attack in high-risk patients.
Glycoprotein IIB/IIIa Inhibitors. Glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors are sometimes administered intravenously in the hospital and include abciximab (ReoPro, Centocor), eptifibatide (Integrilin), tirofiban (Aggrastat), lotrafiban, and lamifiban. They are being investigated alone or as additions to thrombolytic (clot-busting) drugs.

Anticoagulants.Anticoagulants thin blood and may be useful under certain circumstances.

Warfarin. The anticoagulant warfarin (Coumadin) may not work as well as aspirin in preventing a second stroke in people who have partial artery blockage in the brain (intracranial stenosis). Warfarin is, however, very important in high-risk patients with atrial fibrillation. It may be useful in other situations, such as patients with patent foramen ovale (PFO), those whose stroke followed a heart attack, or in high-risk patients who cannot take antiplatelet drugs.
Heparin. Intravenous heparin, a potent anti-platelet drug, has been used for ischemic stroke since 1941. Although many doctors continue to use it, five out of six major studies have reported no clear protective benefits compared to aspirin with the use of standard heparin or any heparin-like drugs. They also pose a much higher risk for hemorrhagic stroke. Experts now recommend heparins only for preventing thromboembolism in stroke patients at risk for this condition.
Direct Thrombin Inhibitors (DTIs). Direct thrombin inhibitors are a more recent group of anti-coagulants. The first DTI is hirudin, a natural substance derived from the saliva of leeches. New forms include argatroban (Novastan), bivalirudin (Angiomax), danaparoid (Orgaran), lepirudin (Refludan), desirudin (Revasc), inogatran, and efegatran. Ximelagatran (Exanta) is new oral drug that is showing great promise for protection against stroke in patients with atrial fibrillation while posing a low risk for bleeding.

All anti-clotting drugs carry a risk for bleeding and a slightly increased risk for hemorrhagic stroke.

It is important that patients control their high blood pressure and LDL (“bad”) cholesterol levels. Various drugs, such as statins, diuretics, and ACE inhibitors, can manage these conditions. People with diabetes should also maintain tight control of their blood sugar levels.

Calcium Channel Blockers. Early administration of calcium channel blockers, such as nimodipine (Nimotop), can improve functional outcome. One of the most common and serious dangers after a subarachnoid hemorrhagic stroke is spasm of the blood vessels near the ruptured site, which closes off oxygen to the brain. Calcium causes contraction of the smooth muscles of the blood vessels; calcium channel blockers are drugs that relax the blood vessels. The drugs work best if they are administered within 6 hours of the stroke. Calcium channel blockers are not useful for ischemic strokes, although they can be used in combinations with blood pressure lowering drugs to prevent them.

Nerve-Protecting Drugs. More than 50 medications have been studied in clinical trials aimed at slowing or preventing the cascading process that destroys nerve cells after a stroke. Many investigative drugs are targeting the excitatory amino acids, such as glycine and glutamate, which are known to destroy nerve cells after a stroke. Although none to date have proven to have any significant benefits, some are showing promise. They include magnesium sulfate, citicoline, ebselen, piracetam, edaravone, albumin, erythropoietin, and NXY-059.

Investigative Drugs for Nerve Regeneration. Scientists used to think that when cells in the brain were destroyed, new ones could not grow to replace them. Researchers have now observed, however, that nerve regrowth (neurogenesis) can occur in the adult human brain. This exciting discovery opens the way for new drugs that might in the future stimulate nerve growth and repair damage done by many neurologic diseases, including stroke. For example, a 2002 study reported nerve regeneration in animals whose brains were treated with the drug inosine. More research is underway.

Surgery

Carotid endarterectomy is a surgical procedure that cleans out and opens up the narrowed carotid artery. It is used in patients at high risk for thrombotic ischemic strokes, which are caused by blockages in the internal carotid artery. It is also sometimes used after a stroke. In such cases, patients have reported improvements in vision, speech, swallowing, functioning of arms and legs, and general quality of life.

There is a risk of a heart attack or stroke from the procedure. Anyone undergoing this procedure should be sure their surgeon is experienced in recent techniques and that the medical center has complication rates of less than 6%. A 2000 study reported that older surgeons had a worse record than younger ones, possibly because they relied on residents or were less likely to adopt new procedures.

Procedure Description. The procedure generally is as follows:

The patient is usually given general anesthesia, although it has been reported that using local anesthetic is just as safe and reduces the cost of the procedure.
A bypass tube is put in place to transport blood around the blocked area during the procedure.
The surgeon scrapes away the plaque on the arterial wall.
The artery is sewn back together, and blood flow is restored.
The patient generally stays in the hospital for about 2 days. There is often a slight aching in the neck for about 2 weeks, and the patient should refrain as much as possible from turning the head during this period.

Endarterectomy is a surgical procedure removing plaque material from the lining of an artery.

Click the icon to see an illustrated series detailing surgery for unblocking carotid arteries.

Determining Who Should Have Surgery. Evidence strongly suggests that most patients with severe stenosis (over 70% of the carotid artery is obstructed) can benefit from either carotid endarterectomy or carotid artery stenting. An experienced surgeon with a good track record is essential. Patients with mild stenosis (less than 50% obstruction) should not have endarterectomy; these patients do better with medications even if they have symptoms. For patients with moderate stenosis (50 - 69%), the decision to perform surgery needs to be determined on an individual basis. When a carotid endarterectomy procedure is recommended, it should be performed within 2 weeks.

Carotid angioplasty and stenting (CAS) is being investigated as a less-invasive alternative to carotid endarterectomy. It is based on the same principles as angiography done for heart disease.

An extremely thin catheter tube is inserted into an artery in the groin.
It is threaded through the circulatory system until it reaches the blocked area in the carotid artery.
The doctor either breaks up the clot or inflates a tiny balloon against the blood vessel walls (angioplasty).
After temporarily inflating the balloon, the doctor typically leaves a circular wire mesh (stent) inside the vessel to keep it open.

This procedure carries a risk for an embolic stroke and other complications. At this time, it is being used in some centers as an alternative to endarterectomy in patients who cannot undergo endarterectomy, especially for patients with severe stenosis (blockage greater than 70%) and high surgical risk. Several studies published in 2006 suggested that CAS should be used only for patients with these types of conditions. One of these trials, EVA-3S, was stopped early because results clearly indicated a higher 30-day risk of death and stroke in patients who underwent CAS. Experts are waiting for results of further trials comparing stenting and endarterectomy.

Hemicraniectomy is surgical removal of a bone patch from the skull to relieve pressure. The bone is stored under sterile conditions and reimplanted a few months latter. It may have be a life-saving option for some patients with severe stroke that has resulted in swelling and injury to a large area in the brain. Studies are showing some benefits for high-risk patients, but more information is needed to determine specific conditions that will respond to this treatment.

Extracranial-intracranial (EC-IC) bypass has been under investigation for decades for ischemic stroke, but has had very mixed results, some extremely negative. With this procedure, a healthy artery in the scalp is rerouted to an area of the brain that was deprived of blood because of a blocked artery. This procedure is now sometimes used for patients with aneurysms. Some experts hope, however, that, in specific cases chosen via careful imaging and using the latest surgical techniques, EC-IC may prove to be helpful for some stroke patients.

Surgical Intervention of the Ruptured Aneurysms. In patients with subarachnoid hemorrhagic stroke, surgery to block off the aneurysm is usually recommended within a few days of the stroke. The standard procedure is to clip the aneurysm and stop bleeding. Alternative approaches are promising.

Surgical Intervention of Unruptured Aneurysms. If an unruptured aneurysm is detected, patients should discuss all options with their doctor, including surgical repair. Unruptured aneurysms occur in between 1 - 8% of the general population, however, and controversy exists over when to operate and on which patients.

In general, the decision rests on the size of the aneurysm, but uncertainty still exists. In one study, for example, the risk of rupture for aneurysms between 10 - 25 mm was quite low -- slightly less than 1% per year for both groups. Aneurysms over 25 mm, however, had a 6% chance of rupturing within a year. Studies have reported that in general, the risk for rupture is between .05 - 2% a year, but recent evidence suggests that the risks may be even less. In one study, even people with a history of subarachnoid hemorrhage had only a 0.5% annual risk for recurrence when aneurysms were small.

Aneurysms can often cause symptoms, however, even if they do not rupture. Patients should discuss their particular risk factors carefully with their doctors. Individuals with arteriovenous malformation, a condition caused by abnormal associations between arteries and veins, should be monitored for the development of an aneurysm.

Clipping the Aneurysm. The standard surgical procedure for treating a ruptured aneurysm is to place a clip across the neck of the aneurysm, which blocks off bleeding. It is usually performed within the first 3 days. Getting to the aneurysm is often extremely difficult. Deep cooling of the body to stop circulation may be used to allow more time for the operation. Procedures that remove large portions of the bone in the skull are being developed to allow fast access. There is a relatively high risk for newly formed aneurysms, particularly after 9 years. Patients may want to discuss follow-up angiography to detect any new aneurysms 9 - 10 years after the procedure.

Transcatheter Embolization for Sealing off the Aneurysm. Transcatheter embolization is a new technique for ruptured and unruptured aneurysms that is proving to be effective, although it is still investigational. The surgeon threads a thin tube through the artery leading to the aneurysm through which materials are passed to plug or obstruct the aneurysm. In one version of this procedure, the following occurs:

A tiny platinum coil is inserted through the tube and positioned into the aneurysm.
An electric charge is passed through the coil to form blood clots.
In this case, blood clots benefit the patient by using the coil as a scaffold and sealing off the aneurysm.

A 2002 study suggested it could be attempted safely in over 95% of patients with unruptured aneurysms. In the study, the procedure eliminated the aneurysm in nearly 90% of the patients. In small trials using the coil with a ruptured aneurysm, only 3.7% of patients suffered a second stroke after 7 months compared to the usual re-rupture rate of 30 - 40%.

Emergency Surgery for Hemorrhagic Strokes. Emergency surgery for a hemorrhagic stroke involves locating and removing large blood clots. In the past, such procedures had little effect on survival. Advances, however, are improving outcomes when surgery is performed very early.

Recovery

After a stroke, patients should take all necessary measures, including medications and lifestyle changes, to prevent another stroke. For those whose stroke was ischemic, aspirin, warfarin, or both will usually be prescribed.

Having a neurologist as the primary doctor after a stroke, rather than some other specialist or primary care doctor, significantly increases the chance for survival. Patients or their families should be persistent in requesting the best care possible during this important early period.

Receiving initial treatment at a stroke unit, instead of a general ward, plays a strong role for better long-term quality of life. Rehabilitation services aimed at patients living at home are also very effective in improving independence. Patients or their families should seek patient advocates or support associations to ensure they receive the right care.

In addition to problems brought on by neurologic damage, stroke patients are also at risk for other serious problems that reduce their chances for survival. They include:

Blood clots in the legs (deep vein thrombosis)
Pulmonary embolism (a blood clot that travels to the lungs)
Pneumonia
Widespread infection
Heart problems
Urinary tract infections (a catheter is sometimes used in the first 48 hours after stroke to help with urinary retention, but if it is left in longer it can cause urinary tract infections)

Measures should be taken to monitor and treat patients for these important problems.

In all, 90% of stroke survivors experience varying degrees of improvement after rehabilitation. The current cost-cutting climate generates pressure to send elderly patients who have had a stroke directly to a nursing home rather than a rehabilitation first. Not all patients, however, need or benefit from formal rehabilitation:

If the stroke is severe, intensive training would not be helpful.
If the stroke is mild, patients often improve on their own.

Positive factors that help predict good candidates for rehabilitation:

A patient should be able to sit up for at least an hour.
The patient should be able to learn and be aware.
Spasticity may be a good sign, because it indicates live nerve action.
Patients who are able to move their shoulders or fingers within the first 3 weeks after having a stroke are more likely to recover the use of their hands than patients who cannot perform these movements. The ability to feel light pressure on the affected hand, however, makes no difference for future hand movement.
Family members or close friends are available to be active participants in the rehabilitation process.

Factors that predict a poor response to rehabilitation:

Dysphagia (the inability to swallow) is associated with a higher mortality rate, possibly because of increased risk for infection and malnutrition. Dysphagic patients are given nutrition using a stomach tube or a feeding tube inserted down through the nose.
Incontinence.
The inability to recognize nonspeech sounds that occur right after a stroke.
A poor hand grip that is still present after 3 weeks is an indicator of severe problems.
Having had very severe seizures after the stroke.

Factors that do not rule out rehabilitation:

About 30% of patients experience aphasia (an impaired ability to speak). However, this disability does not necessarily affect the ability to think. Aphasia can also be temporary.
Although confusion is common among people who have had strokes, partial or even complete recovery is very possible.

Physical therapy should be started as soon as the patient is stable, as early as 2 days after the stroke. Some patients will experience the fastest recovery in the first few days, but many will continue to improve for about 6 months or longer. Because stroke affects different parts of the brain, specific approaches to managing rehabilitation vary widely among individual patients:

Exercise program. Recent guidelines from the Veteran’s Administration recommend that patients get back on their feet as soon as possible to prevent deep vein thrombosis. Patients should try to walk at least 50 feet a day. Assisted devices or bracing are sometimes used to help support the legs. Treadmill exercises can be very helpful for patients with mild-to-moderate dysfunction. Exercise should be tailored to the stroke survivor's physical condition and can include aerobic, strength, flexibility, and neuromuscular (coordination and balance) activities.
Retraining muscles. Stretching and range-of-motion exercises are used to help treat spastic muscles. They can also help patients regain function in a paralyzed arm. There are several approaches. The Bilateral Arm Training with Rhythmic Auditory Cueing (BATRAC) technique involves moving a bar with both arms in a sustained rhythmic pattern. A 2004 study in the Journal of the American Medical Association (JAMA) reported that BATRAC helped patients get back use of their paralyzed arm. Patients had a stroke at least 4 years before participating in the BATRAC study. Another technique, constraint-induced movement therapy (CIMT), involves doing a series of repetitive exercises while the less functional arm is restrained. Research published in 2006 in JAMA indicated that 2 weeks of CIMT can help patients regain arm function. Patients in the CIMT study had experienced a stroke within the prior 3 - 9 months.
Speech therapy and sign language. People who have had a stroke often have aphasia, a brain condition that makes it difficult to speak and understand language. Aphasia can come in many different forms. A person may be unable to speak at all, or just have difficulty saying the right word. Intense speech therapy after a stroke is important for recovery. Some experts recommend 9 hours a week of therapy for 3 months. A 2005 study indicated that a shorter period (3 hours a week for 10 days) also works well. Language skills improve the most when family and friends help reinforce the speech therapy lessons.
Biofeedback techniques combined with physical therapy. This combination has been beneficial in certain cases. Electrical stimulation of the throat, for example, may help patients with dysphagia recover their ability to swallow faster. Stimulation of the wrist and finger is also showing promise for improving motor capabilities.
Swallowing exercise. A promising study reported that swallowing improved when patients performed a simple exercise 3 times a day for 6 weeks. They lay flat and raised their heads three times, holding them up for 1 minute with a 1 minute rest in between. This was followed by 30 consecutive head lifts.
Attention training. Problems with attention are very common after strokes. Direct retraining teaches patients to perform specific tasks using repetitive drills in response to certain stimuli. (For example, they are told to press a buzzer each time they hear a specific number.) A variant of this approach trains patients to relearn real-life skills, such as driving, carrying on a conversation, or other daily tasks.
Occupational training. Occupational therapy is important and improves daily living activities and social participation.

Drug therapy can sometimes help relieve specific effects of stroke:

Dantrolene (Dantrium), tizanidine (Zanaflex), and baclofen (Lioresel) are used to treat spasticity.
Heparin, a blood-thinning drug, is used to prevent blood clots from forming in the veins of the legs (thrombosis).
Some patients experience constant hiccups, which can be very serious. Among the drugs used for this condition are chlorpromazine or baclofen.
Studies have reported that dextroamphetamine or methylphenidate (Ritalin), an amphetamine used in attention deficit disorder, may help patients recover speech and motor skills when combined with physical therapy.

Certain drugs commonly taken for conditions associated with stroke may actually slow recovery. They include drugs used for high blood pressure, including clonidine and prazosin, anticonvulsant drugs, the antipsychotic drug haloperidol, and anti-anxiety drugs such as benzodiazepines.

The Emotional State of the Patients. Strong motivation with the goal of independence after rehabilitation is important for recovery. Unfortunately, depression is very common after a stroke, both as a direct and indirect result of the stroke:

Strokes that affect the right hemisphere in the brain increase the risk for depression.
Patients can become depressed by the changes in their ability to function.
A peculiar stroke-induced condition, known as post-stroke crying or neurologic emotionalism, is a neurologic not a psychologic disorder.

If depression is prolonged, it can interfere with recovery. One study showed that people who suffered strokes and became depressed were three times more likely to die within 10 years than stroke victims who were not depressed. There is a significantly increased risk of suicide in patients with stroke, especially in women and those under age 60.

Antidepressants, particularly fluoxetine (Prozac) and similar so-called SSRI drugs, have been beneficial in relieving post-stroke crying as well as improving recovery in general and mood in particular. Antidepressants may also help restore mental abilities.

Some doctors also recommend tricyclic antidepressants, which include amitriptyline (Elavil) and nortriptyline (Pamelor). In one study nortriptyline (Pamelor) not only improved mood but also had positive effects on mental functioning, suggesting perhaps that some dementia associated with stroke may actually be due to depression. Tricyclics may also be useful for neurologic emotionalism.

Anxiety disorder is also common and debilitating. Some research indicates that many patients suffer from feelings identical to post-traumatic stress syndrome. The two disorders often overlap, but drug treatments for each differ and may offset the other.

Many drugs for psychologic disorders affect the central nervous system and can delay rehabilitation. Skilled professional help is needed to determine the most effective and safest treatments.

The Emotional State of the Caregiver. The caregiver's emotions and responses to the patient are critical. Patients do worse when caregivers are depressed, overprotective, or not knowledgeable about the stroke. Unfortunately, in one study, over half of the caregivers themselves were depressed, particularly if the stroke victims were left with dementia or abnormal behavior.

Resources

www.strokeassociation.org -- American Stroke Association
www.americanheart.org -- American Heart Association
www.stroke.org -- National Stroke Association
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aphasia.org -- National Aphasia Association
www.aan.com -- American Academy of Neurology
www.strokecenter.org/trials -- Stroke Trials Directory

References

ACTIVE Writing Group on behalf of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet. 2006 Jun 10;367(9526):1903-12.

Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10;355(6):549-59.

Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007 Mar 27;115(12):1634-42. Epub 2007 Feb 26.

Chalela JA, Kidwell CS, Nentwich LM, Luby M, Butman JA, Demchuk AM, et al. Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet. 2007 Jan 27;369(9558):293-8.

ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006 May 20;367(9523):1665-73.

Johnston SC, Rothwell PM, Nguyen-Huynh MN, Giles MF, Elkins JS, Bernstein AL, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet. 2007 Jan 27;369(9558):283-92.

Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE. Migraine and risk of cardiovascular disease in women. JAMA. 2006 Jul 19;296(3):283-91.

Mas JL, Chatellier G, Beyssen B, Branchereau A, Moulin T, Becquemin JP, et al. Endarterectomy versus stenting in patients with symptomatic severe carotidstenosis. N Engl J Med. 2006 Oct 19;355(16):1660-71.

Mosca L, Banka CL, Benjamin EJ, Berra K, Bushnell C, Dolor RJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007 Mar 20;115(11):1481-501.

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. Heart disease and stroke statistics -- 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28.

SPACE Collaborative Group; Ringleb PA, Allenberg J, Bruckmann H, Eckstein HH, Fraedrich G, et al. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial. Lancet. 2006 Oct 7;368(9543):1239-47.

Thavendiranathan P, Bagai A, Brookhart MA, Choudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.

Tsivgoulis G, Spengos K, Manta P, Karandreas N, Zambelis T, Zakopoulos N, et al. Validation of the ABCD score in identifying individuals at high early risk of stroke after a transient ischemic attack: a hospital-based case series study. Stroke. 2006 Dec;37(12):2892-7. Epub 2006 Oct 19.

Wolf SL, Winstein CJ, Miller JP, Taub E, Uswatte G, Morris D, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9months after stroke: the EXCITE randomized clinical trial. JAMA. 2006 Nov 1;296(17):2095-104.

Review Date:
4/16/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes - type 1

FitSugar — Wed, 08 Oct 2008 17:35:05 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Life-Threatening Complicati...
Diagnosis
Dietary Goals and Exercise...
Treatment
Monitoring Tests
Long-Term Complications
Transplantation Procedures...
Prevention
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Continuous Glucose Meter System

In 2007, the FDA approved the STS-7 System, which monitors glucose levels every 5 minutes during a 7-day period. The STS-7 System, like other continuous glucose meter systems, is designed to be used in combination with traditional fingerstick tests and meters. It does not replace them. But the system can track trends and fluctuation patterns in blood sugar levels that fingerstick tests cannot detect.

Type 1 Diabetes Gene Discovered

In 2007, scientists announced the discovery of a gene that may increase the risk of developing childhood type 1 diabetes.

Anemia Drugs Warning

In 2007, following the publication of several studies in the New England Journal of Medicine, the FDA warned that erythropoiesis-stimulating drugs (used to treat anemia) can increase the risk for blood clots, strokes, and heart attacks when excessive doses are given. The FDA has set new dosing and hemoglobin target levels for these drugs. Anemia is a common complication of end-stage kidney disease.

Cell Transplantation Research

Islet cell transplantation using the Edmonton protocol is a promising treatment for type 1 diabetes, suggests a 2006 study published in the New England Journal of Medicine. The Edmonton protocol involves isolating islet cells from donor pancreases and then injecting the cells into the patient. In the first international multicenter trial of this investigational procedure, 44% of 36 patients were able to temporarily suspend insulin injections, while 28% achieved partial islet function.
Stem cell transplantation using cells harvested and re-infused from the patient’s own body may help increase beta cell function and eliminate the need for insulin injections, according to a small, preliminary study published in 2007 in the Journal of the American Medical Association.

Type 1 Diabetes Prevention Research

Scientists around the world are investigating new ways to prevent type 1 diabetes or at least delay its onset. Experimental preventive measures include treatment with oral insulin and with drugs that may prevent the immune system’s attack on beta cells.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes.

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 20 minutes after a meal insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (It should be noted that the brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and stomach. In addition to secreting digestive enzymes, the pancreas secretes the hormones insulin and glucagon into the bloodstream. The release of insulin into the blood lowers the level of blood glucose (simple sugars from food) by enhancing glucose to enter the body cells, where it is metabolized. If blood glucose levels get too low, the pancreas secretes glucagon to stimulate the release of glucose from the liver.

In type 1 diabetes, the disease process is more severe than with type 2 diabetes, and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival.

Type 2 diabetes is the most common form of diabetes, accounting for 90% of cases. About 20 million Americans have type 2 diabetes and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Maturity-Onset Diabetes in Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases.

Gestational Diabetes. An estimated 5% of pregnant women develop a form of type 2 diabetes in their third trimester called gestational diabetes. Gestational diabetes is usually temporary. [See In-Depth Report #60: Diabetes - type 2.]

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes, and others) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) also increase the risk for diabetes.

Causes

Type 1 diabetes is usually a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved.

Islets of Langerhans contain beta cells and are located within the pancreas. Beta cells produce insulin which is needed to metabolize glucose within the body.

Certain factors are thought to be important in this process:

White blood cells called T lymphocytes produce immune factors called cytokines that attack and gradually destroy the beta cells of the pancreas. Important cytokines are interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma.
Specific proteins are also critical in the process. They include glutamic acid decarboxylase (GAD), insulin, and islet cell antigens. These proteins serve as autoantigens. That is, they trigger the self-attack of the autoantibodies on the body's own beta cells.

Progression from the first stage, known as insulitis, to full-blown diabetes can take 7 years or longer. Unfortunately, by the time a person is aware that something is wrong and goes to the doctor with symptoms of type 1 diabetes, about 80 - 90% of the beta cells have been destroyed.

More than half of patients with insulitis do not develop diabetes. Researchers are greatly interested in discovering any factors that prevent the disease.

Researchers have found at least 18 genetic locations, labeled IDDM1 - IDDM18, that are related to type 1 diabetes. The IDDM1 region contains the HLA genes that encode proteins called major histocompatibility complex. The genes in this region affect the immune response. New advances in genetic research are identifying other genetic components of type 1 diabetes. In 2007, scientists announced that they had discovered a gene, KIAA0350, on chromosome 16. Variations in this gene appear to increase the risk of a child developing type 1 diabetes. The research team expects to identify an additional 15 - 20 genes associated with type 1 diabetes.

The odds of inheriting the disease, however, are only 10% if a first-degree relative has diabetes, and even in identical twins, one twin has only a 33% chance of having type 1 diabetes if the other has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.

Genetic factors cannot fully explain the development of diabetes. Over the past 30 years, a major increase in the incidence of type 1 diabetes has been reported in certain European countries, and the incidence has nearly tripled in the northeastern U.S. If genetic factors were the only cause of type 1 diabetes, such an increase in cases would take at least 400 years.

Some researchers believe one or more viral infections may trigger the disease in genetically susceptible individuals. Researchers suggest the following scenario:

An infection introduces a viral protein that resembles a beta-cell protein.
T cells and antibodies are tricked by this resemblance into attacking the beta protein as well as the virus.

Among the viruses under scrutiny are enteric viruses, which attack the intestinal tract. Coxsackieviruses are a family of enteric viruses of particular interest. (One study has suggested that respiratory infection in a child's first year, and not later, may be protective against diabetes, perhaps by priming the immune response so that it is better able to respond later on to other organisms.)

Risk Factors

An estimated 1 million people in the U.S. have type 1 diabetes, with about 30,000 new cases diagnosed each year. It is much less common than type 2, however, consisting of only 5 - 10% of all cases of diabetes. Nevertheless, like type 2 diabetes, the incidence of type 1 diabetes among children and adolescents has been rising over the past few decades. Experts estimate that about 1 in every 400 - 600 children and adolescents has type 1 diabetes. While type 2 diabetes has been increasing among African-American and Hispanic adolescents, the highest rates of type 1 diabetes are found among Caucasian youth.

Type 1 can occur at any age but usually appears between infancy and the late 30s, most typically in childhood or adolescence. Boys and girls are equally vulnerable. Studies report the following may be risk factors for developing type 1 diabetes:

Being ill in early infancy.
Early foods. Some studies have reported that early exposure to cow's milk in infancy and not being breast fed increased the risk for type 1 diabetes. Two studies in 2003 suggested that very early exposure to cereal -- not cow's milk -- plays a role in risk. Any risk from early dietary factors is still very low and likely to affect children who already have a genetically impaired immune response to dietary proteins. Breast milk contains factors that may help regulate the immune response and prevent diabetes in such children. National differences in risk also suggest that not all cow's milk is the same, and some proteins may confer higher risks than others.
Having a parent with type 1 diabetes.
Having an older mother.
Having a mother who had preeclampsia during pregnancy.
Obesity in children has long been linked to a higher risk for type 2 diabetes. Two 2001 studies reported an association between high weight at birth and obesity during childhood as risk factors for type 1 diabetes as well. The common risk factor may be an increase in insulin secretion, which occurs with obesity. This theoretically could overstress the beta cells so that they become susceptible to damage by overactive immune factors (particularly cytokines), and eventually to destruction in children genetically vulnerable to type 1 diabetes.

Until recently, diabetes in children was almost always type 1 diabetes. Of major concern, however, are estimates that between 8 - 45% of new diabetes cases in children are now type 2, most likely because of the increase in childhood obesity. [See In-Depth Report #60: Diabetes - type 2.]

The incidence of type 1 diabetes is higher than average among people with other autoimmune diseases, including Grave's disease, Hashimoto's thyroiditis (a form of hypothyroidism), Addison's disease, multiple sclerosis (MS), and pernicious anemia. Research has raised the possibility that all autoimmune diseases share a common genetic basis. A 2001 study found, for example, that the T-cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Both diseases have been associated with cow's milk protein. Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders or why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

There is a very wide variation in incidence of type 1 among population groups. Type 1 diabetes appears to be most common in people of northern European descent and in specific Mediterranean groups (such as Sardinians). It is less common among Asians and African-Americans. Still, African-Americans with type 1 diabetes are 50% more likely to die from it than Caucasians, mostly due to lower-quality health care.

Symptoms

The process that destroys the insulin-producing beta cells can be long and insidious. At the point when insulin production bottoms out, however, type 1 diabetes usually appears suddenly and progresses quickly. Warning signs of type 1 diabetes include:

Frequent urination (in children, a recurrence of bed-wetting after toilet training has been completed)
Unusual thirst, especially for sweet, cold drinks
Extreme hunger
Sudden, sometimes dramatic, weight loss
Weakness
Extreme fatigue
Blurred vision or other changes in eyesight
Irritability
Nausea and vomiting (acute symptoms)

Children with type 1 diabetes may also be restless, apathetic, and have trouble functioning at school. In severe cases, diabetic coma may be the first sign of type 1 diabetes.

Life-Threatening Complications

Diabetic ketoacidosis (DKA) is a life-threatening complication that develops when insulin stores are depleted. It is almost always caused by noncompliance with insulin treatments. Other contributing factors are lack of health insurance and intentionally reducing insulin levels in order to lose weight. In one study, adolescent girls were at higher risk for ketoacidosis than other groups of children and young people.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.

These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels. Symptoms and complications include:

Nausea and vomiting
Deep and rapid breathing may with frequent sighing
Rapid heartbeat
Cerebral edema, or brain swelling, is a rare but very dangerous complication that occurs in 1% of ketoacidosis cases and results in coma, brain damage, or death in many cases. Research now suggests that the risk for this complication is significantly higher in children with severe ketoacidosis (indicated by low carbon dioxide levels and high nitrogen urea levels), and possibly if they are also treated with bicarbonate to reduce acid levels.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.
If the condition persists, coma and eventually death may occur, although over the past 20 years, death from DKA has decreased to about 2% of all cases.

Life-saving treatment uses rapid rehydration with a salt (saline) solution followed by low-dose insulin and potassium replacement.

Ketoacidosis is a serious condition of glucose build-up in the blood and urine. A simple urine test can determine if high ketone levels are present.

Tight blood sugar (glucose) control increases the risk of low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, occurs if blood glucose levels fall below normal. Hypoglycemia may also be caused by insufficient intake of food, or excess exercise or alcohol. Usually the condition is manageable, but occasionally, it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms.

Risk Factors for Severe Hypoglycemia. Among young patients, the youngest children and boys of any age are at higher risk for hypoglycemia. Specific risk factors for severe hypoglycemia include:

Intensively controlling blood glucose and HbA1c levels
Having long-term diabetes
Being less educated about the condition
Being underinsured
Having psychiatric disorders

Hypoglycemia unawareness. Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks.

Nocturnal hypoglycemia (which occurs during sleep) is a common problem for children, even those on nonintensive insulin therapy. (The risk for hypoglycemia is high in any case in children.) Bedtime snacks are advisable if blood glucose levels are below 180 mg/dL (10 mmol/L). Protein snacks may be best. (The use of the insulin pump may help prevent hypoglycemic episodes.)
Some research has suggested that children (particularly thin children) are at higher risk for hypoglycemia because the injection goes into muscle tissue. Pinching the skin so that only fat (and not muscle) tissue is gathered or using shorter needles may help.
Various insulin regimens are available that can reduce the risk. For example, taking a fast-acting insulin (insulin lispro) before the evening meal may be particularly helpful in preventing hypoglycemia.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who are at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, possibly including the intravenous administration of a glucose solution.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see an example of a glucagon kit.

Experts have been concerned that the increased incidence of hypoglycemia accompanying strict blood glucose control could cause mental deterioration over time, but a 6-year study has found no evidence of this in adolescents and adults. (The effect on young children, however, is not known.)

Diagnosis

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diagnosing diabetes. It is a simple blood test taken after 8 hours of fasting. In general, results indicate the following:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the tests are normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they are tested in the morning.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT tests require that the patient not eat for at least 8 hours prior to the test.

The oral glucose tolerance test is used to diagnose diabetes. The first portion of the test involves drinking a special glucose solution. Blood is then taken several hours later to test for the level of glucose in the blood. Patients who have diabetes will have higher than normal levels of glucose in their blood.

Test for Glycated Hemoglobin. Another test examines blood levels glycated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycated hemoglobin is not currently used for an initial diagnosis, but it may be useful for determining the severity of diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycation.
Glycation affects a number of proteins, and elevated levels of glycolated hemoglobin is strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Testing for Insulin Resistance. Investigators hope that some day a simple test for insulin resistance will be available to identify people at risk for diabetes. Some research suggests that measuring insulin and triglyceride levels during a fasting period may predict a person's sensitivity to insulin.

Type 1 diabetes is characterized by the presence of a variety of antibodies that attack the islet cells. These antibodies are referred to as autoantibodies because they attack the body's own cells -- not a foreign invader. Blood tests for these autoantibodies can help differentiate between type 1 and type 2 diabetes.

Screening for Heart Disease. All patients with diabetes should be tested for high blood pressure (hypertension) and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

High blood pressure is strongly associated with diabetic nephropathy (kidney disease). In fact, patients with type 2 diabetes who show signs of microalbuminuria typically already have hypertension. Type 1 diabetes patients with microalbuminuria, on the other hand, usually have normal blood pressure readings in the doctor's office. A 2002 study using home monitors, however, found that in patients with type 1 diabetes, high systolic blood pressure during sleep often occurs before development of nephropathy. (Systolic pressure is the first and higher number in a blood pressure reading.) Home blood pressure monitoring, may help identify patients with type 1 diabetes who are at risk for kidney damage.

Click the icon to see an image of an ECG.

Screening for Kidney Damage. The earliest manifestation of kidney disease is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. Microalbuminuria is also a marker for other complications involving blood vessel abnormalities, including heart attack and stroke.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleaning the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 1 diabetes have an annual comprehensive eye exam, with dilation, to check for signs of retina disease (retinopathy). Patients at low risk may need exams only every 2 - 3 years.

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Dietary Goals and Exercise

The treatment goals for a diabetes diet are:

Achieve near-normal blood glucose levels. People with type 1 diabetes must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin now allow more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 – 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists
Fats should provide 25 – 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 – 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat

[See In-Depth Report #42: Diabetes diet.]

Weight gain is a potential side effect of intense diabetic control with insulin. Being overweight can increase the risk for health problems. On the other hand, studies suggest that more than one-third of women with diabetes omit or underuse insulin in order to lose weight. Eating disorders have become a serious problem within the general population and are especially dangerous in patients with diabetes. Some evidence suggests that they contribute to about 20% of cases of recurrent ketoacidosis in young women. Ketoacidosis is a significant complication of insulin depletion and can be life threatening.

Aerobic exercise has significant and particular benefits for people with type 1 diabetes. It increases sensitivity to insulin, lowers blood pressure, improves cholesterol levels, and decreases body fat. Because glucose levels swing dramatically during workouts, people with type 1 diabetes need to take certain precautions:

Monitor glucose levels carefully before, during, and after workouts.
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
To avoid hypoglycemia, inject insulin in sites away from the muscles they use the most during exercise.
Before exercising, avoid alcohol and if possible certain drugs, including beta-blockers, which increase the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates, especially in the form of pre-exercise snacks. Skim milk is particularly helpful. They should also drink plenty of fluids.
Good, protective footwear is essential to help avoid injuries and wounds to the feet.

Resistance or high impact exercises should be avoided. They can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet. Because patients with diabetes may have silent heart disease, they should always check with their doctors before undertaking vigorous exercise.

A 2006 study of over 19,000 children with type 1 diabetes found that regular physical activity helps improve blood sugar levels without increasing the risk of severe hypoglycemia. The researchers suggest that doctors recommend regular exercise for pediatric patients with type 1 diabetes.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Treatment

Insulin is essential for strict control of blood glucose levels in type 1 diabetes. Tight blood glucose control is the best way to prevent major complications in type 1 diabetes including those that affect the kidneys, eyes, nerve pathways, and blood vessels. Intensive insulin treatment in early diabetes may even help preserve any residual insulin secretion for at least 2 years.

There are, however, some significant problems with intensive insulin therapy:

There is a higher risk for low blood sugar (hypoglycemia).
Many patients experience significant weight gain from insulin administration, which may have adverse effects on blood pressure and cholesterol levels. It is important to manage heart disease risk factors that might develop as a result of insulin treatment.

A diet plan that compensates for insulin administration and supplies healthy foods is extremely important. [See In-Depth Report #42: Diabetes diet.] Pancreas transplantation eventually may be recommended for patients who cannot control glucose levels without frequent episodes of severe hypoglycemia.

The goal of intensive insulin therapy is to keep blood glucose levels as close to normal as possible. In one major study, even when levels were 40% higher than nondiabetic levels, benefits were still observed.


	Normal	Goal
Blood glucose levels before meals	Less than 110 mg/dL (or 6.1 mmol/L)	90 - 130 mg/dL (or 5 - 7.2 mmol/L)
Bedtime blood glucose levels	Less than 120 mg/dL (6.6 mmol/L)	110 - 150 mg/dL (or 6.1 - 8.3 mmol/L)
Glycated hemoglobin (HbA1c) levels	4 - 6%	Less than 7%
Source: National Diabetes Information Clearinghouse, National Institutes of Diabetes and Digestive and Kidney Diseases.

Standard insulin therapy usually consists of one or two daily insulin injections, one daily blood sugar test, and visits to the health care team every 3 months. For strictly controlling blood glucose, however, intensive management is required. The regimen is complicated although newer insulin forms may make it easier.

There are two components to flexible insulin administration and a number of variations of insulin delivery for accomplishing them:

Basal insulin administration. The basal component of the treatment attempts to provide a steady amount of background insulin throughout the day. Basal insulin levels maintain regular blood glucose needs. Insulin glargine now offers the most consistent insulin activity level, but other intermediate and long-acting forms may be beneficial when administered twice a day. Short-acting insulin delivered continuously using a pump is proving to a very good way to provide basal rates of insulin.
Mealtime insulin administration. Meals require a boost (a bolus) of insulin to regulate the sudden rise in glucose levels after a meal.

In achieving insulin control the patient must also take other steps:

The patient should perform four or more blood glucose tests during the day.
Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
Insulin requirements vary depending on many non-nutritional situations during the day, including exercise and sleep. People are at enhanced risk for low blood sugar during exercise. Some patients experience a sudden rise in blood glucose levels in the morning -- the so-called "dawn phenomenon."
The patient must also maintain a good diet plan and should visit the health care team of doctors, nurses, and dietitians once a month.

Because of the higher risk for hypoglycemia in children, experts recommend that intensive treatment be used very cautiously in children under 13 and not at all in very young children.

Insulin cannot be taken orally because the body's digestive juices destroy it. Injections of insulin under the skin ensure that it is absorbed slowly by the body for a long-lasting effect. The timing and frequency of insulin injections depend upon a number of factors:

The duration of insulin action. Insulin is available in several forms, including: standard, intermediate, long-acting, and rapid-acting.
Amount and type of food eaten. Ingestion of food makes the blood glucose level rise. Alcohol lowers levels.
The person's level of physical activity. Exercise lowers glucose levels.

Fast-Acting Insulin. Insulin lispro (Humalog) and insulin aspart (Novo Rapid, Novolog) lower blood sugar very quickly, usually within 5 minutes after injection. Insulin peaks in about 4 hours and continues to work for about 4 hours. This rapid action reduces the risk for hypoglycemic events after eating (postprandial hypoglycemia). Optimal timing for administering this insulin is about 15 minutes before a meal, but it can be also taken immediately after a meal (but within 30 minutes). Fast-acting insulins may be especially useful for meals with high carbohydrates.

Regular Insulin. Regular insulin begins to act 30 minutes after injection, reaches its peak at 2 - 4 hours, and lasts about 6 hours. Regular insulin may be administered before a meal and may be better for high-fat meals.

Intermediate Insulin. NPH (neutral protamine Hagedorn) insulin has been the standard intermediate form. It works within 2 - 4 hours, peaks 4 - 12 hours later, and lasts up to 18 hours. Lente (insulin zinc) is another intermediate insulin that peaks 4 - 12 hours and lasts up to 18 hours.

Long-Acting (Ultralente) Insulin. Long-acting insulins, such as insulin glargine (Lantus), are released slowly. Insulin glargine matches parts of natural insulin and maintains stable activity for more than 24 hours. Studies suggest that it poses less of a risk for hypoglycemia and weight gain than NPH. It has a higher incidence of pain at the injection site than NPH. Ultralente insulin peaks at 10 hours and lasts up to 20 hours but varies greatly in activity from day to day.

Combinations. Regimens generally include combinations of short and longer-acting insulins to help match the natural cycle. For example, one approach in patients who are intensively controlling their glucose levels uses 3 injections of insulin, which includes a mixture of regular insulin and NPH at dinner. Another approach uses 4 injections, including a separate short-acting form at dinner and NPH at bedtime, which may pose a lower risk for nighttime hypoglycemia than the 3-injection regimen.

Insulin Pumps. An insulin pump can improve blood glucose control and quality of life with fewer hypoglycemic episodes than multiple injections. The pumps correct for the “dawn phenomenon” (sudden rise of blood glucose in the morning) and allow quick reductions for specific situations, such as exercise. Many different brands are available.

The typical pump is about the size of a beeper and has a digital display. Some are worn externally and are programmed to deliver insulin through a catheter in the skin or the abdomen. They generally use rapid-acting insulin, the most predictable type. They work by administering a small amount of insulin continuously (the basal rate) and a higher dose (a bolus dose) when food is eaten.

Many adults, adolescents, and school children use insulin pumps. A 2006 study found that even very young children (ages 2 - 7 years) can successfully use insulin pumps and that the pumps provided better blood sugar control than twice-daily insulin injections.

The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes. Dosage instructions are entered into the pump's small computer, and the appropriate amount of insulin is then injected into the body in a calculated, controlled manner.

Learning to use the pump can be complicated, although over time most patients find the devices are fairly easy to use. To achieve good control, patients and parents of children must undergo some training. The patient and doctor must determine the amount of insulin used -- it is not automatically calculated. This requires an initial learning period, including understanding insulin needs over the course of the day and in different situations and knowledge of carbohydrate counting. Frequent blood testing is very important, particularly during the training period.

Insulin pumps are more expensive than insulin shots and occasionally have some complications, such as blockage in the device or skin irritation at the infusion site. In spite of early reports of a higher risk for ketoacidosis with pumps, more recent studies have found no higher risk.

Insulin Pens. Insulin pens, which contain cartridges of insulin, have been available for some time. Until recently, they were fairly complicated and difficult to use. Newer, prefilled pens (Humulin Pen, Humalog) are disposable and allow the patient to dial in the correct amount.

Inhaled Aerosol. In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

Other Alternative Insulin Delivery Methods. Another promising avenue of investigation for delivering insulin is the use of ultrasound pulses.

Pramlintide (Symlin) is a new type of injectable drug that can help control postprandial hyperglycemia, the sudden increase in blood sugar after a meal. Pramlintide is injected before meals and can help lower blood sugar levels in the 3 hours after meals. Pramlintide is used in addition to insulin for patients who take insulin regularly but still need better blood sugar control. The FDA approved this drug in 2005 for adults with type 1 and type 2 diabetes. Pramlintide and insulin are the only two drugs approved for treatment of type 1 diabetes.

Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Side effects may include nausea, vomiting, abdominal pain, headache, fatigue, and dizziness. Patients with type 1 diabetes have an increased risk of severe low blood sugar (hypoglycemia) that may occur within 3 hours following a pramlintide injection. This drug should not be used if patients have trouble knowing when their blood sugar is low or have slow stomach emptying (gastroparesis).

CD3-Antibodies. A new type of drug called a CD3 antibody is showing promise for helping patients newly diagnosed with type 1 diabetes. In phase II clinical trials, patients received the drug for 6 days. Results from a 2005 trial published in the New England Journal of Medicine indicated that the CD3 antibody helped stimulate the patients’ natural insulin production and decreased their need for insulin drug therapy. The beneficial effects lasted up to 18 months after CD3 treatment. Researchers think that this drug affects the autoimmune response involved in type 1 diabetes and helps preserve the residual beta cell function of the pancreas.

Monitoring Tests

Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to carefully monitor blood glucose levels. In general, patients with type 1 diabetes need to take readings four or more times a day. Patients should aim for the following measurements:

Pre-meal glucose levels of between 90 - 130 mg/dL
Bedtime levels of between 110 - 150 mg/dL

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Finger-Prick Test. A typical blood sugar test includes the following:

A drop of blood is obtained by pricking the finger.
The blood is then applied to a chemically treated strip.
Monitors read and provide results.

Home monitors are about 10 - 15% less accurate than laboratory monitors are and many do not meet the standards of the American Diabetes Association. Most doctors believe, however, that they are accurate enough to indicate when blood sugar is too low.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some simple procedures may improve accuracy:

Testing the meter once a month.
Recalibrating it whenever a new packet of strips is used.
Using fresh strips; outdated strips may not provide accurate results.
Keeping the meter clean.
Periodically comparing the meter results with the results from a laboratory.

Supplementary Monitoring Devices. Other devices are available for monitoring blood glucose. These devices are used in addition to traditional fingerstick test kits and glucose meters but do not replace them:

Continuous glucose monitoring systems (CGMS) use a needle-like sensor inserted under the skin of the abdomen to monitor glucose levels every 5 minutes. In 2007, the STS-7 System was approved. Using a disposable sensor, the STS-7 measures glucose levels for up to a week. An alarm will sound if glucose levels are too high or low. The older Minimed system measures glucose over a 72-hour period and has wireless communication between the monitor and an insulin pump.
GlucoWatch is a battery-powered wristwatch-like device that measures glucose by sending tiny electric currents through the skin, a technique called reverse iontophoresis. It is painless and has a warning device when detecting high glucose levels. It takes 2 hours to warm up, and the sensor pads need to be changed every day. Glucowatch measures glucose levels three times per hour for up to 12 hours. About a quarter of the time, the results differ significantly from actual fingerstick tests, however.

Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

Urine tests are useful for detecting the presence of ketones. These tests should always be performed during illness or stressful situations, when diabetes is likely to go out of control. The patient should also undergo yearly urine tests for microalbuminuria (small amounts of protein in the urine), a risk factor for future kidney disease.

Long-Term Complications

Type 1 diabetes reduces the normal lifespan by an average of 5 - 8 years. However, survival rates are improving in all ethnic groups and both genders. Longer survival rates are probably due to improvements in monitoring and tighter control of blood glucose. There are two important approaches to preventing complications from type 1 diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. This approach is proving to prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Blood glucose control helps the heart, but it is also very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Patients with type 1 diabetes have a 10 times greater risk of heart disease than healthy patients. Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes accelerate the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke.
In type 1 diabetes, high blood pressure (hypertension) usually develops if the kidneys become damaged. High blood pressure is another major cause of heart attack, stroke, and heart failure. Children with diabetes are also at risk for hypertension.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions ranges from 15 - 53%.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Click the icon to see an image of the kidney.

Results from the Diabetes Control and Complications Trial (DCCT) prove that intensive blood sugar control reduces the long-term risk of heart disease complications by 50%. The results indicate that intensive blood sugar control is even more important in reducing these risks than blood pressure- and cholesterol-lowering drugs. Original participants in the trial received intensive blood glucose control for 6 years during the 1980s. Researchers continued to follow these patients’ progress during the next 17 years. A follow-up study, published in 2005 in the New England Journal of Medicine, found that the benefits of tight blood glucose control persisted over time and halved the risk of heart attack, stroke, angina, or coronary artery disease.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin reduces the risk for blood clotting and may help protect against heart attacks. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Reducing Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. ACE inhibitors are especially helpful for patients with type 1 diabetes as they may help prevent kidney disease (nephropathy).

Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with type 2 diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances, including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor and generics), pravastatin (Pravachol), simvastatin (Zocor and generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received a 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms.

Although lowering LDL cholesterol is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combining a statin with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care.

Fibrates, such as gemfibrozil (Lopid) and fenofibrate (Tricor), are usually the first choice. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Treatment and Prevention of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. Research indicates that ACE inhibitors are the best class of blood pressure medications for delaying kidney disease and slowing disease progression in patients with type 1 diabetes. Angiotensin-receptor blockers (ARBs) are also very helpful.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy, the leading cause of end-stage renal disease (ESRD), occurs in about 20 - 40% of patients with diabetes. Patients with ESRD have 13 times the risk of death compared to other patients with type 1 diabetes. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color. On an encouraging note, a 2005 study in the Journal of the American Medical Association reported that the prognosis of end-stage renal disease has greatly improved during the last 4 decades for patients with type 1 diabetes. The outlook was best for patients who were diagnosed with diabetes at a young age (under 5 years old). In addition, the study found that fewer people with type 1 diabetes are developing ESRD.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Patients with end-stage kidney disease should be aware of the current controversies surrounding the dosing of these drugs.

In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia. In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk for blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the warning chest pain for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Pain-Relief Treatment for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief: They include:

Nonprescription analgesics, such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures, such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Studies indicate that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in up to 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot) and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole (LucRo) reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

Click the icon to see an image of foot inspection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Some treatments are as follows:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults ages 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2, although in one study over 20% had signs of retinopathy 6 years after diagnosis. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Click the icon to see an animation on diabetic retinopathy.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slow ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, depression, in turn, increases the risk for hyperglycemia and complications of diabetes, according to one study. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH); a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Diabetes and Pregnancy. Both temporary diabetes that occurs during pregnancy (gestational diabetes) and pregnancy in a patient with existing diabetes can increase the risk for birth defects. Studies indicate that high blood sugar levels (hyperglycemia) may affect the developing fetus as soon as it is conceived.

Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes large amounts of insulin. This combination of high fetal blood levels of insulin and glucose can have significant effects:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

In addition to endangering the fetus, diabetes also presents risks to the pregnant woman, particularly preeclampsia, which is a potentially dangerous condition involving very high blood pressure during pregnancy. Pregnant women with diabetes are also at greater risk for retinopathy.

Some recommendations for preventing complications include:

Intensive blood sugar control during pregnancy may reduce the risk for problems in the infant.
Monitoring blood glucose after meals may protect against preeclampsia more effectively than monitoring before meals.
Aerobic exercise before and during pregnancy can lower glucose levels. (All pregnant women, particularly those with diabetes, should check with their doctors before embarking on a rigorous exercise regimen.)
To prevent birth defects that affect the heart and nervous system, women with diabetes should take a higher dose of folic acid from the time of conception up to week 12 of pregnancy. They should also be checked for any heart problems.
Women with diabetes should have an eye examination during pregnancy and up to a year afterward.

Although there was some concern that short-acting insulin lispro might increase the risk for birth defects, the most recent evidence suggests that it does not. In fact, some experts believe it achieves a better outcome and should be preferred to regular insulin in pregnant women. More research is needed.

Effect on Estrogen. Diabetes appears to blunt some of the effects of estrogen, which may increase the risk for heart disease. Women with diabetes have a higher risk for early menopause, which, in one study, occurred at an average age of about 41 years.

Reproductive Cancers. Women with type 1 diabetes often have lumps in the breast that are benign but which make mammograms difficult to interpret. It is not clear whether these lumps are risk factors for breast cancer. One study indicated that women with diabetes have a higher risk for endometrial cancer and possibly for breast cancer.

Lack of Blood Glucose Control. Control of blood glucose levels is generally very poor in adolescents and young adults. Adolescents with diabetes are at higher risk than adults for ketoacidosis resulting from noncompliance. In a British study of young adults with type 1 diabetes, 15% were already hypertensive, and about half of these young people had signs of kidney damage. Young people who do not control glucose are also at high risk for permanent damage in small vessels, such as those in the eyes.

Self-Destructive Behaviors. One study found that young people with diabetes have a higher than average rate of suicidal fantasies. Although the actual rate of suicide was no higher than that of their nondiabetic peers, such thoughts are strongly associated with self-destructive behavior.

Of particular note, up to one-third of young women with type 1 diabetes have eating disorders and under-use insulin to lose weight. Anorexia and bulimia pose significant health dangers in any young person -- but they can be especially severe in people with diabetes.

Transplantation Procedures

Major advances in islet-cell transplantation are allowing more patients to come off insulin or reduce their use of it.

Major clinical trials are now using a specific islet-cell (also called beta-cell) transplantation procedure called the Edmonton protocol, which usually involves the following steps:

As soon as there are sufficient numbers of islets available for transplantation, the patient is given intravenous antibiotics and oral vitamins E, B6, and A.
A machine isolates islet cells taken from donor pancreases, generally from cadavers. Two or three organs are usually needed in order to supply enough islet cells to have any effect on insulin production. (This is a major limitation of the procedure.)
Once the islets have been isolated, they are injected directly in a major vein in the patient's liver.
The islets are carried to capillaries in the liver where they produce insulin.
Specific drugs, such as tacrolimus, sirolimus, or rapamycin (Rapamume), are used to suppress the immune system. (Unlike immunosuppressant drugs used in other transplantation procedures, these drugs do not contain steroids, which destroy islet cells.) Immunosuppressants are needed for the rest of the patient's life so that the body does not reject these foreign islet cells.
The procedure has to be performed two or more times over a period of 2 - 3 months. This generally requires multiple pancreas donors in order to achieve complete independence from insulin therapy. This is a major limitation to the procedure.

In 2006, the New England Journal of Medicine published the results of the first multicenter trial of the Edmonton protocol. The results indicated that this treatment may benefit some patients with severe type 1 diabetes. Of the 36 patients who underwent the transplant procedure, 44% no longer needed insulin injections a year after the final treatment. However, two-thirds of these insulin-independent patients needed to resume insulin injections within 2 years.

The Edmonton protocol achieved partial islet function in 28% of patients, which helped control hypoglycemic unawareness, a serious complication of diabetes. (In hypoglycemic unawareness, patients no longer recognize the symptoms of severe low blood sugar.) Even though these patients still needed insulin shots, they had better control of their diabetes. Researchers are continuing to work on refining the Edmonton protocol so that its benefits can be more sustainable and long lasting.

A major obstacle for the islet cell transplantation is the need for two or more donor pancreases to supply sufficient islet cells. Unfortunately, there are not enough pancreases available to make this procedure feasible for even 1% of patients. Researchers, then, are looking for alternative sources for islet cells. In one center, for example, researchers used pig islet cells as the donor source in children and did not administer immunosuppressant drugs. Half the children responded well to this approach. Another study reported that select patients may require only one donor.

Other research is focusing on umbilical cord cells, embryonic or adult stem cells, bone marrow transplantation, and other types of cellular therapies. These studies are still in very early stages, but experts predict that there will be major research advances in these fields in the coming years. A small, preliminary study published in 2007 in the Journal of the American MedicalAssociation looked at the effects of autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) in patients newly diagnosed with type 1 diabetes. AHST is an experimental treatment for type 1 diabetes. It involves treating a patient with high doses of drugs to suppress the immune system, then harvesting the patient’s own blood cells and re-infusing them back into the body. In the study, 14 out of 15 patients who underwent AHST were able to stop taking insulin shots.

Whole pancreas transplants and double transplants of pancreases and kidneys are proving to have a good long-term success rate for some patients with type 1 diabetes. The operations help to prevent further kidney damage, and long-term studies indicate that they may even eventually reverse some existing damage. There is some evidence that heart disease and diabetic neuropathy improve after pancreas transplantation (although not retinopathy). One 10-year study reported that survival rate at 10 years was 76%, and two-thirds of the patients had both pancreas and kidney function. Immunosuppressive drugs are needed lifelong with this procedure. Experts generally recommend transplants in cases of end-stage kidney failure or when diabetes poses more of a threat to the patient's life than the transplant itself.

Uncontrolled diabetes causes damage to many tissues of the body, including the kidneys. Kidney damage caused by diabetes most often involves thickening and hardening of the internal kidney structures. Strict blood glucose control may delay the progression of kidney disease in type 1 and type 2 diabetics.

Prevention

Fingerstick blood tests are now available that can test for autoantibodies that identify children who are at high risk for developing type 1 diabetes. At this time, however, there is no way to prevent type 1 diabetes, and all preventive therapies are investigative. Until there are ways to prevent the condition, such screening tests are expensive and provide little value.

Investigational approaches focus on preventing type 1 diabetes or at least delaying it as long as possible. Preventive measures are sometimes defined as primary and secondary:

Primary prevention attempts to preserve all beta cells before the disease process starts.
Secondary prevention aims to deter further beta cell destruction once it has started and before symptoms arise.

For primary prevention, one experimental approach involves oral insulin, which is taken as a pill once a day. Unlike insulin injections that lower blood sugar, oral insulin does not affect blood glucose levels because it is quickly broken down in the digestive system. It may, however, help calm the immune system and prevent its attack on beta cells. Another study is exploring whether docosahexaenoic acid (DHA), an omega-3 fatty acid, can help prevent development of autoimmune type 1 diabetes in newborns who are at high risk for the disease.

Secondary prevention focuses on preserving beta cells and their insulin-producing function. Researchers are exploring several treatments for patients who are newly diagnosed with type 1 diabetes. These experimental therapies include:

Rituximab (Rituxan), a monoclonal antibody drug used for treatment of rheumatoid arthritis and non-Hodgkin’s lymphoma, is being studied in patients with type 1 diabetes for its effects on disrupting the immune system’s attack on beta cells.
Immune-suppressing drugs, such as mycophenolate mofetil (MMF) alone or in combination with daclizumab (DZB), are used to prevent rejection in organ transplantation. Researchers hope that these drugs may be able to slow or stop the autoimmune disease process of type 1 diabetes.
CD3-antibody drug therapy is showing promise in retaining newly diagnosed patients’ natural insulin production and decreasing their need for insulin therapy.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.nei.nih.gov -- National Eye Institute
www.eatright.org -- American Dietetic Association
www.kidney.org -- National Kidney Foundation
www.diabetestrialnet.org -- Type 1 Diabetes International Clinical Trial Net
www.medicalert.org -- Bracelets or neck chain emblems with personal medical information
www.childrenwithdiabetes.com -- Children with diabetes online community

References

American Diabetes Association (ADA). Standards of medical care in diabetes. VI. Prevention and management of diabetes complications. Diabetes Care. 2007 Jan;30(Suppl 1):S15-24.

Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med. 2006 Nov 16;355(20):2071-84.

Hakonarson H, Grant SFA, Bradfield JP, Marchand L, Kim CE, Glessner JT, et al. A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. Nature. Published online 15 July 2007.

SEARCH for Diabetes in Youth Study Group , Liese AD, D'Agostino RB, Hamman RF, Kilgo PD, Lawrence JM, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006 Oct;118(4):1510-8.

Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R, Robertson RP, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006 Sep 28;355(13):1318-30.

Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006 Nov 16;355(20):2085-98.

Skyler JS. Cellular therapy for type 1 diabetes: has the time come? JAMA. 2007 Apr 11;297(14):1599-600.

Vardi M, Nini A. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus. Cochrane Database Syst Rev. 2007 Jan 24(1):CD002187.

Voltarelli JC, Couri CE, Stracieri AB, Oliveira MC, Moraes DA, Pieroni F, et al. Autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. JAMA. 2007 Apr 11;297(14):1568-76.

Writing Group for the SEARCH for Diabetes in Youth Study Group , Dabelea D, Bell RA, D'Agostino RB, Imperatore G, Johansen JM, et al. Incidence of diabetes in youth in the United States. JAMA. 2007 Jun 27;297(24):2716-24.

Review Date:
7/19/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Asthma in children and adolescents

FitSugar — Wed, 08 Oct 2008 17:35:28 -0700

In This Report

Highlights
Introduction
Causes
Prognosis
Risk Factors
Symptoms
Diagnosis
Treatment
Quick-Relief Medications...
Long-Term Relief Medication...
Other Treatments
Managing Asthma
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Warning

In 2007, the FDA requested the manufacturers of omalizumab (Xolair) to include a “boxed warning” emphasizing that this drug may cause a severe and life-threatening allergic reaction (anaphylaxis). Health care providers need to carefully observe patients for 2 hours after they receive an omalizumab injection. However, because an allergic reaction can occur up to 24 hours after the injection, patients need to know the signs and symptoms of anaphylaxis and how to self-administer emergency treatment. Omalizumab is approved for patients ages 12 and older who have moderate-to-severe asthma related to allergies.

Drug Approval

In 2006, budesonide/formoterol (Symbicort) was approved for patients age 12 years and older. Symbicort combines a corticosteroid and a long-acting beta2-agonist into a single inhaler.

Inhaled Corticosteroids

Inhaled corticosteroids may help reduce wheezing in young children with breathing problems, but they do not help prevent the development of asthma, according to several 2006 studies in the New England Journal of Medicine.
Inhaled corticosteroids work better than a corticosteroid/long-acting beta2-agonist combination or a leukotrine receptor antagonist drug in treating children with mild-to-moderate asthma, suggests a 2007 study in the Journal of Allergy and Clinical Immunology.

Long-Acting Beta2-Agonists

Long-acting beta2-agonist drugs such as salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer) may worsen asthma symptom severity and increase the risk for asthma-related death, indicates a 2006 review in the Annals of Internal Medicine.
Products that contain salmeterol and formoterol now have strengthened warning labels detailing these risks.

Childhood Asthma Statistics

Asthma death rates among children have largely declined since 1999 while doctors’ office visits for asthma treatment have more than doubled, indicates a recent report from the U.S. Centers for Disease Control and Prevention.

Introduction

The word asthma originates from an ancient Greek word meaning panting. Essentially, asthma is an inability to breathe properly. When any person inhales, the air travels through the following structures:

Air passes into the lungs and flows through progressively smaller airways called bronchioles. The lungs contain millions of these airways.
All bronchioles lead to alveoli, which are microscopic sacs where oxygen and carbon dioxide are exchanged.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Asthma is a chronic condition in which these airways undergo changes when stimulated by allergens or other environmental triggers. Such changes appear to be two specific responses:

The hyperreactive response (also called hyperresponsiveness)
The inflammatory response

These actions in the airway cause patients to cough, wheeze, and experience shortness of breath (dyspnea), the classic symptoms of asthma.

In the hyperreactive response, smooth muscles in the airways constrict and narrow excessively in response to inhaled allergens or other irritants. Airways in everyone's lungs respond by constricting when exposed to allergens or irritants but there are major differences in the hyperreactive response that occurs in people with asthma:

When people without asthma breathe in and out deeply, the airways relax and open in order to rid the lungs of the irritant.
When people with asthma try to take those same deep breaths, their airways do not relax but instead narrow, causing the patients to pant for breath. Smooth muscles in the airways of people with asthma may have a defect, perhaps a deficiency in a critical chemical that prevents the muscles from relaxing.

The hyperreactive stage is followed by the inflammatory response, which generally contributes to asthma in the following way:

The immune system responds to allergens or other environmental triggers by delivering white blood cells and other immune factors to the airways.
These so-called inflammatory factors cause the airways to swell, fill with fluid, and produce a thick sticky mucus.

Click the icon to see an image of a normal versus asthmatic bronchiole.

This combination of events results in wheezing, breathlessness, inability to exhale properly, and a phlegm-producing cough.

Inflammation appears to be present in the lungs of all patients with asthma, even those with mild cases, and plays a key role in all forms of the disease.

Causes

Asthma occurs in about 5 million American children. Each year about 200,000 of them are hospitalized. It is the most common chronic childhood illness. About half of all cases of asthma develop before the age of 10, and about 80% of patients develop symptoms before they are 5 years old.

The mechanisms that cause asthma are complex and vary among population groups and even individuals. For example, asthma in children is highly associated with allergies. However, only a minority of children with allergies have asthma, and allergic response cannot explain all cases of asthma. Other factors, such as genetics or environmental conditions are probably involved in the development of asthma. Most likely, several genes combine to make a child susceptible to environmental triggers, not only allergens but also possibly infections, dietary patterns, or air pollution. Physical factors, particularly having smaller lungs, affect the chances for later asthma.

Asthma and allergies often coexist, and the allergic response plays a strong role in childhood asthma. About 70 - 85% of children with asthma also have allergies. Some studies suggest that children who have allergies are also at greater risk for developing asthma as adults. A 2006 study found that children who are allergic to dust mites are three times more likely to later develop asthma than children who were not allergic.

However, the evidence is clearly mixed. Several other 2006 studies suggested that avoiding dust mites does not help prevent asthma and, in fact, early exposure to dust mites may even protect children from developing asthma and allergic responses. Some experts think that giving immunotherapy (“allergy shots”) to children with allergies may help prevent asthma development.

An asthma attack can be induced or aggravated by direct irritants to the lungs. Studies indicate that the more indoor allergens a child is allergic to, the higher the risk for severe asthma. Important irritants or allergens include the following:

Dust mites, specifically mite feces, which are coated with enzymes that contain a powerful allergen. These are the primary allergens in the home.
Animal dander. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems.
Molds.
Cockroaches. Cockroaches are major asthma triggers and may reduce lung function even in people without a history of asthma.
Pollen. An asthma attack from an allergic response to pollen is more likely to occur during extreme air changes, such as thunderstorms. Major weather changes, such as El Nino, can affect the timing of allergy seasons because they cause seasonal changes (and pollen) to start earlier.
Food allergies. About 8 - 10% of children with asthma also have food allergies. These children also appear to have a high risk for very serious reactions to such foods. In infants and toddlers, allergy to eggs appears to be a predictor of asthma.
Fossil Fuels. Certain chemicals may trigger allergic rhinitis. Some experts believe that refined fossil fuels, such as diesel fuel and particularly kerosene, may be important triggers for allergic rhinitis. In people who already have allergies or asthma, exposure to such fossil fuels may worsen symptoms.

The Allergic Response. The allergic process, called atopy, and its connection to asthma are not completely understood. It involves various airborne allergens or other triggers that set off a cascade of events in the immune system leading to inflammation and hyperreactivity in the airways. One description is as follows:

The conductor in an orchestra of immune factors that contribute to allergies and asthma appears to be a category of white blood cells known as helper T cells, in particular a subgroup called Th2 cells.
Th2 cells overproduce interleukins (ILs), immune factors that are molecular members of a family called cytokines, which are involved in the inflammatory process.
Interleukins 4, 9, and 13, for example, may be responsible for a first-phase asthma attack. These interleukins stimulate the production and release of antibody groups known as immunoglobulin E (IgE). (People with both asthma and allergies appear to have a genetic predisposition for overproducing IgE.)
During an allergic attack, these IgE antibodies can bind to special cells in the immune system called mast cells, which are generally concentrated in the lungs, skin, and mucous membranes. This bond triggers the release of a number of active chemicals, importantly potent molecules known as leukotrienes. These chemicals cause airway spasms, overproduce mucus, and activate nerve endings in the airway lining.
Another cytokine, interleukin 5, appears to contribute to a late-phase inflammatory response. This interleukin attracts white blood cells known as eosinophils. These cells accumulate and remain in the airways after the first attack. They persist for weeks and mediate the release of other damaging particles that remain in the airways.

Researchers are investigating the role that T cells play in asthma. T cells are white blood cells that are involved in the immune response. Researchers had focused on the T cell called type 2 helper (ThH2) cells. However, a 2006 breakthrough study in the New England Journal of Medicine suggested that a different type of T cell may play a stronger role in asthma than previously thought.

Researchers discovered that these cells, called natural killer T cells, are far more common in the lungs of people with asthma than in the lungs of healthy people. Natural killer T cells are very rare, but researchers found them in 60% of people with moderate-to-severe persistent asthma. While this research is preliminary, it may explain why corticosteroid drugs do not work well for some patients with asthma: Steroid drugs target Th2 and other inflammatory cells, not natural killer T cells. Researchers think that further investigation of natural killer T cells may lead the way to new types of asthma drugs. If these cells prove to be involved in asthma, then drugs that eliminate them might become an important new treatment.

Over the course of years the repetition of the inflammatory events involved in asthma can cause irreversible structural and functional changes in the airways, a process called remodeling. The remodeled airways are persistently narrow and can cause chronic asthma. Researchers are trying to determine how this process occurs:

Interleukins. Some researchers are looking at potent immune factors, including interleukins 11 and 13. They have been linked to a number of processes possibly involved in remodeling, including scarring in the airways and overgrowth of cells in the smooth muscles that line the airways.

Growth Factors. Compounds known as vascular endothelial growth factor (VEGF) have been observed in the airways of patients with asthma. VEGF is a powerful promoter of cell growth in blood vessel linings and some researchers believe it may be major factor in remodeling.

About one-third of all persons with asthma share this condition with another member of their immediate family. Asthma may be more likely to be passed to children from the mother than from the father. Both allergies and asthma are strongly associated with hereditary factors, sharing certain genetic markers, but they are not always inherited together.

Research on the genetics of these conditions is confusing. Of some significant promise, researchers have identified a gene (ADAM33), which has been linked to asthma. The gene regulates one of the enzymes called metalloproteases, which are involved with the smooth muscle in the airway. A mutation of this gene could play a role in airway changes that occur after inflammation.

The role of early childhood respiratory and intestinal infections is very complex. Viral respiratory infections certainly worsen existing asthma, but the most common ones are unlikely to be causes of childhood asthma. In fact, early respiratory and intestinal infections may offer some protection against asthma.

Early Respiratory Infections as Causes of Asthma. Studies suggest that most respiratory infections are not important causes of asthma in children, except in certain cases. An important exception is the respiratory syncytial virus (RSV), which has been implicated in the development of asthma. RSV is the major viral cause of infant pneumonia. Studies also indicate that infants who have reduced lung function within a few days after birth are at increased risk of developing asthma by the time they are 10 years old.

Common Respiratory Infections Worsen Asthma. Common respiratory infections viruses that cause colds (such as the rhinovirus) may in some cases be associated with the development of asthma. A 2007 study suggested that children who have a wheezing rhinovirus during infancy are at increased risk for developing asthma by age 6. Even if these viruses do not directly cause asthma, they can worsen asthma in children who already have it. Rhinovirus has been reported to be the most common infection associated with asthma attacks. In one study, it was associated with 61% of asthma worsening in children. Some research suggests that colds promote inflammation in patients with existing asthma and increase the intensity of airway responsiveness for weeks.

The Hygiene Theory: Early Infections as Protection Against Asthma. Another blames the dramatic increase in asthma on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. The basic theory rests on the idea that infections stimulate production of specific immune factors called Th1 cells. As these cells build up, they replace other immune factors called Th2 cells, which react to allergens -- a less serious threat to the body. Without infections to stimulate the production of the Th1 infection fighters, the Th2 allergen fighters are not replaced, and they persist at high levels, making the growing child more susceptible to allergies and asthma.

A number of different studies support this theory:

Some studies suggest that being part of a large family or attending day care increases the risk for early respiratory infections but reduces the risk of childhood asthma. The occasional cold, then, may be protective.
In one study, researchers measured levels of bacterial byproducts called endotoxins in the mattress dust of 812 children. Those with the highest levels had 80% lower rates in allergies and asthma.
Another study further found a strong association between allergy development and the absence of certain beneficial bacteria (called probiotics) carried in the infant's intestines. Infants who were born in more hygienic environments tended to lack these bacteria. Antibiotic overuse and modern hygiene may be reducing these helpful organisms. (Probiotics can be obtained in active yogurt cultures and in supplements, which are being studied for protection.)

The standard vaccinations against serious childhood infections, according to several important studies, pose no risk for asthma. One of the studies even reported some lower risk for asthma and allergies in the second and third years after vaccinations. Infections killed thousands of children every year before immunization became widespread. Asthma, although serious, is rarely fatal in children. No one should stop giving their children vaccinations against childhood killers.

GERD. At least half of patients with asthma also have gastroesophageal reflux disease (GERD), the cause of heartburn. It is not entirely clear which condition causes the other or whether they are both due to common factors.

Heartburn is a condition where the acidic stomach contents back up into the esophagus causing pain in the chest area. This reflux usually occurs because the sphincter muscle between the esophagus and stomach is weakened. Standing or sitting after a meal can help reduce the reflux which causes heartburn. Continuous irritation of the esophagus lining as in gastroesophageal reflux disease is a risk factor for the development of adenocarcinoma.

Some theories for the causal connection between GERD and asthma are:

Acid leaking from the lower esophagus in GERD stimulates the vagus nerve, which runs through the gastrointestinal tract. This stimulated nerve, in turn, triggers the nearby airways in the lung to constrict, causing asthma symptoms.
Acid back-up that reaches the mouth may be inhaled into the airways (aspirated). Here, the acid triggers a reaction in the airways that cause asthma symptoms.

GERD is sometimes hard to detect and might be suspected as a contributor in the following patients:

Those who do not respond to asthma treatments.
Those whose asthma attacks follow episodes of heartburn.
Those whose attacks are worse after eating or exercise.
Those whose coughs follow episodes of acid reflux. (One study found that GERD was associated with about half of the episodes of coughs and wheezes in patients with asthma.)

Treating GERD symptoms with anti-acid drugs may resolve asthma in some (but not all) patients who share both conditions. A small 2005 observational study found that while GERD was common in patients with asthma, treatment of GERD had no effect on asthma symptoms. [See In-Depth Report #85: Heartburn and gastroesophageal reflux disease.]

Sinusitis. Almost half of children and adults with allergic asthma have sinus abnormalities, and in various studies, between 17 - 30% of patients with asthma develop true sinusitis. The presence of sinusitis, however, does not appear to increase the severity of asthma.

Click the icon to see an image of sinusitis.

Parental Migraines and Childhood Asthma. Some studies have reported a link between childhood asthma and parental migraines, with one small study suggesting that children are about five times more likely to develop asthma if their parents have a history of migraines.

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath.

About 10% of adults and some fewer children have aspirin-induced asthma (AIA). With this condition, asthma gets worse when patients take aspirin. Aspirin is one of the drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs). Although aspirin is used to reduce inflammation in other disorders, it appears to have the opposite effect in many asthma cases. It is not wholly known why this occurs. AIA often develops after a viral infection. It is a particularly severe asthmatic condition and is associated with up to 25% of asthma-related hospitalizations. In about 5% of cases, aspirin is responsible for a syndrome that involves multiple attacks of asthma, sinusitis, and nasal congestion. Such patients also often have polyps (small benign growths) in the nasal passages.

Patients with aspirin-induced asthma (AIA) should avoid aspirin and most likely NSAIDs, including ibuprofen (Advil) and naproxen (Aleve).

Acetaminophen (Tylenol) has been the traditional alternative for relief of minor pain for patients who are aspirin-sensitive. Unfortunately, recent evidence has muddied these recommendations. Moreover, some asthmatic episodes have been linked to high consumption of acetaminophen among adults. And a study of children with asthma reported that those who took ibuprofen were less likely to be hospitalized for asthma than those taking acetaminophen. This is of particular concern, since acetaminophen is the pain reliever of choice in small children.

Asthma occurs primarily at night (nocturnal asthma) in as many as 75% of patients with the condition. Attacks often occur between 2 - 4 a.m. Factors that might play role in nocturnal asthma may include one or more of the following:

Chemical and temperature changes in the body during the night that increase inflammation and narrowing of the airways
Delayed allergic responses from exposure to allergens during the day
The wearing off of inhaled medications toward the early morning
An increase in acid reflux (back up of stomach acid) that causes airways to narrow
Postnasal drip that occurs during sleep
Conditions relating to sleep, such as sleep apnea or sleeping on one's back, which may worsen any asthma attack that occurs at night

Some experts believe that nocturnal asthma may actually be a unique form of asthma with its own specific biologic mechanisms that occur only at night and which reduce natural steroid hormones (which block inflammation).

Exercise-induced asthma (EIA) is a limited form of asthma in which exercise triggers coughing, wheezing, or shortness of breath. This condition generally occurs in children and young adults, most often during intense exercise in cold dry air. Symptoms are generally most intense about 10 minutes after exercising and then gradually resolve.

EIA is triggered only by exercise and is distinct from ordinary allergic asthma in that it does not produce a long duration of airway activity, as allergic asthma does. (However, some people have both forms of asthma.) People who have only EIA do not appear to require long-term maintenance therapy. A study of military recruits with EIA also reported that the condition does not hinder a person's overall physical performance.

Medications. Cromolyn, a mild anti-inflammatory drug, or short-acting beta2-agonists have been the treatments of choice for preventing EIA. Newer approaches for people who work out regularly include pretreatment with long-acting beta2-agonists, such as salmeterol (Serevent) or the regular use of inhaled corticosteroids.

Hints for Reducing EIA. EIA occurs only after exercise and is more likely to occur with regular paced activities in cold, dry air. The following are some suggestions for reducing its impact:

Warm-up and cool-down periods are important.
Patients with EIA might do better with activities that involve short bursts of exercise (tennis, football) than with exercises involving long-duration regular pacing (cycling, soccer, and distance running).
Breathing through a scarf or through the nose helps warm up the airways.
Restricting dietary salt might help reduce EIA.

Click the icon to see an image of exercise-induced asthma.

Prognosis

Asthma is the third major cause of hospitalization in children under age 15. The condition can be very serious in children, particularly those younger than age 5, because their airways are very narrow.

The severity of asthma is graded as mild intermittent and mild, moderate, and severe persistent. A patient in any of these categories, even mild intermittent, can still experience a severe and even life-threatening attack. According to one report, 30% of asthma deaths occur in patients with mild asthma.

Asthma is rarely fatal in children, with only 187 asthma deaths reported in 2002 in children under age 18. In fact, a 2006 study from the U.S. Centers for Disease Control and Prevention reported that asthma death rates for children have steadily declined since 1999. (During the same time, the number of doctor visits for asthma treatment more than doubled.) Even low mortality numbers are unacceptable, however, since asthma deaths are largely preventable.

Factors associated with an increased risk of death from asthma in children include:

Previous life-threatening episodes of asthma
Lack of adequate and ongoing health care. (Most likely the reason for the higher fatalities rates in minority children.)
Significant behavioral problems
Underestimating the severity of an acute attack poses the greatest threat. Unfortunately, one study of children found that nearly 40% of them were unaware of asthmatic symptoms when they occurred.

African American children have more than six times the death rate of Caucasians in the age groups of 4 years and younger and 15 - 24 years. Hispanic children also have a higher risk.

The following signs and symptoms may indicate a life-threatening situation:

As the chest labors to bring enough air into the lungs, breathing often becomes shallow.
Lacking sufficient oxygen, the skin becomes bluish.
The flesh around the ribs of the chest appears to be sucked in.
The patient may begin to lose consciousness.

Asthma often progresses very slowly to a serious condition or may develop to a fatal or near-fatal attack within a few minutes. It is very difficult to predict when an attack will become very serious. Early symptoms or lack thereof do not always reflect the ultimate severity of an attack. Some studies even suggest that people at high risk for fatal or near-fatal asthma attacks are those with poor awareness of their own reduced ability to breathe and who are slow in seeking help. Monitoring peak flow rates is, therefore, an important management component, since it provides a more accurate assessment of lung function than symptoms alone.

In a 2003 study, researchers followed people with asthma for longer than 30 years. About a third of children had outgrown their asthma in adulthood. In general, the more severe the childhood asthma, the greater the likelihood that it will persist. For example, only 23% of children who experienced wheezy bronchitis (wheezing during respiratory infections) suffered from frequent or persistent asthma in adulthood.

There is evidence that severe asthma can cause long-lasting damage and possibly permanent scarring in some patients. The risk for such injury is highest, however, when asthma strikes children in the first 3 - 5 years. There does not appear to be any significant risk for long-term lung damage for children who develop mild-to-moderate persistent asthma between ages 5 - 12. Children adapt well to living with asthma, and even with severe asthma they can function as well as healthy children in virtually all areas of life.

Studies are mixed over the effects of emotional disorders on the severity of asthma. One study indicated that parents of children with asthma may suffer greater psychological stress than their children. A 2000 study reported that mild-to-moderate asthma does not significantly affect the psychological well-being of most children ages 5 - 12. Teenagers and preteens may have particular difficulty coping with what they perceive as the social stigma of asthma. Parents and older children should not hesitate to seek help from support groups, doctors, friends, or family members. Support programs may help children to better manage their asthma and even reduce hospitalization.

Although there have been few studies on the effects of asthma on schooling, a 2000 study reported that nocturnal (nighttime) asthma affected school attendance and performance in children and work attendance in their parents.

Risk Factors

Asthma affects about 5 million American children between the ages of 5 - 14. Asthma has dramatically increased worldwide over the last few decades, in both developed and developing countries. From 1980 - 1994, asthma increased 160% in American children younger than 4 years and has also dramatically risen worldwide. Experts are puzzling over the cause of this phenomenon. Possible causes and risk factors that are suspects in the dramatic rise in asthma in children include:

Survival rates are now higher in low-birth-weight babies, who may be more susceptible to asthma.
Declining rates in nursing may be a contributor. Breast milk contains important anti-inflammatory substances, such as omega-3 fatty acids, which might protect against asthma.
Western dietary habits (which commonly include more fast foods and less fruits, vegetables, fiber, minerals, and other nutrients) may contribute to the development of childhood asthma.
Children are spending more time indoors watching television, playing video games, or using the computer and are, therefore, overexposed to indoor allergens.
The trend of making homes more energy-efficient may result in dust mites being trapped inside them.

Among younger children, asthma develops twice as frequently in boys as in girls, but after puberty it may be more common in girls.

Urban Life. Urban life is strongly associated with a higher risk. Although poverty plays a significant role, urban life has been associated with a higher risk for asthma in any income group and among both children and adults. In some urban areas, as many as 25% of children have asthma or show signs of wheezing. In fact, it may be greatly underdiagnosed in city children. A 1999 study reported that almost a third of children in inner-city kindergartens had asthma symptoms without a diagnosis of the disorder; 10% had actually been diagnosed with asthma, mainly because their symptoms were severe.

Ethnicity. Since 1980, asthma rates have risen the most dramatically among African American children, and they have significantly higher rates of asthma than Caucasian children. Hispanic children are also at higher risk. Both groups of minority children are more likely to have fatal asthma than Caucasian children.

Some studies indicate that the difference in risk exists simply because African Americans and other minority groups are more likely to live in urban areas. Poverty and lack of access to health care also play a role. However, Caucasian children who live in cities also face a high risk for asthma, and rural African American children do not.

Urban life and socioeconomic factors, however, may not fully explain the ethnic disparity.

Low Birth Weight. Infants of low birth weight are at higher risk for lung problems and asthma.

Winter Birth. Children born in the winter may have a greater risk for asthmatic allergies to cockroaches than children born at other times of the year.

Vitamin D. A 2006 study suggested a link between vitamin D intake during pregnancy and development of early childhood asthma. Pregnant women who had a higher intake of vitamin D were less likely to give birth to children who developed asthma.

Breast Feeding. Most studies on breastfeeding report some protection against wheezing and asthma in the first year of life. Breastfeeding has many other benefits for the child as well. The American Academy of Pediatrics recommends exclusively breastfeeding for the child's first 6 months of life.

Complications of Pregnancy. According to a 2000 study, complications of pregnancy, specifically those involving the mother's uterus (such as post-birth hemorrhage, pre-term contractions, insufficient placenta, and restricted growth of the uterus), are associated with an increased risk of childhood asthma. Another study reported that delivery procedures such as Cesarean section, the use of vacuum extraction or forceps also raised the risk of childhood asthma.

In both adults and children, the incidence of obesity and asthma has been increasing over recent years. Studies report a strong association between the two conditions. Some experts suggest that excess weight pressing on the lungs may trigger the hyperreactive response in the airways typical of asthma. Others believe that asthma leads to obesity by inhibiting physical activity, although several studies have found no difference in activity levels between people with or without asthma. Some studies suggest that many obese people may be misdiagnosed as having asthma when they are simply short of breath, possibly because of the increased effort required for breathing.

In any case, there is evidence that losing weight can relieve asthma symptoms. Some evidence also suggests that people who are overweight (body mass index greater than 25) have more difficulty getting their asthma under control. Weight loss in anyone who is obese and has asthma or shortness of breath reduces airway obstruction and improves lung function. [See In-Depth Report #53: Weight control and diet.].

Damp Homes. Studies suggest that children who live in damp homes have a much higher risk for asthma.

Mental Health. Research indicates that poor mental health of parents and children are significant predictors of more severe symptoms in childhood asthma. A 2000 study suggested that high stress levels can predict the onset and severity of asthma in children genetically at risk for the condition.

Symptoms

In children with asthmatic symptoms, it is important to first consider as a possible cause inhaled foreign objects such as peanuts; viral infections such as croup; and bacterial infections, which may be accompanied by high fever and progress rapidly. Any child who has frequent coughing or respiratory infections should be checked for asthma.

The classic symptoms of an asthma attack include:

Wheezing when breathing out is nearly always present during an attack. Usually the attack begins with wheezing and rapid breathing, and, as it becomes more severe, all breathing muscles become visibly active.
Shortness of breath (dyspnea). Shortness of breath is a major source of distress in patients with asthma, although severe dyspnea does not always reflect a serious attack or reduced lung function.
Coughing. In some people, the first symptom of asthma is a nonproductive cough.
Chest tightness or pain. Initial chest tightness without any other symptoms may be an early indicator of a serious attack.
Neck muscles may tighten, and talking may become difficult or impossible.
Rapid heart rate
Sweating
Chest pain occurs in about 75% of patients. It can be very severe, although its intensity is not necessarily related to the severity of the asthma attack itself.

The end of an attack is often marked by a cough that produces thick, stringy mucus. After an initial acute attack, inflammation persists for days to weeks, often without symptoms. (The inflammation itself must still be treated, however, because it usually causes relapse.)

Diagnosis

The doctor will consider a diagnosis of asthma if a child has a history of periodic attacks of shortness of breath, coughing, and wheezing, perhaps accompanied by tightness in the chest. The parent should describe the pattern of symptoms and possible precipitating factors, including:

Whether symptoms are more frequent during the spring or fall (allergy seasons)
Whether exercise, a respiratory infection, or exposure to cold air has ever triggered an attack
Any family history of asthma or allergic disorders such as eczema, hives, or hay fever

A number of disorders may cause some or all of the symptoms of asthma. Panic disorder can coincide with asthma or be confused with it. Other diseases that must be considered during diagnosis are pneumonia, bronchitis, severe allergic reactions, psychosomatic illnesses, and certain rare disorders (such as tapeworm and trichomoniasis).

If symptoms and a patient's history are indicative of asthma, the doctor will usually perform tests known as pulmonary function tests to confirm the diagnosis and determine the severity of the disease.

Using a spirometer, an instrument that measures the air taken into and exhaled from the lungs, the doctor will determine several values:

Vital capacity (VC), which is the maximum volume of air that can be inhaled or exhaled.
Peak expiratory flow rate (PEFR), commonly called the peak flow rate, which is the maximum flow rate that can be generated during a forced exhalation.
Forced expiratory volume (FEV1), the maximum volume of air expired in 1 second.

If the airways are obstructed, these measurements will fall. Depending on the results, the doctor will take the following steps:

If measurements fall, the doctor typically asks the patient to inhale a bronchodilator. This drug is used in asthma to open the air passages. The measurements are taken again. If the measurements are more normal, the drug has most likely cleared the airways, and a diagnosis of asthma is strongly suspected.
If measurement results fail to show airway obstruction, but asthma is still suspected, the doctor may perform a challenge test. It involves administering a specific drug (histamine or methacholine) that usually increases airway resistance only when asthma is present.

The patient may be given skin or blood allergy tests, particularly if a specific allergen is suspected and available for testing. Allergy skin tests may be the best predictive test for allergic asthma, although they are not recommended for people with year-round asthma.

One of the most common methods of allergy testing is the scratch test or skin prick test. The test involves placing a small amount of the suspected allergy-causing substance (allergen) on the skin (usually the forearm, upper arm, or the back), and then scratching or pricking the skin so that the allergen is introduced under the skin surface. The skin is observed closely for signs of a reaction, which usually includes swelling and redness of the site. With this test, several suspected allergens can be tested at the same time, and results are usually available within about 20 minutes.

Tests that either rule out other diseases or obtain more information about the causes of asthma include the following:

A complete blood count
Chest and sinus x-rays
Computed tomography (CT) scans. CT scans may be helpful in certain cases, such as for determining wall thickness in airways in patients who are difficult to treat, which could signify a higher risk for lung damage.
Examination of the patient's sputum for eosinophils (white blood cells that in high levels are associated with severe allergic asthma).
Researchers are investigating measurements of certain chemicals in sputum or exhaled air that indicate airway inflammation. Such chemical markers include nitric oxide and hydrogen peroxide. For example, high levels of nitric oxide may prove to be a simple and noninvasive way of diagnosing asthma.

Treatment

Treating an Acute Attack in the Hospital. An acute attack may require hospitalization. Laboratory tests, an electrocardiogram (ECG), and a chest x-ray are performed to determine lung function, oxygen levels, and other indications of severity or rule out other causes. Depending on the results, the following treatments may be given:

Beta2-agonists are the standard therapy. They are typically administered with a nebulizer (a device that administers the drug in a fine spray). Studies suggest, however, that even very small children may be able to use metered-dose inhalers (MDIs), which are just as effective and more convenient than nebulizers. (Intravenous delivery is not recommended in most cases.)
An anticholinergic drug (ipratropium) is sometimes added to improve symptoms.
A corticosteroid (commonly called a steroid) given within the first hour helps reduce the need for hospitalization. Steroids may be administered intravenously, as a shot, or orally. Children may respond well to oral steroids.
Oxygen is usually administered, and can be life saving in severe cases.
Infusions of magnesium sulfate open airways and are an important emergency treatment for adults. Its benefits for children need to be further demonstrated.
In life-threatening situations, the patient may require mechanical ventilation.

Antibiotics are not useful for asthma attacks if there is no strong evidence of the presence of a bacterial infection. Viral infections, most often colds and the flu, are more likely to trigger an asthma attack. In such cases, antibiotics are not helpful and may have adverse effects.

Discharge and Relapse After Hospitalization. It typically takes about 3 - 4 hours to determine if a patient can be safely sent home or if they need to stay. Patients are generally discharged when:

Symptoms are gone or minimal, and
The peak expiratory flow rate is 70% or more of the predicted rate

Despite reasonable precautions, between 12 - 16% of patients relapse within 2 weeks of leaving the hospital. Receiving a steroid shot at discharge or taking an oral corticosteroid for a few days can reduce this risk.

Avoiding allergens, following appropriate drug treatments, and home monitoring are key elements in preventing dangerous asthma attacks and hospitalization. In addition, good communication between the doctor and patient is a key factor in a successful management program.

Medications for asthma fall into two categories:

Rescue Medications. Medications that open the airways (bronchodilators, or inhalers) are used to quickly relieve any moderate or severe asthma attack. These drugs are usually short-acting beta-adrenergic agonists (beta2-agonists). Other drugs used in special cases include corticosteroids taken by mouth and anticholinergic drugs. None of these drugs have any effect on the disease process itself. They are only useful for treating symptoms.
Maintenance Medications. Simply coping with asthma symptoms without also controlling the damaging inflammatory response is a common and serious error. For adults and children over age 5 with moderate-to-severe persistent asthma, experts now recommend inhaled corticosteroids and long-acting beta2-agonists.

Parents can greatly reduce the frequency and severity of their children’s asthma attacks by understanding the difference between coping with asthma attacks and controlling the disease over time. Unfortunately, many patients do not understand the difference between medications that provide rapid, short-term relief and those that are used for long-term symptom control. Many patients with moderate or severe asthma overuse their short-term medications and underuse their corticosteroid medications. The overuse of bronchodilators can have serious consequences; not using steroids can lead to permanent lung damage.

Patients need to understand that asthma symptoms can change quickly over time and that treatment strategies may need to change in response. In 2005, the two leading U.S. allergy associations published joint guidelines on controlling asthma. The guidelines emphasize that asthma treatment decisions need to be made on an individual basis. It is important that patients have a close relationship with their doctor. The doctor needs to evaluate a patient’s asthma symptoms at each visit to determine any need for changes in medication. According to the guidelines, asthma management is classified as either “well-controlled” or “not well-controlled.” The doctor may need to change some medications, or increase or decrease the dosage, depending on whether a child’s asthma is well-controlled or not well-controlled.

These are the signs of well-controlled asthma:

Asthma symptoms occur twice a week or less
Rescue bronchodilator medication is used twice a week or less
Symptoms do not cause nighttime or early morning awakening
Symptoms do not limit work, school, or exercise activities
Peak flow meter readings are normal or the patient’s personal best
Both the doctor and the patient consider the asthma to be well controlled


Classification	Symptom Frequency	Children Age 5 Years and Younger: Recommended Treatment	Children Older Than 5 Years: Recommended Treatment
Mild intermittent	At least 2 days per week. At least 2 nights per month.	No daily medication.	No daily medication. If severe attacks occur, systemic corticosteroids recommended.
Mild Persistent	More than 2 days per week, but less than once per day. More than 2 nights per month.	Preferred treatment: Low-dose inhaled corticosteroids with nebulizer, or MDI with holding chamber with or without face mask. Alternative treatment: Cromolyn or leukotriene-antagonist.	Preferred treatment: Low-dose corticosteroids. Alternative treatment: Cromolyn, leukotriene modifier, nedocromil, OR sustained release theophylline.
Moderate Persistent	Daily daytime symptoms. More than 1 night per week.	Preferred treatment: Low-dose inhaled corticosteroids and long-acting beta2-agonists OR medium-dose inhaled corticosteroids. Alternative treatment: Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (especially if severe attacks occur): Medium-dose inhaled corticosteroids and long-acting beta2-agonists; medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline.	Preferred treatment: Low-to-medium dose inhaled corticosteroids and long-acting beta2-agonists. Alternative treatment: Low-to-medium dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline, or increased medium dose inhaled corticosteroids. If needed (especially if severe attacks occur): Increase dosage of medium-dose inhaled corticosteroids with add-on long-acting beta2-agonists. Alternatively, increase dosage of medium-dose inhaled corticosteroids plus either leukotriene receptor antagonist or theophylline.
Severe Persistent	Continual daytime symptoms. Frequent nighttime symptoms.	Preferred treatment: High-dose inhaled corticosteroids and long-acting beta2-agonists plus (if needed) oral corticosteroids.	Preferred treatment: High-dose inhaled corticosteroids combined with long-acting inhaled beta2-agonists. Add, if needed: Oral corticosteroids. Repeat attempts should be made to reduce use of systemic corticosteroid and maintain control with inhaled corticosteroid.
Adapted from National Asthma Education and Prevention Program (NAEPP) Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma – Update on Selected Topics 2002 (EPR-2 Update).

Most asthma drugs are inhaled using various forms of inhalers or nebulizers. Inhaled drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Studies suggest that many children fail to use the devices properly, although newer devices are easier to use than others. The basic devices are the metered-dose inhaler (MDI), breath-actuated inhalers, dry powder inhalers, and nebulizers.

MDIs have used chlorofluorocarbons (CFCs) as their propellants. CFCs are damaging to the environment and are now being replaced with other propellants (hydrofluoroalkane) that are more environmentally safe, and do not chill the device as CFCs do. Devices that don't use any propellants are also now available.

Metered-Dose Inhaler. The standard device for administering any asthma medication is the metered-dose inhaler (MDI). This device, particularly when used with a spacer, allows precise doses to be delivered directly to the lungs. (The spacer is a tube that is attached to the inhaler. It serves as a holding chamber for the medication that is sprayed by the inhaler.) MDI-delivered drugs must be used regularly as prescribed and the patient carefully trained in their use in order for them to be effective and safe. Some patients hold the MDI too close to their mouths, or even inside them. Others may exhale too forcefully before inhalation.

The spacer helps improve medication delivery by allowing the patient additional time to inhale. They vary, however, in their effectiveness. It should be noted that MDIs can continue to deliver propellant even after the drug has been used up. Patients should track their medicine and throw the device away when the last dose has been administered.

Nebulizers (not MDIs) are typically used in very small children, both at home and in the emergency room. However, recent studies suggest spacers may be better than nebulizers for children and shorten the time spent in emergency rooms. Studies also indicate that with the use of a face mask and a spacer, the MDI works well even for infants in the emergency room and may prove to be useable at home.

Click the icon to see an illustrated series detailing a metered dose inhaler.

Breath-Actuated Inhalers. Breath-actuated rotary inhalers (Easi-Breathe and Autohaler) deliver the drug directly to the back of the throat as the user inhales. Their primary advantage over the MDI is their ease of use. They also do not use CFCs as propellants. In comparison studies, patients have been very successful with the breath-actuated inhalers. They are not recommended for children under 8 years old.

Dry Powder Inhalers. Dry powder inhalers (DPIs) deliver a powdered form of beta2-agonists or corticosteroids directly into the lungs. Such devices include Rotahaler, Spinhaler, Turbohaler, Clickhaler, Easyhaler, Diskhaler, Discus, Twisthaler, Spiros, and others. DPIs are as effective as the older devices, and generally have a better taste and are easier to manage. They may differ among themselves, however, in their ability to deliver drugs into the airways. In one study, for example, the Turbohaler was easier to use than the Diskhaler and so achieved better delivery.

Humidity or extreme temperatures can affect DPIs' performance, so they should not be stored in humid places (bathroom cabinets) or locations subject to high temperatures (glove compartments during summer months).

Dry-powder may cause tooth erosion. Children are advised to rinse their mouths out right after using these inhalers and to brush twice a day with a fluoride toothpaste.

Other Hand-Held Inhalers. Respimat delivers a fine-mist spray that is created by forcing the liquid medication through nozzles. It does not use any propellant.

Nebulizers. A nebulizer is a machine that delivers a fine spray of medication-containing liquid. Nebulizers are often used for children younger than 3 years and sometimes for older children who have difficulty using the MDI. It takes 5 - 10 minutes to administer medication using a nebulizer. Because the spray is less targeted than with the inhaler, it must deliver large amounts of the drug. This increases the risk for toxicity and severe side effects. Nebulizers should not be used by children who can manage an inhaler. Their use has been associated with a higher rate of hospitalizations and longer duration of symptoms than inhalers. A 2007 study also suggested that the misuse of home nebulizers may be an important factor in asthma deaths in children and young adults. If children must use an albuterol nebulizer, parents should be sure that it does not contain the preservative benzalkonium, which actually narrows the airways.

Click the icon to see an illustrated series detailing the use of a nebulizer.

Asthma triggers a vicious emotional-physical cycle:

Breathlessness and wheezing incite a fear of suffocation and death, even in very small children.
This anxiety produces further constriction on the muscles surrounding the airways, which makes breathing even more difficult.

Caregivers must first focus on alleviating their own anxiety, which can heighten a child's own fears. The next step is to help the child relax. One method for this is as follows:

The child sits comfortably, bending slight forward with the eyes closed.
The hands are placed gently over the navel.
The child is then told to pretend the stomach is a balloon.
The "balloon" must be "blown up" by inhalation, not exhalation. The child can tell if this working because the hands will move slightly apart.
When the child breathes out, the "balloon" will be made flat.

This exercise both relaxes the child and discourages shallow, oxygen-poor breathing. Massaging the child in gentle circles on the chest is relaxing and may also loosen mucus.

Other recommendations include:

A child may also find relief by lying stomach-down on several pillows so that the head is slightly lower than the chest while the caregiver gently pats the back between the shoulder blades.
Warm liquids, such as soup or hot cider, are effective in loosening mucus and may also relax bronchial muscles. Cold fluids, like cold air, should be avoided.
Overhydration (too much liquid) can be harmful, however, so these drinks should not be forced on the child.
Warm, moist air from vaporizers can greatly ease and moderate asthma attacks.
Daily massages and breathing and relaxation techniques to reduce stress can be very helpful.

Many adults self-manage their asthma using daily monitoring of peak air flow with adjustments of the medications as needed. This involves the use of a peak flow meter, which measures peak expiratory flow rate (PEFR).

Click the icon to see an image of a peak flow meter.

Studies suggest, however, that for most children with asthma, an educational program is just as effective for managing the condition as monitoring. Most children do not need to monitor their peak air flow on any regular basis.

Quick-Relief Medications

These medications quickly control acute asthma attacks.

Beta2-agonists do not reduce inflammation or airway responsiveness but serve as bronchodilators, relaxing and opening constricted airways during an acute asthma attack. A short-acting inhaled beta2-agonist, taken as needed, is often the only medication used by children with chronic mild asthma.

Asthma is a disease in which inflammation of the airways causes airflow into and out of the lungs to be restricted. When an asthma attack occurs, mucus production is increased, muscles of the bronchial tree become tight, and the lining of the air passages swells, reducing airflow and producing the characteristic wheezing sound.

Specific short-acting beta2-agonists include:

Albuterol (Proventil, Ventolin), called salbutamol outside the U.S., is the standard short-acting beta2-agonist in America. Other similar beta2-agonists are isoproterenol (Isuprel, Norisodrine, Medihaler-Iso), metaproterenol (Alupent, Metaprel), pirbuterol (Maxair), terbutaline (Brethine, Brethaire, Bricanyl), and bitolterol (Tornalate). Isoetharine (Bronkometer, Bronkosol) is available in nebulizers.
Newer beta2-agonists, including levalbuterol (Xopenex), have more specific actions than the standard drugs. Xopenex is administered with a nebulizer, and studies have indicated that it is as effective as albuterol with fewer side effects. The original formulation of Xopenex was administered with a nebulizer. A new metered-dose inhaler formulation was launched at the end of 2005. It is approved for children age 4 years and older.

Short-acting bronchodilators are generally administered through inhalation and are effective for 3 - 6 hours. They relieve the symptoms of acute attacks, but they do not control the underlying inflammation. If asthma continues to worsen with the use of these drugs, a doctor may prescribe corticosteroids or other drugs to treat underlying inflammation.

Side Effects of Beta2-Agonists. Side effects of all beta2-agonists may include:

Anxiety
Tremor
Restlessness
Headache
Fast and irregular heartbeats. A doctor should be notified immediately if this side effect occurs.
These drugs should be taken with caution by children with diabetes or a history of seizures.
Beta2-agonists have serious interactions with certain drugs and parents should tell the doctor about any other medications their child is taking.

Loss of Effectiveness and Overdose. There has been some concern that short-acting beta2-agonists become less effective when taken regularly over time, increasing the risk for overuse. Over time, some patients may become tolerant to many effects of short-acting beta2-agonists. The degree to which this affects the airways is uncertain. In some studies, the duration of action has declined but the peak effect appears to be preserved, making these drugs still useful for acute attacks. Regular use of long-acting beta2-agonists may increase the chances of a reduced effect from the short-acting forms.

A 2005 landmark study suggested that patients’ differing clinical response to albuterol may be based on their genotype. Albuterol targets the beta-adrenergic receptor. In the Beta-Adrenergic Response by Genotype (BARGE) trial, researchers studied the effects of albuterol on patients with two different forms of this receptor. The results suggested that patients with the arginine form of the receptor did not respond to albuterol. These patients’ asthma symptoms actually improved when albuterol was not used. By contrast, patients with the glycine form of the receptor had improved asthma control with albuterol.

Inhaled ipratropium bromide (Atrovent) acts as a bronchodilator over time. Ipratropium bromide alone is only modestly beneficial for acute asthma attacks. In fact, the drug is not approved specifically for asthma. Some parents report benefit for treating wheezing in infants. It is also sometimes used in the emergency room to treat children with severe asthma to enhance the effects of intravenous beta2-agonists.

Common oral corticosteroids include prednisone/prednisolone, dexamethasone, methylprednisolone, and hydrocortisone. They reduce inflammation very effectively. A 2006 study indicated that oral prednisolone worked better than inhaled fluticasone for treating mild-to-moderate asthma attacks in children in emergency rooms. However, children often have difficulty taking these drugs because they have a bitter taste and can cause vomiting. Taking oral dexamethasone for 2 days may be as effective and more tolerable than the standard 5-day regimen of prednisone/prednisolone. Prolonged use of oral steroids has widespread and sometimes serious side effects, so they are not generally give to children for longer than a few days.

[See In-Depth Report #4: Asthma in adults.]

Long-Term Relief Medications

These medications are taken on a regular basis to prevent asthma attacks and control chronic symptoms.

Corticosteroids, also called glucocorticoids or steroids, are powerful anti-inflammatory drugs. Steroids are not bronchodilators (they do not relax the airways) and have little effect on symptoms. Instead, they work over time to reduce inflammation and prevent permanent injury in the lungs. They can also help prevent asthma attacks from occurring. Many studies have shown that the use of inhaled corticosteroids in patients with moderate-to-severe asthma significantly reduces the rate of rehospitalizations and deaths from asthma.

Inhalation of corticosteroids makes it possible to provide effective local anti-inflammatory activity in the lungs with minimal systemic effects. (By contrast, oral steroids have considerable side effects throughout the body.) Inhaled corticosteroids are recommended as the primary therapy under the following circumstances:

For any asthmatic condition more serious than occasional episodes of mild asthma. (Low-doses of inhaled steroids may even be safe and effective for some people with mild asthma, particularly those who find themselves using beta2-agonists daily.)
When treatment with bronchodilators is not effective.

Examples of inhaled corticosteroids:

Inhaled steroids include fluticasone (Flovent), budesonide (Pulmicort), triamcinolone (Azmacort and others), and flunisolide (AeroBid). In general, the newer drugs are more powerful than the older generation of inhaled drugs. Budesonide (Pulmicort Respules) is available in a jet nebulizer for children from 12 months to 8 years. It is the first such medication to be approved for children in this age group.
The FDA approved a new inhaled corticosteroid, mometasone furoate (Asmanex) was approved in 2005 for patients age 12 and older.
The older corticosteroid inhalants are beclomethasone (Beclovent, Vanceril) and dexamethasone (Decadron Phosphate Respihaler and others). They are less powerful than the newer steroids when delivered with standard inhalers. New inhalers that use very fine sprays (QVAR, Autohaler) to deliver the drugs deep into the lungs may prove to be as effective as the newer, more potent steroids.
Inhalers that combine both long-acting beta2-agonists and corticosteroids are also available. These include Symbicort (budesonide/formoterol), which was approved in 2006 for patients ages 12 years and older.

Expert guidelines recommend inhaled corticosteroids as the preferred first-line therapy for children with mild-to-moderate asthma. Nevertheless, they are still significantly underprescribed in the patients who need them most. An important 2007 study of 6 - 14 year old children with asthma compared inhaled corticosteroid therapy (fluticasone) with an inhaled corticosteroid/long-term beta2 agonist (fluticasone/salmeterol) and a leukotrine receptor antagonist (montelukast). The results indicated that fluticasone alone worked better than the other two treatments.

Researchers have been investigating whether early treatment with corticosteroids can help prevent the development of asthma in at-risk children. Two important 2006 studies in the New England Journal of Medicine suggested that while inhaled corticosteroids helped ease symptoms and reduce breathing problems in pre-school children at risk for asthma, they did not help protect against asthma development.

For now, experts caution against corticosteroids for infants and toddlers with mild asthma and urge close monitoring especially for children under age 5 with severe asthma who are receiving high doses. Because the newer potent drugs, particularly fluticasone, may produce major side effects similar to oral steroids, it is important when treating all children to aim for the lowest effective dose possible. Fortunately, studies suggest that low doses of fluticasone may achieve the same benefits as with high ones, thus reducing risks for serious side effects. Better delivery methods may also allow lower doses.

Side effects of inhaled steroids may include:

The most common side effects are throat irritation, hoarseness, and dry mouth. These effects can be minimized or prevented by using a spacer device and rinsing the mouth after each treatment.
Rashes, wheezing, facial swelling (edema), fungal infections (thrush) in the mouth and throat, and bruising are also possible but not common with inhalators.
Some children experience changes in mood, memory, and behavior. These changes are not permanent.
Some studies have suggested a higher risk for gum inflammation.
Oral steroids reduce bone density. Research reports that inhaled steroids -- both older and newer drugs -- may also affect bone growth and density. However, a number of studies report only a slight effect (about half an inch) on children's growth, which may be only temporary. It is still unknown if these drugs have any significant long-term effect on bone density. Calcium supplements may help prevent bone loss that is due to inhaled steroids.
It is not yet known whether inhaled steroids affect lung growth in very young children. Steroids administered using nebulizers are of particular concern.
There is also some concern that the stronger drugs, particularly fluticasone, suppress the adrenal system to a greater degree than other steroid inhalants. This effect, in turn, reduces levels of natural steroids -- notably cortisol, the major stress hormone. (This is a serious side effect of oral steroids).

Long-acting beta2-agonists are used in combination with inhaled corticosteroids for treating children with moderate-to-severe asthma. These drugs include include salmeterol (Serevent Diskus) and formoterol (Foradil Aerolizer). A single inhaler (Advair Diskus) that combines both salmeterol and the corticosteroid fluticasone is available for children age 4 years and older, and an inhaler (Symbicort) combining formoterol and the corticosteroid budesonide is approved for children age 12 years and older.

Long-acting beta2-agonists are used for preventing an asthma attack (not for treating attack symptoms). The effects of one dose of a long-acting beta2-agonist last for about 12 hours, so they are particularly effective during the night. These drugs also may be used for prevention of exercise-induced asthma in people and to protect against aspirin-induced asthma.

However, research indicates that long-acting beta2-agonists can worsen asthma by increasing symptom severity. These drugs may also increase the risk for asthma-related deaths. Experts are still trying to determine when long-acting beta2-agonists should be added to an asthma treatment plan. If a child’s symptoms do not improve or if symptoms worsen with this type of drug, the doctor will recommend discontinuing it. Patients should not, however, stop taking this drug or other asthma medications without first talking with their doctors.

Side Effects. Side effects of long-acting beta2-agonists are similar to the short-acting drugs.

Specific Warning on Salmeterol and Formoterol. In 2003 a "black box" warning was added to product packaging for drugs that contain salmeterol, including Serevent Diskus, and Advair Diskus. Serevent and Advair are approved for patients age 12 years and older. The warning was based on a study that demonstrated more serious and even fatal asthma episodes in patients who used the drug than in patients who used a placebo.

In 2006, the FDA updated the warning to include formoterol (Foradil Aerolizer, approved for patients 5 years and older). Warnings for salmeterol and formoterol products emphasize that these medicines can increase the risk of severe asthma episodes. Long-acting beta2-agonists require up to 20 minutes to achieve effectiveness, and there is a danger of overdose if a patient is not aware of this delay and takes additional doses to achieve faster relief. The FDA recommends that patients:

Use long-acting beta2-agonists only if other medicines (such as steroids) have not helped control asthma.
Use a short-acting bronchodilator, not a long-acting beta2-agonist, to treat sudden wheezing.
Do not use long-acting beta2-agonists to treat wheezing that is getting worse. Call your doctor if this situation occurs.
Do not stop using any asthma medicines without first talking to your doctor.

Cromolyn sodium (Intal) is both an anti-inflammatory drug and has antihistamine properties that block asthma triggers such as allergens, cold, or exercise. Cromolyn has been the anti-inflammatory drug of choice for prevention of asthma attacks in children over age 4 with chronic moderate asthma. It is not as effective as inhaled corticosteroids, however, for reducing hospitalization rates, improving symptoms, and reducing the use of beta2-agonists in children with persistent asthma. Still, cromolyn has a well-known long-term safety record, while the long-term adverse effects of corticosteroids in children are still not fully known. Many children who need asthma maintenance therapy will still do well on cromolyn. (It may not provide any real benefit for children under age 4.)

Nedocromil (Tilade) is similar to cromolyn and needs to be taken only once a day. It also prevents asthmatic reactions to cold and exercise. It is not used in very young children. A cromolyn nasal spray called Nasalcrom has been approved for over-the-counter purchase, but only to relieve nasal congestion caused by allergies. Patients should not use it for self-medication without the advice of a doctor.

Side Effects. Side effects of cromolyn include nasal congestion, coughing, sneezing, wheezing, nausea, nosebleeds, and dry throat. Nedocromil has an unpleasant taste, and some people have complained of nausea, headache, and spasms in the airways, but no serious side effects have been reported.

Leukotriene-antagonists (also called anti-leukotrienes or leukotriene modifiers) are oral medications that block leukotrienes. Leukotrienes are powerful immune system factors that, in excess, produce a battery of damaging chemicals that can cause inflammation and spasms in the airways of people with asthma. As with other anti-inflammatory drugs, leukotrienes are used for prevention and not for treating acute asthma attacks.

Leukotriene-antagonists include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). These drugs are proving helpful for long-term prevention of asthma, including exercise-induced asthma and aspirin (or NSAID) -induced asthma. However, most studies to date have reported better success with inhaled corticosteroids than with the leukotriene-antagonists. A 2006 study of children with mild-to-moderate persistent asthma indicated that the corticosteroid fluticasone worked better than the leukotriene-antagonist montelukast in controlling symptoms. Nevertheless, some studies suggest that montelukast, which comes in a chewable tablet, may be particularly useful for managing asthma in small children (ages 2 - 5), since they have trouble with inhaled steroids.

Side Effects and Complications. Gastrointestinal distress is the most common side effect of leukotriene-antagonists. Very few other side effects have been reported. In general, these drugs appear to be safe and well-tolerated.

Of some concern are reports of Churg-Strauss syndrome in a few people taking zafirlukast or montelukast. Churg-Strauss syndrome is very rare, but it causes blood vessel inflammation in the lungs and can be life threatening. Oral steroids quickly resolve the problem. In fact, usually the syndrome has occurred in patients who were tapering off steroids and changing over to the leukotriene-antagonists. Some experts believe that, in such cases, the steroids may simply have masked the presence of the disorder, which then developed when the steroid drugs were withdrawn. Symptoms include severe sinusitis, flu-like symptoms, rash, and numbness in the hands and feet.

Other concerns are indications of liver injury in patients taking zileuton and zafirlukast when taken at higher than standard doses. No adverse effects on the liver have been reported to date with montelukast.

Theophylline (Theo-Dur, Theolair, Slo-Phyllin, Slo-bid, Constant-T, Respbid) is a mild-to-moderate bronchodilator that has been used to treat childhood asthma for more than 30 years. It is useful for treating nocturnal asthma and may also have anti-inflammatory qualities even in low doses.

Available in tablet, liquid, and injectable forms, some theophylline sustained-release tablets and capsules have a long duration of action and can therefore be taken once or twice a day with good results.

Side effects may include changes in behavior, mood, and memory. If theophylline is not taken exactly as prescribed, an overdose can easily occur. Toxicity can cause nausea, vomiting, headache, insomnia, and, in rare cases, disturbances in heart rhythm and convulsions. Contact a doctor immediately if any of these side effects occur.

The risks for these adverse effects are small if the drug is taken exactly as prescribed but the following precautions should be noted:

Infants tend to metabolize the drug extremely slowly and, therefore, should receive very low doses.
By the time children reach age 1, however, they metabolize the drug faster than adults. There is a risk, therefore, of toxic effects.
Fever and certain antibiotics may slow down the rate at which theophylline is eliminated from the body. In such cases, the doctor may want to reduce the dosage of theophylline.

If a child is taking theophylline on an ongoing basis, the doctor should monitor the drug level at the start of therapy and at regular intervals thereafter.

Omalizumab (Xolair) is FDA-approved for patients age 12 and older who have moderate-to-severe persistent asthma related to allergies. The first drug of this type to be approved for asthma, omalizumab is a monoclonal antibody (MAb), a genetically developed drug designed to attack very specific targets. Omalizumab is administered by injection every 2 - 4 weeks. It is used only to treat patients whose symptoms are not controlled by inhaled corticosteroids.

Omalizumab prevents the antibody immunoglobulin E (IgE) from triggering the inflammatory events that lead to asthmatic attacks. Studies have shown excellent benefits of the drug, including a reduced need for corticosteroids, fewer hospitalizations, and significant symptomatic improvements.

However, about 1 in 1,000 patients who take omalizumab develop anaphylaxis (a life-threatening allergic reaction). In 2007 the FDA requested the manufacturers of omalizumab to put a “boxed warning” on the medicine’s label emphasizing the drug’s risk for anaphylaxis. The boxed warning notes that patients can develop anaphylaxis after any dose of omalizumab, even if they had no reaction to a first dose. Anaphylaxis may occur up to 24 hours after the dose is given.

The FDA recommends that healthcare providers observe patients for at least 2 hours after an injection. Patients should also carry emergency self-treatment for anaphylaxis (such as an Epi-Pen) and know how to administer it. With an Epi-Pen, or similar auto-injector device, patients can quickly give themselves a life-saving dose of epinephrine.

Anaphylaxis symptoms include:

Difficulty breathing
Chest tightness
Dizziness
Fainting
Itching and hives
Swelling of the mouth and throat

[See In-Depth Report #4: Asthma in adults.]

Other Treatments

Alternative therapies are widely used by children, adolescents, and adults with asthma. In one study, nearly half of asthma or allergy sufferers resorted to alternative treatments. To date, however, evidence does not support most alternative therapies, including high-dose vitamins, urine injections, homeopathic remedies, and most herbal remedies.

Relaxation and Stress-Reduction Techniques. Patients report benefits from many stress reduction and physical techniques, such as acupuncture, hypnosis, breathing relaxation techniques, the Alexander technique, massage therapy, and meditation practices. There have been very few well-conducted studies supporting their use, however.

Acupuncture, hypnosis, and biofeedback are alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Breathing Exercises. Some studies have suggested that breathing exercises or training may be helpful. A number of different methods are available. One example is the Buteyko breathing method, an experimental approach designed to increase levels of carbon dioxide in the body. To do this, patients are trained to reduce their volume of breath and to avoid hyperventilation (over-breathing). Some studies report that patients using this method reduce their use of medications and improve their quality of life. The system originated in Australia and is not yet widely available in the U.S.

Probiotics. Probiotics are beneficial bacteria that may possibly help protect against allergies and asthma. Antibiotic overuse and modern hygiene may specifically be reducing these helpful organisms. Look for probiotics in active yogurt cultures and in supplements, which are being studied for protection.

Herbal Remedies. Butterbur (also known as Petasites hybridus, butter dock, blatterdock, bog rhubarb, and exwort), is a traditional herbal remedy used for seasonal allergies and asthma. In a 2002 study, it was as effective and less sedating than a commonly prescribed antihistamine for treating seasonal allergies over a 2-week period. However, little research exists on its effect on asthma. Overall, there is scant evidence supporting the benefits of herbs and nutritional supplements for asthma control.

Managing Asthma

The more allergies a child has, the more severe the asthma. Making lifestyle changes to reduce allergy attacks and other triggers is extremely important.

House dust is a reservoir for pollen and dust mites. Some experts believe that reducing household allergens and pollutants in the home could reduce asthma in children by 40%.

Controlling for Dust. Spray furniture polish is very effective for reducing both dust and allergens. Air cleaners, filters for air conditioners, and vacuum cleaners with High Efficiency Particular Air (HEPA) filters can help remove particles and small allergens found indoors. Neither vacuuming nor the use of anti-mite carpet shampoo, however, is effective in removing mites in house dust. Vacuuming actually stirs up both mites and cat allergens. If possible, avoid carpets and rugs.

Click the icon to see an image of a HEPA air filter.

Bedding and Curtains. Many experts recommend reducing exposure to dust mites by enclosing mattresses and pillows in semipermeable coverings. (Vinyl mattress covers limit airflow and may also worsen, or even cause, asthma in children. Synthetic pillows may pose a significantly higher risk for severe asthma attacks in children than feather or no pillows.) However, several 2005 studies suggested that such covers do not prevent asthma or allergies. Replace curtains with shades or blinds, and wash bedding using the highest temperature setting.

Click the icon to see an image of dust mite prevention.

One study found that children sleeping in bottom bunk beds are significantly more likely to develop asthma than siblings occupying the upper bunks. Families with children who have asthma or allergies should avoid bunk beds or be sure that children with asthma sleep in the top bunk. Even with standard beds, it may be useful to have them sleep as high off the floor as possible.

Exterminating Pests (Cockroaches and Mice). Use professional exterminators to eliminate cockroaches. (One study reported that ridding a home of cockroaches and cleaning the house using standard housecleaning techniques failed to eliminate the cockroach allergens themselves.) Exterminate mice, and attempt to remove all dust, which might contain mouse urine and dander.

Reducing Humidity in the House. Although warm, moist air from vaporizers can greatly ease and moderate asthma attacks, living in a damp house is counterproductive. Dust mites thrive in humidity and damp houses increase the risk for mold, so on-going humidifiers can be unhelpful. If they are used, humidity levels should not exceed 40%, and humidifier should be cleaned daily with a vinegar solution.

Controlling Pets. People with asthma who already have pets and are not allergic to them probably have a low risk for developing such allergies later on. When children are exposed to more than one dog or cat during their first year, they have a much lower risk for allergies and asthma.

For children who have an existing allergy to pets, however, the pets should be given away or kept outside. If this isn't possible, they should at least be confined to carpet-free areas outside the bedroom. Cats harbor significant allergens, which can even be carried on clothing; dogs usually present fewer problems. Washing animals once a week can reduce allergens. Dry shampoos, such as Allerpet, are now available for both cats and dogs to remove allergens from skin and fur and are easier to administer than wet shampoos.

Many of the same substances trigger both allergies and asthma. Common allergens include pollen, dust mites, mold and pet dander. Other asthma triggers include irritants like smoke, pollution, fumes, cleaning chemicals, and sprays. Asthma symptoms can be substantially reduced by avoiding exposure to known allergens and respiratory irritants.

Preventing Exposure to Cigarette and Cooking Smoke. Parents who smoke are strongly urged to quit. Studies indicate that exposure to second-hand smoke in the home increases the risk for asthma and asthma-related emergency room visits in children. Even smoky cooking can worsen asthma.

Parental smoking has been shown to increase the airway responsiveness of infants as early as the first 2 - 10 weeks of life. This extends even to the fetus of pregnant women who smoke. Such mothers tend to have babies born at a low birth weight, which affects lung function and increases babies' risks for asthma.

Avoiding Outdoor Allergens. The following are some recommendations for avoiding allergens outside:

Avoid scheduling camping and hiking trips during times of high pollen count (generally, May and June for grass pollen and mid-August to October for ragweed).
Patients should avoid strenuous activity when ozone levels are highest, which usually occur in early afternoon, particularly on hot hazy summer days. Levels are lowest in early morning and at dusk.
Asthma attacks are often higher during thunderstorms. Some evidence points to a build-up of ozone that accompanies such storms. Other evidence suggests that the changing airflow patterns bring a sudden downdraft of air containing concentrations of pollens, small particles and allergens.
Patients who are allergic to mold should avoid barns, hay, raking leaves, and mowing grass.
Exposure to automobile fumes may worsen asthma. Fungi in car air conditioners can also be a problem.

Reducing Exposure to Air Pollution. Children breathe faster than adults, taking in more pollutants, and therefore are particularly susceptible to soot and other small particles in the air. A 2001 study found an association between higher rates of asthma and other health problems in children who were exposed to high levels of specific pollutants (particularly sulfur dioxide and nitrogen dioxide). Diesel fuel exhaust has also been associated with worsening asthma in children.

Some experts point out that asthma rates in North America have increased over recent years while the prevalence of many common air pollutants have declined. So pollution is unlikely to be a primary cause of asthma. Regardless of whether pollution is an important cause of asthma, evidence strongly suggests that it can affect existing asthma.

Patients with asthma and chronic allergic rhinitis may require daily medications. Patients with severe seasonal allergies may be advised to start medications a few weeks before the pollen season, and to continue it until the season is over.

Immunotherapy ("allergy shots") may help reduce asthma symptoms, and the use of asthma medications, in patients with known allergies. They may also help prevent the development of asthma in children with allergies. Immunotherapy poses some risk for severe allergic reactions, especially for children with poorly controlled asthma, so it is important that the doctor carefully evaluates the child’s asthma condition.

[See In-Depth Report #77: Allergic rhinitis.]

Weight Loss. Children who are both asthmatic and overweight may reduce asthma symptoms simply with weight loss.

Fruits, Vegetables, and Whole Grains. Healthy foods are important for lung function. Specific foods that may be important for healthy lungs contain antioxidants (deep green and yellow-orange fruits and vegetables), selenium (fish, red meat, grains, eggs, chicken, liver, garlic), plant chemicals called flavonoids (apples, onions), and magnesium (green leafy vegetables, nuts, whole grains, milk, and meats).

Fish Oil. Omega-3 fatty acids, found in cold water oily fish and in supplements (preferably DHA-EPA, the important compounds in fish oil) have anti-inflammatory effects. Some evidence suggests they may be helpful for people with asthma.

Caffeine. Caffeine has properties that are similar to the asthma drug theophylline. A major analysis of studies reported that caffeine improved lung function for up to 4 hours after consumption. Although tea and coffee are the major sources of caffeine, some sodas contain it and should be avoided when children have an asthma attack. (People who are going to have their lung function tested should avoid drinking coffee, tea, or other caffeinated beverages for at least 4 hours beforehand.)

Food Allergies. Although about 70% of people with asthma believe their symptoms are aggravated by food allergies, studies indicate that this belief may be true in only 5% of cases. If young children show signs of or test positive for food allergies, however, parents should be extra cautious in preventing exposure to any asthma trigger. Some doctors now counsel all children with asthma to avoid nuts entirely, and, of course, children who experience reactions to any foods should avoid them.

Chemicals that may pose some risk for an allergic reaction are monosodium glutamate, or MSG (found in some canned soups, cheese, and certain vegetables), and sulfites (preservatives in foods, such as frozen potatoes and tuna). Contrary to what many believe, dairy products do not appear to worsen asthma symptoms in people who are not already allergic to them.

Asthma is no reason to avoid exercise. Historically, about 10% of Olympic athletes have asthma. Some studies indicate that long-term exercise may help control asthma and reduce hospitalization.

Encourage children with asthma to swim and play sports, such as baseball, that will present less difficulty for them. Intense activities lasting less than 2 minutes, such as sprinting or competitive swimming, may cause fewer problems than longer-lasting exercises.

Young people who enjoy running should probably choose an indoor track to avoid pollutants. Swimming is excellent for people with asthma. Yoga practice, which uses both stretching, breathing, and meditation techniques, may have particular benefits. One study reported that two-thirds of patients who practiced yoga regularly were able to reduce or stop taking their asthma medications.

Patients should consult their doctors before starting any exercise program. Exercise-induced asthma is a limited condition that has specific recommendations.

People with asthma should try to minimize their risk for respiratory tract infections. Washing hands is a very simple but effective preventive measure.

Patients with asthma should ask their doctor about getting the influenza ("flu") vaccine and also whether they should receive the vaccination against pneumococcal pneumonia.

Zanamivir, a new drug used for treating influenza, is considered safe for patients with asthma 12 years of age or older. In one study, patients with asthma treated with zanamivir experienced fewer flu symptoms, and their lung function improved.

People with asthma have no higher rate of anxiety or depression than the general population. However, such emotions interact with the effects of asthma and its treatments in important ways:

Negative emotions can discourage compliance with medication and the ability to cope.
Poor control of asthma symptoms, in turn, increases the risk for negative emotions.
Stress and depression have been associated with more severe symptoms and even an increased risk of fatal asthma attacks.

Some evidence suggests that stress reduction techniques, a positive attitude, and relaxation techniques may be very helpful in the long-term management of asthma.

Resources

www.lungusa.org -- The American Lung Association
www.acaai.org -- American College of Allergy, Asthma & Immunology
www.aaaai.org -- American Academy of Allergy, Asthma, and Immunology
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.asthma-carenet.org -- Childhood Asthma Research and Education Network
www.njc.org -- National Jewish Center for Immunology and Respiratory Medicine
www.aafa.org -- Asthma and Allergy Foundation of America
www.aanma.org -- Allergy and Asthma Network, Mothers of Asthmatics

References

Akinbami L; Centers for Disease Control and Prevention National Center forHealth Statistics. The state of childhood asthma, United States, 1980-2005. Adv Data. 2006 Dec 12;(381):1-24.

Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med. 2006 May 11;354(19):1998-2005.

Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000052.

Douwes J, van Strien R, Doekes G, Smit J, Kerkhof M, Gerritsen J, et al. Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study. J Allergy Clin Immunol. 2006 May;117(5):1067-73.

Guilbert TW, Morgan WJ, Zeiger RS, Mauger DT, Boehmer SJ, Szefler SJ, et al. Long-term inhaled corticosteroids in preschool children at high risk for asthma. N Engl J Med. 2006 May 11;354(19):1985-97.

Haland G, Carlsen KC, Sandvik L, Devulapalli CS, Munthe-Kaas MC, Pettersen M, et al. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006 Oct 19;355(16):1682-9.

Marks GB, Mihrshahi S, Kemp AS, Tovey ER, Webb K, Almqvist C, et al. Prevention of asthma during the first 5 years of life: a randomized controlled trial. J Allergy Clin Immunol. 2006 Jul;118(1):53-61.

National Asthma Education and Prevention Program Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics -- 2002. Rockville, MD. National Heart, Lung, and Blood Institute, US Dept of Health and Human Services; 2003. NIH publications 02-5074.

O'Byrne PM, Pedersen S, Busse WW, Tan WC, Chen YZ, Ohlsson SV, et al. Effects of early intervention with inhaled budesonide on lung function in newly diagnosed asthma. Chest. 2006 Jun;129(6):1478-85.

Salpeter SR, Buckley NS, Ormiston TM, Salpeter EE. Meta-analysis: effect of long-acting beta-agonists on severe asthma exacerbations and asthma-related deaths. Ann Intern Med. 2006 Jun 20;144(12):904-12.

Schuh S, Dick PT, Stephens D, Hartley M, Khaikin S, Rodrigues L, Coates AL. High-dose inhaled fluticasone does not replace oral prednisolone in children with mild to moderate acute asthma. Pediatrics. 2006 Aug;118(2):644-50.

Sorkness CA, Lemanske RF Jr, Mauger DT, Boehmer SJ, Chinchilli VM, Martinez FD, et al. Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: the Pediatric Asthma Controller Trial. J Allergy Clin Immunol. 2007 Jan;119(1):64-72.

Review Date:
3/26/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Fibromyalgia

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Diagnosis
Conditions with Similar Sym...
Prognosis
Treatment
Lifestyle Changes
Behavioral Therapy
Medications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Causes

People with fibromyalgia have decreased activity in opioid receptors in parts of the brain that affect mood and the emotional aspect of pain, researchers have found. This might explain why fibromyalgia patients are likely to experience depression, and are not very responsive to opioid painkillers.
Researchers have identified a conflict between sensory perception and nervous system processing in people with fibromyalgia. One study suggests that people with the condition might have greater awareness of, or less tolerance for, movement problems (such as tremor) that don't match with their expected sensory feedback. This mismatch in sensory signals might enhance the perception of pain.

Treatment

New research adds to the evidence that exercise relieves some of the symptoms of fibromyalgia. Women with fibromyalgia who took part in a program that combined aerobic, strength training, and flexibility exercises had better physical and emotional function, as well as reduced symptoms. Another study found that an at-home exercise program improved upper body pain and function, especially in women who were having functional difficulties at the beginning of the study.
An anti-convulsant medication, gabapentin (Neurontin), significantly improved pain in fibromyalgia patients compared to placebo. Patients who took gabapentin also reported that they slept better and felt less tired.
The selective serotonin-reuptake inhibitor paroxetine (Paxil) significantly lowered patient scores on a fibromyalgia symptom questionnaire, and was well-tolerated, although the drug do much for their pain.

Introduction

Fibromyalgia is a syndrome of unknown causes that results in lasting, sometimes debilitating, muscle pain and fatigue. Fibromyalgia is also known as fibrositis or fibromyositis.

Pain. The primary symptom of fibromyalgia is pain. The pain can be in one place or all over. The exact locations of the pain are called tender points. The pain of fibromyalgia is often is described as follows:

Tender point pain occurs in local sites, usually in the neck and shoulders. The pain then spreads out from these areas. The actual pain starts at the muscles. The joints are not affected. There are no lumps or nodes associated with these points of pain, and no signs of inflammation (swelling). People diagnosed with fibromyalgia feel pain in at least 11 of 18 specific tender points.
Widespread pain described as stiffness, burning, and aching. The pain also "radiates," or spreads, to nearby areas. Most patients report feeling some pain all the time. Many describe it as "exhausting." The pain can vary depending on the time of day, weather changes, physical activity, and the presence of stressful situations. The pain is often more intense after disturbed sleep.

Fatigue and Sleep Disturbances. Another major complaint is fatigue. Some patients report that fatigue is more unbearable than their pain. Sleep disturbances, particularly restless legs syndrome, are also very common. Fatigue and sleep disturbances are almost universal in patients with fibromyalgia. Some experts believe that if these symptoms are not present, doctors should seek a diagnosis other than fibromyalgia.

Depression and Mood. Up to a third of patients have depression. Disturbances in mood and concentration are also very common. These conditions often go undiagnosed in patients with fibromyalgia.

Other Symptoms. The following symptoms may also be present:

Digestive problems, including irritable bowel syndrome with gas, and alternating diarrhea and constipation
Dizziness
Painful menstrual periods
Tension or migraine headaches
Tingling or numbness in the hands and feet
Urinary frequency caused by bladder spasms

Symptoms in Children. In general, children with fibromyalgia most often have sleep disorders and widespread pain.

Causes

The most common type is primary fibromyalgia, in which the causes are not known. Many experts believe that fibromyalgia is not a disease, but rather a chronic pain condition brought on by several abnormal body responses to stress. Physical injuries, emotional trauma, or viral infections such as Epstein-Barr may be triggers of the disorder, but none have proven to be a cause of primary fibromyalgia.

Research published in the December 2006 issue of Current Pain and Headache Reports found that the areas in the brain that are responsible for the sensation of pain are different in fibromyalgia patients from the same areas in healthy people.

People with fibromyalgia have been found to have decreased activity in opioid receptors in parts of the brain that affect mood and the emotional aspect of pain. This reduced response might explain why fibromyalgia patients are likely to havedepression, and are less responsive to opioid painkillers, researchers say.

Sleep disturbances are common in fibromyalgia. Both adult and young patients with fibromyalgia have a higher-than-average rate of a sleep disorder called periodic limb movement disorder (PLMD). PLMD used to be called nocturnal myoclonus. Patients with PLMD involuntarily contract their leg muscles every 20 - 40 seconds during sleep. This may occasionally wake up the patient.

Some researchers believe that fibromyalgia does not lead to poor sleeping patterns, but that sleep disturbances come first. Researchers continue to investigate the link between fibromyalgia and sleep.

In one study, healthy volunteers reported fibromyalgia-like pain after they had been subjected to disrupted deep sleep. Disturbed sleep appears to trigger factors in the immune system that cause inflammation, pain, fatigue, and lower tolerance to pain. A 2004 study found that patients with fibromyalgia have increased rates of cyclic alternating sleep pattern (CAP). Increased CAP produced serious sleep problems, which were strongly linked to symptom severity. Previous studies have also suggested that CAP may be related to PLMD.
A 2004 report found that sleep disorders that cause breathing problems are common in women with fibromyalgia.
Other biological measures of troubled sleep, however, such as levels of the hormone melatonin, which helps regulate circadian rhythms and the sleep-wake cycle, appear to be normal in most people with fibromyalgia.

Many abnormalities of hormonal, metabolic, and brain chemical activity have been described in studies of fibromyalgia patients. Changes appear to occur in several brain chemicals, although no regular pattern has emerged that fits most patients. Since there has been no clear cause-and-effect relationship established, this may be a result of the effects of pain and stress on the central nervous system, and not a cause of fibromyalgia.

Serotonin. Of particular interest to researchers is serotonin, an important nervous system chemical messenger found in the brain, gut, and other areas of the body. Serotonin plays important roles in feelings of well-being, adjusting pain levels, and promoting deep sleep. Serotonin abnormalities have been linked to many disorders, including depression, migraines, and irritable bowel syndrome. Lower serotonin levels have also been noted in some patients with fibromyalgia.

Stress Hormones. Researchers have also found abnormalities in the hormone system known as the hypothalamus-pituitary-adrenal gland (HAP) axis. The HAP axis controls important functions, including sleep, response to stress, and depression. Changes in the HAP axis appear to produce lower levels of the stress hormones norepinephrine and cortisol. (By contrast, levels of stress hormones in depression are higher than normal.) Deficiencies in the levels of stress hormones produce impaired and weaker responses to psychological or physical stresses. (Examples of physical stress include infection or exercise.)

The hypothalamus is a highly complex structure in the brain that regulates many important brain chemicals.

Click the icon to see an image of the adrenal glands.

Low Growth Hormone Levels. Some studies have reported low levels of insulin-like growth factor-1 (IGF-1) in about a third of fibromyalgia patients. IGF-1 is a hormone that is controlled by the adult growth hormone, and promotes bone and muscle growth. Low levels of growth hormone are related to impaired thinking, lack of energy, muscle weakness, and intolerance to cold. Studies suggest that changes in growth hormone likely stem from the hypothalamus in the brain. While researchers did not find a link between IGF-1 levels and fibromyalgia, a 2005 study indicated that serum growth hormone levels may be a marker of the disorder.

Abnormal Pain Perception and Substance P. Some studies have suggested that fibromyalgia may involve too much activity in the parts of the central nervous system that process pain (the nociceptive system). Brain scans of fibromyalgia patients have suggested abnormalities in pain processing centers. For example, researchers have detected up to three times the normal level of substance P in the cerebrospinal fluid of fibromyalgia patients. Substance P, a chemical messenger of the nervous system, is associated with increased pain perception.

Some fibromyalgia patients may also be oversensitive to external stimulation, and overly anxious about the sensation of pain. This increase in awareness is called generalized hypervigilance. One study compared patients with fibromyalgia or rheumatoid arthritis to those without chronic pain. Researchers then measured the different groups' responses to pain and noise. Of the three groups, the fibromyalgia patients were least tolerant, and most aware, of such stimuli. However, one analysis of studies on fibromyalgia found no strong support for the hypervigilance theory.

A conflict between sensory perception and nervous system processing might occur in people with fibromyalgia. Fibromyalgia patients have been found to have greater awareness of, or less tolerance for, movement problems (such as tremor) that don't match with their expected sensory feedback. This mismatch in sensory signals might enhance the perception of pain.

Fibromyalgia has symptoms that resemble those of some rheumatic illnesses, including rheumatoid arthritis and lupus (systemic lupus erythematosus). These are autoimmune diseases in which a defective immune system mistakenly attacks the body's own healthy tissue, producing inflammation and damage. The pain in fibromyalgia, however, does not appear to be due to autoimmune factors, and there is little evidence to support a role for an inflammatory response in fibromyalgia.

Although not primary causes, psychological and social factors may contribute to fibromyalgia in three ways:

They could make individuals susceptible to fibromyalgia.
They may play some role in triggering the onset of the condition.
They may perpetuate, or be responsible for, the condition.

Studies have reported a greater number of severe experiences of emotional and physical abuse in patients with fibromyalgia, compared with the general population. Most often, the abuse came from family members or partners. This suggests that post-traumatic stress disorder (PTSD) or chronic stress may play a strong role in the development of fibromyalgia in some patients. PTSD, an anxiety disorder, is a reaction to a specific traumatic event. Symptoms of this condition, which can last for years after the traumatic event, include emotional withdrawal, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle response to noise. Some evidence indicates that PTSD actually results in changes in the brain, possibly from long-term over-exposure to stress hormones.

Some research found muscle abnormalities in fibromyalgia patients. These problems can be classified as the following:

Biochemical abnormalities: For example, one study reported that fibromyalgia patients had lower levels of the muscle-cell chemicals phosphocreatine and adenosine triphosphate (ATP). Such chemicals regulate the level of calcium in muscle cells. Calcium is an important component in the muscles' ability to contract and relax. If ATP levels are low, calcium is not "pushed back" into the cells, and the muscle remains contracted.
Functional abnormalities: The pain and stress of the disease itself may harm muscle function.
Structural and blood flow abnormalities: Some researchers saw overly thickened capillaries (tiny blood vessels) in the muscles of fibromyalgia patients. The abnormal capillaries could produce lower levels of compounds essential for muscle function, as well as reduce the flow of oxygen-rich blood to the muscles.

To date, none of these abnormalities have a clearly defined relationship with fibromyalgia.

Risk Factors

About 3.7 million Americans have fibromyalgia. The condition affects 2% of Americans, including 3.4% of women and 0.5% of men.

Some evidence suggests that several factors may make people more susceptible to fibromyalgia. These risk factors include:

Being female
Coming from a very stressful culture or environment
Having a psychological vulnerability to stress
Having had difficult experiences in childhood

Nine out of 10 fibromyalgia patients are women. Women may be more prone to develop fibromyalgia during menopause.

The disorder usually occurs in people ages 20 - 60 years, though it can occur at any time. Some studies have noted peaks around age 35. Others note that fibromyalgia is most common in middle-aged women. In one study, cases of fibromyalgia increased with age, and reached a frequency of more than 7% among people in their 60s and 70s.

Juvenile Primary Fibromyalgia. This type of fibromyalgia appears in adolescents, typically after age 13, with a peak incidence at age 14. It is uncommon, but studies indicate that its incidence may be increasing. One study found that 1.2% of school children, all girls, met the criteria for fibromyalgia. Other studies have found an even higher frequency of fibromyalgia in children. Symptoms are similar to adult fibromyalgia, but outcomes may be better in young people.

Studies report a higher incidence of fibromyalgia among family members. It is not clear if genetic or psychological factors, or both, are involved.

One study reported that 28% of the children of mothers with fibromyalgia also develop the disorder. Offspring who developed fibromyalgia were no more likely to have psychological disorders than those who did not.
Another study noted that 66% of parents of children with fibromyalgia reported some sort of chronic pain. About 10% of them had fibromyalgia.

Diagnosis

There is no obvious, objective method for diagnosing fibromyalgia. The criteria used for studying fibromyalgia are very helpful, particularly if the patient does not have any accompanying disorder, such as depression or arthritis, which could complicate the diagnosis. Failure to meet the criteria, however, does not rule out fibromyalgia. Fibromyalgia should be suspected in any person with muscle and joint pain with no identifiable cause.

In 1990, the American College of Rheumatology (ACR) set the following criteria for the classification of fibromyalgia:

A. Widespread pain must be present for at least 3 months. This pain must appear in all of the following locations:

Both sides of the body
Above and below the waist
Along the length of the spine

B. Pain in at least 11 of 18 specific areas called tender points on the body. The pain experienced when pressing on a tender point is very localized and intensely painful (not just tender). Tender points are located in the following areas:

The left or right side of the back of the neck, directly below the hairline
The left or right side of the front of the neck, above the collar bone (clavicle)
The left or right side of the chest, right below the collar bone
The left or right side of the upper back, near where the neck and shoulder join
The left or right side of the spine in the upper back between the shoulder blades (scapula)
The inside of either arm, where it bends at the elbow
The left or right side of the lower back, right below the waist
Either side of the buttocks below the hip bones
Either kneecap

Other Factors. The ACR classification provides a guideline, but doctors will also use a patient's medical history and other symptoms to reach a diagnosis. Fibromyalgia is often diagnosed when other diseases have been excluded. Long-term symptoms that may indicate fibromyalgia include:

Fatigue
Headache
Morning stiffness
Numbness or tingling in the hands and feet
Sleep disturbance

The 18 fibromyalgia tender points are located throughout the body. According to the American College of Rheumatology, a diagnosis of fibromyalgia requires widespread body pain plus localized pain in 11 of these 18 specific points.

A doctor should always take a careful personal and family medical history, which would include a psychological profile and a history of any factors that might indicate disorders other than fibromyalgia. Such factors might include:

Infectious diseases
Muscle weakness
Physical injuries
Rashes
Recent weight change
Sexual, physical, or substance or alcohol abuse

Patients should report any drugs they take, including vitamins and over-the-counter or herbal medications.

Pressure on Tender Spots. Any physical examination for fibromyalgia requires that the doctor press firmly on all potential tender spots. They must be painful when pressed, not simply tender. In addition, for a doctor to reach a diagnosis of fibromyalgia, these tender sites should normally not show signs of inflammation (redness, swelling, or heat in the joints and soft tissue). The tender points may also change in location and sensitivity over time. A doctor, then, may recheck tender points that do not respond the first time, in patients who have other significant symptoms.

Detection of Other Causes of Symptoms. A health care provider will also examine nails, skin, mucous membranes, joints, spine, muscles, and bones to help rule out arthritis, thyroid disease, and other disorders.

No blood, urine, or other laboratory tests can provide a definitive diagnosis of fibromyalgia. If such tests show abnormal results, the doctor should look for other disorders. Tests for specific diseases depend on family histories and other symptoms. They may include:

Blood count
Sedimentation rate
Tests of certain antibodies
Thyroid and liver function tests

The doctor may suggest follow-up psychological profile testing, if laboratory results do not indicate a specific disease.

Conditions with Similar Symptoms

Between 10 - 30% of all doctor office visits are due to symptoms that resemble those of fibromyalgia, including fatigue, malaise, and widespread muscle pain. Since no laboratory test can confirm a diagnosis of fibromyalgia, doctors will usually first test for similar conditions. It should be noted that a diagnosis of many of the disorders below may not always rule out fibromyalgia, since it can accompany other common and similar conditions.

Several conditions overlap or often coexist with fibromyalgia, and have similar symptoms. It is not clear if these conditions cause fibromyalgia, are risk factors for the disorder, have causes in common with fibromyalgia, or have no relationship at all with it.

Chronic Fatigue Syndrome. There is a significant overlap between fibromyalgia and chronic fatigue syndrome (CFS). In a 2003 study, for example, 43% of CFS patients also had a diagnosis of fibromyalgia. As with fibromyalgia, the cause of CFS is unknown. A doctor can diagnose either disorder based only on symptoms reported by the patient. The two disorders share most of the same symptoms. They are also treated almost identically. The differences are primarily the following:

Pain with tender points is the primary symptom in fibromyalgia. Some patients with CFS exhibit similar tender pressure points. However, muscle pain is less prominent in patients with CFS.
Fatigue is the dominant symptom in CFS. It is severe and not relieved by rest or sleep, and it is not the result of excessive work or exercise.

Some doctors believe that fibromyalgia is simply an extreme type of chronic fatigue syndrome. There Some physical evidence, however, indicates that the two disorders are distinct, with treatments that are specific to each.

Myofascial Pain Syndrome. Myofascial pain syndrome can be confused with fibromyalgia and may also accompany it. Unlike fibromyalgia, myofascial pain tends to occur in trigger points, as opposed to tender points, and typically there is no widespread, generalized pain. Trigger-point pain occurs in tight muscles, and when the doctor presses on these points, the patient may experience a muscle twitch. Unlike tender points, trigger points are often small lumps, about the size of a pencil eraser.

Major Depression. The link between psychological disorders and fibromyalgia is very strong and problematic. Certain studies report that 50 - 70% of fibromyalgia patients have a lifetime history of depression. Only 18 - 36% of fibromyalgia patients, however, also have major depression, a severe form of depression.

Some studies found that people who have both psychological disorders and fibromyalgia are more likely to seek medical help, compared with patients who simply have symptoms of fibromyalgia. If this is the case, study results may be biased, favoring a higher-than-actual association between depression and fibromyalgia.

Depression most likely does not cause fibromyalgia, but it may increase susceptibility. Depressed feelings in people with fibromyalgia can certainly be normal responses to the pain and fatigue caused by this syndrome. Such emotions, however, are temporary and related to the situation a person is in. They are not considered to be a depression disorder. Unlike ordinary periods of sadness, an episode of major depression disorder can last many months.

Symptoms of major depression include the following:

Depressed mood every day
Feeling worthless or inappropriately guilty
Inability to concentrate or make decisions
Insomnia or excessive sleeping
Low energy every day
Restlessness or a sense of being slowed down
Significant weight gain or loss (of 10% or more of an individual's typical body weight)
Suicidal thoughts

If several of the above symptoms are present, and none of the physical symptoms (particularly the tender points) of fibromyalgia exist, the condition is most likely major depression.

Chronic Headache. Chronic primary headaches such as migraines are common in fibromyalgia patients. Some experts believe that migraine headaches and fibromyalgia may even share common defects in the systems that regulate certain chemical messengers in the brain, including serotonin and epinephrine (adrenaline). Low levels of magnesium have also been noted in patients with both fibromyalgia and migraines. In fact, chronic migraine sufferers who fail to benefit from usual therapies may also have fibromyalgia.

Symptoms of a migraine attack may include heightened sensitivity to light and sound, nausea, vision problems (auras), speech difficulty, and intense pain predominating on one side of the head.

Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a term that describes conditions in which certain chemicals can cause symptoms similar to CFS or fibromyalgia in some people. Still, as with CFS and fibromyalgia, some experts are uncertain whether MCS is a medical condition or if it is psychologically based.

In one study, for example, CFS patients who believed their problem was chemically triggered were exposed to either an active chemical or a placebo (an inactive substance). Both groups reported symptoms, including those only exposed to a placebo. Because everyone is exposed to many chemicals on a daily basis, it is very difficult to determine whether chemicals are responsible for specific symptoms.

Experts have come up with criteria to help recognize MCS:

Symptoms can be produced by exposure to the chemical at levels lower than previously or usually tolerated.
Symptoms can be triggered by multiple substances that are chemically unrelated.
Symptoms involve multiple organ systems.
The condition is chronic.
The symptoms always happen with repeated exposure to a chemical. (These are often common chemicals found in popular products, such as perfumes, fabric softeners, and air fresheners.)
The symptoms improve when the chemical is removed.

Restless Legs Syndrome. About 15% of people with fibromyalgia have restless legs syndrome. Restless legs syndrome is an unsettling and poorly understood movement disorder that is sometimes described as a sense of unease and weariness in the lower leg that is aggravated by rest and relieved by movement.

Disorders Affected by the Sympathetic (also called Autonomic) Nervous System. Other conditions that commonly accompany fibromyalgia include:

Chest pain and heart palpitations
Mitral valve prolapse
Sudden drop in blood pressure

Certain stress-related disorders commonly occur with fibromyalgia, and have overlapping symptoms. In fact, some experts believe these disorders so often interact that they may all be part of one general condition.

Chemicals and environmental toxins -- exposure to various chemicals and environmental toxins such as solvents, pesticides, or heavy metals (cadmium, mercury, or lead) can cause fatigue, chronic pain, and other symptoms of fibromyalgia.
Irritable bowel syndrome
Osteoarthritis -- a common form of arthritis than can coexist with fibromyalgia. The two conditions may be confused, particularly in elderly people. Osteoarthritis, however, causes joint pain, not widespread or generalized pain.

Osteoarthritis is a chronic disease of the joint cartilage and bone. It is often thought to result from "wear and tear" on a joint, although there are other causes, such as congenital defects, trauma, and metabolic disorders. Joints appear larger, are stiff and painful, and usually feel worse the more they are used throughout the day.

Temporomandibular joint disorders

Some tests may be positive for one or more of these diseases. However, if the results are uncertain or weak, or if these conditions have been treated successfully, fibromyalgia should not be ruled out if the patient still meets the criteria for it.

Multiple sclerosis. This condition may have symptoms similar to those of fibromyalgia. Magnetic resonance imaging (MRI) scans often detect patches of tissue in the brain that confirm the presence of multiple sclerosis (MS). MRI findings combined with other tests and clinical findings usually make this diagnosis fairly certain. However, some patients may have symptoms that suggest MS, but diagnostic tests cannot confirm the diagnosis. Some of these patients may have symptoms similar to those of fibromyalgia.

Click the icon to see an image of multiple sclerosis.

Sjogren syndrome. This condition, characterized by dry eyes and mouth, is sometimes mistaken for fibromyalgia.

Autoimmune diseases. Rheumatoid arthritis, systemic lupus erythrometosis, and Sjogren syndrome are usually easy to diagnose but may develop slowly and be difficult to diagnose at first. Even if a doctor determines that a patient is most likely to have fibromyalgia, the doctor should keep track of any changes in symptoms over time in case one of these other illnesses is actually present.

Lyme Disease. Lyme disease is a bacterial disease transmitted by ticks. Health care providers can usually diagnose early Lyme disease correctly, but a delayed response or recurrence of this disorder may be mistaken for fibromyalgia. Some experts believe that 15 - 50% of patients referred to clinics for Lyme disease actually have fibromyalgia. Late Lyme disease can usually (but not always) be ruled out using blood tests that identify the organism that causes this disease. If fibromyalgia patients are incorrectly diagnosed and treated for Lyme disease with prolonged courses of antibiotics, the drugs may have serious side effects.

Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, symptoms of dependency on, or abuse of, alcohol or drugs appear as constant fatigue. Health care providers should consider medications as a possible cause of fatigue if an individual has recently started, stopped, or changed medications. Withdrawal from caffeine can produce depression, fatigue, and headache.

Polymyalgia Rheumatica. Polymyalgia rheumatica is a condition that causes pain and stiffness, and generally occurs in older women. Tender points are also present with this disorder, although they almost always occur in the hip and shoulder area. Morning stiffness is common, and patients may also experience fever, weight loss, and fatigue. A higher-than-normal erythrocyte sedimentation rate (ESR) can suggest polymyalgia rheumatica. Elevated ESR, however, also occurs with other conditions. Polymyalgia rheumatica often gets better in about a year, but there is a risk of persistent disease. Worse, it is sometimes associated with a rare condition called temporal arteritis, which may cause blindness if not treated, so an accurate diagnosis of polymyalgia rheumatica is important.

Prognosis

Fibromyalgia can be mild or disabling, and the emotional toll can be substantial. About half of all patients have difficulty with routine daily activities, or are unable to perform them. An estimated 30 - 40% of patients have had to quit work or change jobs. In a 2003 study, patients with either CFS or fibromyalgia were more likely to suffer losses of jobs, possessions, and support from friends and family than were people suffering from other conditions that caused fatigue.

The pain, emotional consequences, or sleep disturbances that come with fibromyalgia may lead to self-medication and overuse of sleeping pills, alcohol, drugs, or caffeine.

Outlook in Adults. Some studies show that fibromyalgia symptoms remain stable over the long term, while others report a better outlook, with 25 - 35% of patients reporting improvement in pain symptoms over time. Studies suggest that regular exercise specifically improves the outlook. Those with a significant life crisis, or who were on disability, had a poorer outcome than others. Outcome was determined by improvements in the patients' ability to work, their own feelings about their condition, pain sensation, and levels of disturbed sleep, fatigue, and depression. Although the disease is life-long, it does not get worse and is not fatal.

Outlook in Children. Children with fibromyalgia tend to have a better outlook than adults with the disorder. Several studies reported that more than half of children with fibromyalgia recover in 2 - 3 years.

Treatment

Many patients with fibromyalgia are treated first with medication; however, the American Pain Society Fibromyalgia Panel recommends a combined approach using cognitive-behavioral therapy, education, medication, and exercise.

Fibromyalgia is a mysterious condition. Its causes are still largely unknown, as is how it inflicts damage. No strong evidence indicates that any single treatment (or combination of treatments) has any significant effect for most patients. However, in 2007 the U.S. Food and Drug Administration approved pregabalin (Lyrica) as the first drug treatment for fibromyalgia after a study showed the medicine reduced fibromyalgia pain by at least 50% in 63% of patients.

Treatment usually involves not only relieving symptoms but also changing a pateint's attitude about their disease. Treatment should also teach patients behaviors that help them cope.

Treatments usually involve trial and error:

Patients may start with physical therapy, exercise, stress reduction techniques, and cognitive-behavioral therapy.
If these methods fail to improve symptoms, an antidepressant or muscle relaxant may be added to the treatment. Doctors usually prescribe these drugs because they can may improve pain tolerance.
Patient education and programs that encourage coping skills are an important part of any treatment plan.

According to a 2005 study published in the Clinical Journal of Pain, a combination of non-drug therapies works just as well as drug therapy in improving pain, depression, and disability. This combination includes exercise, stress management, massage, and diet.

Patients must have realistic expectations about the long-term outlook of their condition, and their own individual abilities. It is important to understand that fibromyalgia can be managed, and patients can live a full life. The following tips may be helpful when starting a treatment program for fibromyalgia:

The goal of therapy is to relieve symptoms, not cure them.
Treatment must be tailored to each patient, and a combination approach is often needed.
Patients must begin all treatments with the attitude that these treatments are trial-and-error. There is no clear treatment solution. Patients and doctors need to work together to make the best choices for individual symptoms and concerns.
Treatments are long-lasting, in some cases life-long, and patients should not be discouraged by the return of symptoms (relapses).
Enlisting family members, partners, and close friends, particularly to help with exercise and stretching programs, can be helpful.
Becoming involved with support groups of fellow patients also benefits many patients. Support groups may also benefit family members, particularly parents of children with fibromyalgia. One study noted that the severity of the disorder increased in children whose parents were less able to cope with their child's pain.

The definition of improvement is personal. For example, some patients are pleased with only a 10% reduction in pain and other symptoms.

Lifestyle Changes

Many studies have shown that exercise is the most effective component in managing fibromyalgia, and patients must expect to take part in a long-term exercise program. Physical activity prevents muscle wasting, increases well-being, and, over time, reduces fatigue and pain. Many studies have also demonstrated the exercise can improve physical and emotional function, as well as reduce symptoms, including pain.

Programs often combine aerobic, strength-training, and flexibility exercises with self-management education. Some studies have shown improvements lasting for up to 9 months after the exercise program.

Graded Exercise. The basic approach used for fibromyalgia is called graded exercise. Graded exercise means you slowly increase the amount of your physical activity.

In general, graded exercise involves:

A very gradual program of activity, beginning with mild exercise and building in intensity over time.
Stretching exercises before exercising. A daily stretching routine can help relax tense muscles and prevent muscle soreness.
Walking, swimming, and using equipment such as treadmills or stationary bikes. Swimming and water therapy are good because they don't require putting weight on the joints.

Patients who try hard exercises too early actually experience an increase in pain, and are likely to become discouraged and quit.

Every patient must be prepared for relapses and setbacks, but should not get discouraged. Patients who do not respond to one type of exercise might consider experimenting with another form.

Physical therapy can be very helpful. Studies suggest that physical therapy may reduce muscle overload, lessen fatigue from poor posture and positioning, and help condition weak muscles.

Sleep is essential, particularly since sleep disruptions worsen pain. Many patients with fibromyalgia have trouble getting a restful and healing night's sleep. Those who are unable to sleep consistently have low improvement. Swing shift work, for example, is extremely hard on fibromyalgia patients. Poor sleep habits can add to sleep problems. Tips for good sleep habits include:

Avoid caffeine or alcohol 4 - 6 hours before bedtime.
Avoid drinking fluids right before bedtime so that needing to uriniate does not disturb your sleep.
Avoid exercising 6 hours before bedtime.
Avoid large meals before bedtime. A light snack, however, may help you sleep.
Avoid naps, especially in the evening or late afternoon.
Establish a regular time for going to bed and getting up in the morning. Maintain this schedule even on weekends and during vacation.
If you are unable to fall asleep after 15 or 20 minutes, go into another room and start a quiet activity. Return to bed when you feel sleepy.
Minimize light and maintain a comfortable, moderate temperature in the bedroom. Keep the bedroom well ventilated.
Use the bed only for sleep and sexual relations.

[For more information see In-Depth Report #27: Insomnia.]

Fibromyalgia patients should maintain a healthy diet low in animal fat and high in fiber, with plenty of whole grains, fresh fruits, and vegetables. Although everyone should be careful about calories from fats, some are healthy.

Omega-3 Fatty Acids. Oils containing omega-3 fatty acids are of particular interest for arthritic pain. Such oils are found in cold-water fish. You can also purchase these oils as supplements called EPA-DHA or omega 3.

Omega-3 fatty acids are a form of polyunsaturated fat that the body gets from food. Omega-3s are known as essential fatty acids (EFAs) because they are important for good health. These healthy fatty acids can be found in certain fish, dark green leafy vegetables, and some oils. Omega-3 fatty acids have anti-inflammatory properties, which help prevent blood clots, lower cholesterol and triglyceride levels, and reduce blood pressure. Omega-3s may also reduce the risks and symptoms of diabetes, stroke, rheumatoid arthritis, asthma, inflammatory bowel disease, ulcerative colitis, some cancers, and mental decline.

Vegetarian Diet. A vegan diet has no meat, dairy, or eggs and includes uncooked fruits, vegetables, nuts, and germinated seeds. The actual benefit of various vegetarian diets remains unproven.

Relaxation and stress-reduction techniques are proving to be helpful in managing chronic pain. Evidence shows that people with fibromyalgia have a more stressful response to daily conflicts and encounters than those without the disorder. Several relaxation and stress-reduction techniques may be helpful in managing chronic pain:

Biofeedback
Deep breathing exercises
Hypnosis
Massage therapy
Meditation
Muscle relaxation techniques

Biofeedback. Evidence from controlled trials does not suggest that biofeedback techniques may be very helpful for fibromyalgia patients. During a biofeedback session, electric leads are taped to a subject's head. The person is encouraged to relax using any method that works. Brain waves are measured and an audio signal sounds when alpha waves are detected. Alpha waves are brain waves that occur with a state of deep relaxation. By repeating the process, people using biofeedback connect the sound with the relaxed state, and learn to achieve relaxation on their own.

Meditation. Meditation, used for many years in Eastern cultures, is now widely accepted in this country as an effective relaxation technique. A number of studies are reporting its benefits for fibromyalgia patients who practice on a continued and regular basis. The practiced meditator can achieve the following physical benefits:

Reduced heart rate, blood pressure, adrenaline levels, and skin temperature while meditating.
Improved well-being.
Better sleep -- some research has reported an increase in melatonin levels in experienced meditators. Melatonin is important in regulating the sleep-wake cycle.
Less pain, possibly from reductions in levels of cortisol, a stress hormone.

An important goal for both religious and therapeutic meditation practices is to quiet the mind, essentially to relax thought. This redirection of brain activity from thoughts and worries to the senses disrupts the stress response and prompts relaxation and renewed energy. Several meditation techniques are available. Some may be more useful for fibromyalgia than others.

Breath meditation. Other meditative forms involve focusing on the present moment and observing (but not examining or judging) one's thoughts. During breath meditation, one sits upright with the spine straight and the eyes closed. The subject begins to breathe regularly and continues to observe the outward exhalation of the breath. As the mind wanders, one simply notes the thoughts as a fact and returns to the breath. A variant of this technique called mindfulness meditation has been helpful for fibromyalgia patients. It involves focusing on the present moment and letting thoughts pass without the accompanying breathing exercises.
Fixed point meditation involves focusing on a stationary object, mental image (such as a candle flame), or internal sound (such as a mantra). When the mind begins to wander, the meditator gently brings concentration back to the central image or sound. This exercise promotes focus, but it is often experienced as a thinking exercise. A popular variety of this type of meditation is known as transcendental meditation, or TM.
Mini-meditation. This method involves heightening awareness of the immediate surrounding environment. One should first choose a simple routine activity when alone. For example, while washing dishes concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience, such as sounds outside the window, smells from the stove, or colors in the room. If the mind begins to think about the past or future, abstractions, or worries, redirect it gently back.

People who try meditation for the first time should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in the early evening before dinner. Even once a day is helpful. A person should probably not meditate before going to bed, because it causes some people to wake up in the middle of the night, alert and unable to return to sleep.

Hypnosis. In one small, short-term controlled study, hypnosis was more effective than physical therapy in improving function and reducing pain.

Massage Therapy. Massage therapy is thought to stimulate the parasympathetic nervous system, which slows down the heart and relaxes the body. In one study, patients who were given 30-minute massage sessions twice a week experienced lower stress and anxiety and less pain after 5 weeks compared to a group receiving an alternative therapy called transcutaneous electrical stimulation (TENS).

Because of the difficulties in treating fibromyalgia, many patients seek alternative therapies. Everyone should be wary of those who promise a quick cure or urge the purchase of expensive but potentially dangerous treatments.

Although some studies have reported benefit from these treatments, there is not enough evidence to recommend them. In one analysis, evidence was weakest on the advantages of so-called manipulative ("hands-on") approaches, such as chiropractic treatments.

Acupuncture. Studies continue to report conflicting results on acupuncture's ability to relieve pain. Several small studies suggest that it offers some benefit, especially to those who cannot take medicines because of their side effects. A larger controlled study found that inserting needles at fibromyalgia-related pressure points was no better at relieving pain for fibromyalgia than randomly inserting needles ("sham acupuncture"). A 2006 review of five randomized, controlled trials did not find enough evidence to support the use of acupuncture for fibromyalgia.

Click the icon to see an image of acupuncture.

Chiropractic or Osteopathic Manipulation. Chiropractic or osteopathic manipulation may also help some patients. While some studies have reported pain relief and improved sleep with osteopathic manipulation, larger controlled studies are needed to clearly identify whether manipulation is an effective treatment. Osteopathic techniques may include manipulation of the spine or muscle tissue release. Note that there is always some very small risk for adverse effects from any of these techniques. For example, in rare cases manipulation of the neck has caused stroke or damage to the large blood vessels in the neck.

Hydrotherapy and Similar Treatments. Hydrotherapy, also called balneotherapy, involves soaking in water, such as hot tubs, pools, or baths, to help relieve pain.

Herbal or Natural Remedies. Some alternative agents are being investigated for fibromyalgia:

Melatonin, a natural hormone associated with the sleep-wake cycle, may have benefits for some patients with fibromyalgia.
S-adenosylmethionine (SAMe) is a natural substance that has antidepressant, anti-inflammatory, and analgesic properties. It has shown some benefit in controlled studies.

It is extremely important for patients to realize that any herbal remedy or natural medicine that has positive effects most likely has negative side effects and toxic reactions, just as any conventional drug does. You should consult a doctor before using any untested products or dietary supplements. You should also discuss with your doctor any potential interactions between the supplements and any medications you take.

Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the U.S. Food and Drug Administration to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even deadly side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Behavioral Therapy

Studies continue to show that fibromyalgia patients feel better when they deal with the specific conditions of their disorder and their lives. Cognitive-behavioral therapy (CBT) enhances a patient's belief in their own abilities and helps them develop methods for dealing with stressful situations. CBT, also called cognitive therapy, is a known, effective method for dealing with chronic pain from arthritic conditions. Some evidence also suggests that cognitive-behavioral therapy can help some patients with fibromyalgia.

Although the effects of CBT and other non-medication treatments for fibromyalgia do not always last over the long-term, they may help certain groups of people, particularly those with a high level of psychological stress.

CBT may be particularly useful for addressing insomnia, one of the hallmark symptoms of fibromyalgia. Patients who received CBT for insomnia woke up 50% less at night, and had fewer symptoms of insomnia and improved mood.

The Goals of CBT. The primary goals of CBT are to change any unclear or mistaken ideas and self-defeating behaviors. Using specific tasks and self-observation, patients learn to think of pain as something other than a negative factor that controls their life. Over time, the idea that they are helpless against the pain goes away and, instead, they learn that they can manage the pain.

Cognitive therapy is particularly helpful in defining and setting limits -- a behavior that is extremely important for these patients. Many fibromyalgia patients live their lives in extremes. They first become heroes or martyrs, pushing themselves too far until they collapse. This collapse reverses the way they view themselves, and they then think of themselves as complete failures, unable to cope with the simplest task. One important aim of cognitive therapy is to help such patients discover a middle route. Patients learn to prioritize their responsibilities and drop some of the less important tasks or delegate them to others. Learning these coping skills can eventually lead to a more manageable life. Patients learn to view themselves and others with a more flexible attitude.

The Procedure. Cognitive therapy usually does not last long, typically 6 - 20 one hour sessions. Patients also receive homework, which usually includes keeping a diary and trying tasks they have avoided because of negative attitudes.

A typical cognitive therapy program may involve the following measures:

Keep a Diary. Patients are usually asked to keep a diary, a key part of cognitive therapy. The diary serves as a general guide for setting limits and planning activities. Patients use the diary to track any stress factors, such as a job or a relationship that may be making the pain worse or better.
Confront Negative or Discouraging Thoughts. Patients are taught to challenge and reverse negative beliefs. For example, "I'm not good enough to control this disease, so I'm a total failure" becomes the coping statement, "Where is the evidence that I can control this disease?"
Set Limits. Limits are designed to keep both mental and physical stress within manageable levels, so that patients do not become discouraged by getting "in over their heads." For example, tasks are broken down into incremental steps, and patients focus on one at a time.
Seek out Pleasurable Activities. Patients list a number of enjoyable low-energy activities that they can conveniently schedule.
Prioritize. Patients learn to drop some of the less critical tasks or delegate them to others.

Patients should learn to accept that relapses occur, and that over-coping and accomplishing too much too soon can often cause a relapse of symptoms. Patients should respect these relapses and back off. They should not consider them a sign of failure.

Research also shows that patient education can be effective in treating fibromyalgia, especially when combined with CBT, exercise, and other therapies. Educational programs can take the form of group discussions, lectures, or printed materials, although there isn't any clear evidence on which type of education works best.

Cognitive therapy may be expensive and not covered by insurance. Alternative and effective approaches that are free or less costly include strong, intelligently managed support groups or group psychotherapy. In one center, educational discussion groups were as effective, or even more so, than a cognitive therapy program. Such results are not typical in all centers, of course. Therapeutic success varies widely depending on the skill of the therapist.

Medications

Typically the first choice in drug treatment of fibromyalgia has consisted of an antidepressant or a muscle relaxant. The goal has been to improve sleep and pain tolerance. Medications from other drug classes (such as sleeping aids and pain relievers) may also be prescribed. Patients receive drug treatments in combination with exercise, patient education, and behavioral therapies. In 2007 the Food and Drug Administration approved Pregabalin (Lyrica) as the first drug for the treatment of fibromyalgia.

Pregabalin is an anti-epileptic. Also called anti-seizure drugs and anti-convulsants, these medicines affect the chemical messenger gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing.

Pregabalin was previously approved in 2004 to treat nerve pain and diabetic peripheral neuropathy. A 2005 study of 529 patients with fibromyalgia reported that 450 mg per day of pregabalin reduced pain and improved sleep quality and fatigue symptoms. Study results presented in November 2006 showed pregabalin cut fibromyalgia pain by at least 50% in 63% of patients, and the effect was long-lasting. The study, lasting 6 months, was one of the longest controlled studies of pregabalin in fibromyalgia to date. The most common side effects include mild-to-moderate dizziness and sleepiness. Pregabalin can impair motor function and cause problems with concentration and attention. Patients should talk to their doctor about whether pregabalin may impair their ability to drive.

Studies have shown that another anti-convulsant, gabapentin (Neurontin), which is approved for treatment of postherpetic neuralgia, affects pain transmission pathways and may relieve pain associated with fibromyalgia when compared with placebo. Patients who took gabapentin also reported that they slept better and were less tired.

The main classes of antidepressants used for treating fibromyalgia are tricyclics, selective serotonin-reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). Although these drugs are antidepressants, doctors prescribe them to improve sleep and relieve pain in non-depressed patients with fibromyalgia. The dosages used for managing fibromyalgia are generally lower than dosages prescribed for treating depression. If a patient has depression in addition to fibromyalgia, higher doses may be required.

Tricyclics. Tricyclic antidepressants cause drowsiness and can be helpful for improving sleep. The tricyclic drug most commonly used for fibromyalgia is amitriptyline (Elavil, Endep), which produces modest benefits with pain, but which can lose effectiveness over time. Other tricyclics include desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin), and nortriptyline (Pamelor, Aventyl).

Generally, only small doses of tricyclic antidepressants are needed to relieve fibromyalgia. Therefore, although tricyclics have several side effects, these side effects may be less frequent in fibromyalgia patients than in those taking tricyclics for depression. Side effects most often reported include:

Blurred vision
Difficulty urinating
Dizziness
Drowsiness
Dry mouth
Heart rhythm disturbances
Sexual dysfunction
Weight gain

As with all medications, tricyclics must be taken as directed. An overdose can be life-threatening.

Unfortunately, not all patients respond to tricyclics, and their effects wear off in some patients, sometimes after only a month.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) increase serotonin levels in the brain, which may have specific benefits for fibromyalgia patients. Commonly prescribed SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox). Studies suggest they may improve sleep, fatigue, and well-being in many patients. Studies are mixed on whether they improve pain. SSRIs should be taken in the morning, since they may cause insomnia. Common side effects are agitation, nausea, and sexual dysfunction, including delay or loss of orgasm and low sex drive.

Serotonin-Norepinephrine Reuptake Inhibitors. Serotonin-norepinephrine reuptake inhibitors (SNRIs) are also known as dual inhibitors because they act directly on two chemical messengers in the brain -- norepinephrine and serotonin. These drugs include:

Duloxetine (Cymbalta) is gaining attention as a treatment for fibromyalgia. In a 2004 study, 207 patients with fibromyalgia were randomized to receive either 60 mg of duloxetine twice a day or placebo for 12 weeks. Duloxetine significantly improved pain and tenderness and was effective for both depressed and non-depressed patients. Duloxetine was most effective for women, but very few men were enrolled in this trial.
Venlafaxine (Effexor) is similar to fluoxetine (Prozac) in effectiveness and tolerability for most patients. As with SSRIs, and unlike other newer antidepressants, venlafaxine impairs sexual function. Although clinical trials have shown that the drug is safe and effective in most people, there have been reports of changes in blood pressure. There have also been reports of problems with the electrical system of the heart when taking this drug. These side effects may cause serious problems in elderly patients. Some patients report severe withdrawal symptoms, including dizziness and nausea.
Milnacipran (Ixel) is under investigation and is not yet approved in the United States. It is specifically being researched for helping people with fibromyalgia and similar pain syndromes. In a 2004 study of 125 patients, milnacipran improved fibromyalgia pain and other symptoms, including fatigue, sleep, and depression.

Cyclobenzaprine (Flexeril) relaxes muscle spasms in specific locations without affecting overall muscle function. Cyclobenzaprine is related to the tricyclic antidepressants and has similar side effects, including drowsiness, dry mouth, and dizziness. A 2004 review of five randomized controlled trials found that patients who received cyclobenzaprine were three times more likely to report improvement in fibromyalgia symptoms than patients who received placebo.

Zolpidem (Ambien) or other newer sleep medications such as zaleplon (Sonata) and eszopiclone (Lunesta) may improve sleep for patients who suffer from insomnia.

Pain relief is of major concern for patients with fibromyalgia. Pain relievers for fibromyalgia include:

Tramadol (Ultram), used alone or in combination with acetaminophen (Tylenol), is commonly prescribed for relief of fibromyalgia pain. Its most common side effects are drowsiness, dizziness, constipation, and nausea. Tramadol should not be used in combination with tricyclic antidepressants.
For relief of mild pain, acetaminophen is most often recommended. Anti-inflammatory drugs, which are commonly used for arthritic conditions, are less useful for the pain of fibromyalgia, since the pain is not caused by muscle or joint inflammation. Anti-inflammatory drugs include corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen (Advil).
Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. Capsaicin is helpful in relieving painful areas in other disorders. It may have some value for fibromyalgia patients.
Opioids, or narcotics, may be used occasionally by certain patients with moderate-to-severe pain, or those with significant problems performing everyday tasks. Such patients should use narcotics only if they cannot find relief with other, less potent treatments. Some patients may get combinations of narcotic pain relievers and acetaminophen for periodic pain. Some physicians prescribe opioids, such as oxycodone (Roxicodone) or morphine sulfate (Duramorph), for patients who need ongoing relief. However, the benefit of opioids in fibromyalgia treatment is highly controversial. Physicians should take a careful medical and psychological profile of the patient before prescribing opioids. The patients should be evaluated periodically for continuing pain relief, side effects, and indications of dependence.
Pramipexole, a drug used to treat Parkinson’s disease and restless legs syndrome, may help relieve pain and fatigue in people with fibromyalgia, according to one study. Pramipexole stimulates production of dopamine, a chemical messenger in the brain. Researchers compared pramipexole with a dummy pill (placebo). After 3.5 months, 36% of those who took pramipexole said they felt much better, compared to 9% of those who received a dummy pill. Overall, patients had a 50% or greater decrease in pain.
One small 2005 study conducted in Spain suggests that the atypical antipsychotic olanzapine (Zyprexa) may be a beneficial add-on therapy for patients with fibromyalgia. Although proven effective for some chronic pain conditions, olanzapine and other antipsychotics cause unpleasant and potentially serious side effects.

Tropisetron. Tropisetron (Navoban) is a drug used to reduce vomiting during chemotherapy. European studies suggest that it may also help patients with fibromyalgia by reducing pain, dizziness, and depression, and by improving sleep. Fatigue and dizziness are the most common side effects.

Much of the pain patients experience occurs where muscles join tendons or bones, particularly when the muscles are stretched. Stretching or flexibility exercises are part of the warm-up and cool-down routines of any regular exercise program. Stretching techniques may also use injections or cooling agents to inactivate the pressure points so that muscles can be more effectively stretched. These techniques must be performed by a person other than the patient, usually a family member or close friend. With either injections or the spray, the benefits may last from a few days to weeks. Neither the spray nor the injection is useful without muscle stretching.

Spray and Stretch. One technique is known as "spray and stretch." This method uses the following approach:

The patient must be in a comfortable position.
The partner presses on suspected tender points and the patient reports any pain.
The points, when targeted, are sprayed with either ethyl chloride (Chloroethane) or Fluori-Methane. These chemicals are not numbing medicines. They cool the blood vessels in the skin to inactivate the tender points. Numbing skin creams do not appear to be effective for this treatment.
The spray bottle is held upside-down about 12 - 18 inches from the targeted area. The patient's face should be covered if the spray is being used near the head.
The patient's partner then slowly stretches the affected muscle.

After the procedure, the muscle should feel looser, and the patient should have a greater range of motion with that muscle.

Trigger-Point Injections. In some cases, "trigger-point injections" of a numbing drug, such as lidocaine, may be used for particularly painful tender points as an aid to stretching.

The injection causes intense, but brief, pain in the trigger point. After the medication has taken effect, however, the muscle's ability to stretch is much greater.
There is some soreness afterward, which can be severe. After an injection, spraying the whole muscle with cooling agents may inactivate less severe tender points.
In some cases, injections may be needed several times over 6 - 8 weeks.

Resources

www.rheumatology.org -- American College of Rheumatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.arthritis.org -- Arthritis Foundation
www.fmaware.org -- National Fibromyalgia Foundation
www.fmpartnership.org -- National Fibromyalgia Partnership
www.fmnetnews.com -- Fibromyalgia Network
www.aapainmanage.org -- American Academy of Pain Management
www.ampainsoc.org -- American Pain Society
www.medicalacupuncture.org -- American Association of Medical Acupuncture
www.asch.net -- American Society of Clinical Hypnosis
www.aabt.org -- Association for Advancement of Behavior Therapy
www.clinicaltrials.gov -- Find a clinical trial

References

Arnold LM, Goldenberg DL, Stanford SB, Lalonde JK, Sandhu HS, Keck PE, et al. Gabapentin in the treatment of fibromyalgia: a randomized, double-blind, placebo-controlled multicenter trial. Arthritis & Rheumatism. 2007;56:1336-1344.

Assefi NP, Sherman KJ, Jacobsen C, Goldberg J, Smith WR, Buchwald D. A randomized clinical trial of acupuncture compared with sham acupuncture in fibromyalgia. Ann Intern Med. 2005; 143(1): 10-9.

Da Costa D, Abrahamowicz M, Lowensteyn I, Bernatsky S, Dritsa M, Fitzcharles MA, Dobkin PL. A randomized clinical trial of an individualized home-based exercise programme for women with fibromyalgia. Rheumatology. 2005;44:1422-1427.

Harris RE, Clauw DJ. How Do We Know That the Pain in Fibromyalgia Is "Real"? Current Pain and Headache Reports. 2006;10:403-7.

Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, Zubieta JK. Decreased central u-opioid receptor availability in fibromyalgia. J Neurosci. 2007;27:10000-10006.

Holman AJ, Myers RR. A Randomized, Double-Blind, Placebo-Controlled Trial of Pramipexole, a Dopamine Agonist, in Patients With Fibromyalgia Receiving Concomitant Medications. Arthr Rheum. 2005; 52(: 2495-2505.

Mannerkorpi K, Henriksson C. Non-pharmacological treatment of chronic widespread musculoskeletal pain. Best Pract Res Clin Rheumatol. 2007;21:513-534.

McCabe CS, Cohen H, Blake DR. Somaesthetic disturbances in fibromyalgia are exaggerated by sensory-motor conflict: implications for chronicity of the disease? Rheumatology. 2007;46:1587-1592.

Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol Suppl. 2005;32(10):2063.

Rico-Villademoros F, Hidalgo J, Dominguez I, García-Leiva JM, Calandre EP. Atypical antipsychotics in the treatment of fibromyalgia: a case series with olanzapine. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29(1): 161-4.

Rooks DS, Gautam S, Romeling M, Cross ML, Stratigakis D, Evans B, et al. Group exercise, education, and combination self-management in women with fibromyalgia. Arch Intern Med. 2007;167;2192-2200.

Van Koulil S, Effting M, Kraaimaat FW, van Lankveld W, van Helmond T, Cats H, et al. Cognitive-behavioural therapies and exercise programmes for patients with fibromyalgia; state of the art and future directions. Ann Rheum Dis. 2007;66:571-581.

Zheng L, Faber K. Review of the Chinese medical approach to the management of fibromyalgia. Curr Pain Headache Rep. 2005;9(5): 307-12.

Review Date:
12/17/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

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