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Serotonin syndrome

admin — Thu, 04 Sep 2008 19:20:48 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Serotonin syndrome is a life-threatening drug reaction that causes the body to have too much serotonin, a chemical produced by nerve cells.

Alternative Names

Hyperserotonemia; Serotonergic syndrome

Causes, incidence, and risk factors

Serotonin syndrome most often occurs when two drugs that affect the body's level of serotonin are taken together at the same time. The drugs cause too much serotonin to be released or to remain in the brain area.

For example, you can develop this syndrome if you take migraine medicines called triptans together with antidepressants called selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SSNRIs). Popular SSRI's include Celexa, Zoloft, Prozac, Zoloft, Paxil, and Lexapro. SNRI's include Cymbalta, and Effexor. Brand names of triptans include Imitrex, Zomig, Frova, Maxalt, Axert, Amerge, and Relpax.

The FDA recently asked the manufacturers of these types of drugs to include warning labels on their products that tell you about the potential risk of serotonin syndrome. Talk to your doctor before stopping any medication.

Serotonin syndrome is more likely to occur when you first start or increase the medicine.

Older antidepressants called monoamine oxidase inhibitors (MAOIs) can also cause serotonin syndrome with the medicines describe above, as well as meperidine (a painkiller) or dextromethorphan (cough medicine).

Drugs of abuse, such as ecstasy and LSD (“acid”), have also been associated with serotonin syndrome.

Symptoms

Symptoms occur within minutes to hours, and may include:

Restlessness
Hallucinations
Loss of coordination
Fast heart beat
Rapid changes in blood pressure
Increased body temperature
Overactive reflexes
Nausea
Vomiting
Diarrhea

Signs and tests

The diagnosis is usually made by asking questions about your medical history, including the types of drugs you take.

To be diagnosed with serotonin syndrome, you must have been taking a drug that changes the body's serotonin levels (serotonergic drug) and have at least three of the following signs or symptoms:

Agitation
Uncoordinated movements (ataxia)
Heavy sweating not due to activity (diaphoresis)
Diarrhea
Overactive reflexes (hyperreflexia)
Fever
Mental status changes such as confusion or hypomania
Muscle spasms (myoclonus)
Shivering
Tremor

If you have just start taking or increased the dosage of a tranquilizer (neuroleptic drug), other conditions (such as neuroleptic malignant syndrome) will be considered. Serotonin syndrome is not diagnosed until all other possible causes have been ruled out, including infections, intoxications, metabolism problems, and drug withdrawal. Some symptoms of serotonin syndrome can mimic those due to an overdose of cocaine, lithium, or an MAOI.

Tests may include:

CBC
Thyroid function tests
Drug screen
Electrocardiogram (ECG)

Treatment

Patients with serotonin syndrome should stay in the hospital for at least 24 hours for close observation.

Treatment may include:

Withdrawal of medicines that caused the syndrome
Fluids by IV
Cyproheptadine (Periactin), a drug that blocks serotonin production
Benzodiazepines (muscle relaxants), such as Valium or Ativan, will be used to decrease agitation, seizure-like movements, and muscle stiffness

In life-threatening cases, medicines that keep your muscles still (paralyze them) and a temporary breathing tube and breathing machine will be needed to prevent further muscle damage.

Expectations (prognosis)

Patients may get slowly worse and can become severely ill if not quickly treated. Untreated serotonin syndrome can be deadly. However, with treatment, symptoms can usually go away in less than 24 hours.

Complications

Uncontrolled muscle spasms can cause severe muscle breakdown. The products produced when the muscles break down will build up in your blood and eventually go through the kidneys. This can cause severe kidney damage if not recognized and treated appropriately.

Calling your health care provider

Call your health care provider right away if you have symptoms of serotonin syndrome.

Prevention

Always tell all of your healthcare providers what medicines you take. Patients who take triptans with SSRIs or SNRIs should be closely followed, especially right after starting a medicine or increasing its dosage.

References

US Food and Drug Administration. FDA Public Health Advisory: Combined Use of 5-Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors (SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Life-threatening Serotonin Syndrome. Rockville, MD: Center for Drug Evaluation and Research; July 19, 2006.

Prator BC. Serotonin syndrome. J Neurosci Nurs. 2006 Apr;38(2):102-5.

Ford MD, Clinical Toxicology. 1st ed. Philadelphia, Pa: WB Saunders; 2001:150, 522, 547, 550.

Marx J. Rosen’s Emergency Medicine: Concepts and Clinical Practice. 5th ed. St. Louis, Mo: Mosby; 2002:2066.

Sternbach H. The Serotonin Syndrome. Am J Psychiatry. 1991: 148:705.

Parrot AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacol Biochem Behav. 2002 Apr;71(4):837-44. Review.

Review Date: 8/1/2006

Reviewed By: Eric Perez, MD, Department of Emergency Medicine, St. Luke's-Roosevelt Hospital Center, New York, NY. Review provided by VeriMed Healthcare Network.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Source Doc: 1_007272

Serum serotonin level

admin — Thu, 04 Sep 2008 19:12:09 -0700

Illustrations

Blood test

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Serotonin is a chemical produced by nerve cells. The serum serotonin level is a blood test to measure the amount of serotonin in your body.

Alternative Names

5-HT level; 5-hydroxytryptamine level; Serotonin test

How the test is performed

Blood is drawn from a vein, usually from the inside of the elbow or the back of the hand. The site is cleaned with germ-killing medicine (antiseptic). The health care provider wraps an elastic band around the upper arm to apply pressure to the area and make the vein swell with blood.

Next, the health care provider gently inserts a needle into the vein. The blood collects into an airtight vial or tube attached to the needle. The elastic band is removed from your arm.

Once the blood has been collected, the needle is removed, and the puncture site is covered to stop any bleeding.

In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding.

How the test will feel

When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing.

Why the test is performed

This test may be done to diagnose carcinoid syndrome. Many patients with carcinoid syndrome will have high levels of serotonin in blood and urine.

Normal Values

The normal range is 101-283 ng/ml (nanograms per milliliter)

What abnormal results mean

Higher-than-normal levels may indicate carcinoid syndrome.

What the risks are

Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others.

Other risks may include:

Excessive bleeding
Fainting or feeling light-headed
Hematoma (blood accumulating under the skin)
Infection (a slight risk any time the skin is broken)

Review Date: 5/17/2007

Reviewed By: Benjamin W. Van Voorhees, MD, MPH, Assistant Professor of Medicine, Pediatrics and Psychiatry, The University of Chicago, Chicago, IL. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_003562

Serotonin uptake

admin — Thu, 04 Sep 2008 19:41:52 -0700

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

Carcinoid syndrome is the pattern of symptoms that typically are exhibited by people with carcinoid tumors. The symptoms include bright red facial flushing, diarrhea, and occasionally wheezing. A specific type of heart valve damage can occur, as well as other cardiac problems. Carcinoid tumors secrete excessive amounts of the hormone serotonin. Surgery with complete removal of the tumor tissue is the ideal treatment. It can result in a permanent cure if it is possible to remove the tumor entirely.

Review Date: 9/11/2006

Reviewed By: Rita Nanda, M.D., Department of Medicine, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 2_9877

Another Reason to Eat Carbs: Boost Your Mood

FitSugar — Wed, 11 Nov 2009 03:00:56 -0800

The majority of Fit readers call themselves carb queens, and Winter can make those carbohydrate cravings even more intense. But have no fear: scientists are finding even more reasons not to avoid this essential food group.

A recent study of more than 100 obese and overweight adults in Australia found that dieting put people in a better mood; a drop in pounds led to increased satisfaction. But for people on low-carb diets, the mood boost didn't last.

The study group was split, with half the subjects on a lowfat diet and the other half low-carbing it. Interestingly, folks in both groups lost the same amount of weight on average, about 30 pounds. But after a year, the low-carb dieters also lost the positive mood effects, while the low-fat dieters did not. Here's more from the study.

Depression

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications of Depression...
Diagnosis
Treatment
Antidepressants and Drug Tr...
Psychotherapy
Other Treatments
Lifestyle Changes
Resources
References

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.

A.D.A.M. Copyright

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Anxiety disorders

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Complications
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, duloxetine (Cymbalta) was approved for treatment of generalized anxiety disorder. Duloxetine is a dual inhibitor antidepressant.

Anxiety Disorders Under-Recognized and Under-Treated

About 41% of patients with an anxiety disorder do not receive any treatment, indicates a 2007 study in the Annals of Internal Medicine. Anxiety disorders can interfere with daily functioning, and problems worsen when people have more than one type of anxiety disorder. The study’s researchers recommend that screening for anxiety become a regular part of office visits in the same way that primary care doctors screen patients for depression.

Antidepressants and Children

The benefits of antidepressants for treating pediatric anxiety disorders appear to outweigh the risks for suicide, according to a 2007 review in the Journal of the American Medical Association. Researchers also found that antidepressants did not work as well for treating obsessive compulsive disorder compared to other types of anxiety disorders. This review was the largest to date of antidepressant use in children and adolescents. Most doctors recommend cognitive behavioral therapy as the first treatment approach for childhood anxiety disorders.

Psychological Therapies for Post-Traumatic Stress Disorder

Specially designed psychotherapies -- such as trauma-focused cognitive behavioral therapy, eye movement desensitization and reprocessing, and stress management -- are the most effective therapies for patients with post-traumatic stress disorder, according to a 2007 review in the Cochrane Database.

Introduction

Fear and stress reactions are essential for human survival. They enable people to pursue important goals and to respond appropriately to danger. In a healthy individual, the stress response (fight, fright, or flight) is provoked by a genuine threat or challenge and is used as a spur for appropriate action.

An anxiety disorder, however, involves an excessive or inappropriate state of arousal characterized by feelings of apprehension, uncertainty, or fear. The word is derived from the Latin, angere, which means to choke or strangle. The anxiety response is often not attributable to a real threat. Nevertheless it can still paralyze the individual into inaction or withdrawal. An anxiety disorder persists, while a healthy response to a threat resolves, once the threat is removed.

Anxiety disorders have been classified according to the severity and duration of their symptoms and specific behavioral characteristics. Categories include:

Generalized anxiety disorder (GAD), which is long lasting and low-grade
Panic disorder, which has more dramatic symptoms
Phobias
Obsessive-compulsive disorder (OCD)
Post-traumatic stress disorder (PTSD)
Separation anxiety disorder (which is almost always seen in children)

GAD and panic disorder are the most common. Anxiety disorders are usually caused by a combination of psychological, physical, and genetic factors, and treatment is, in general, very effective.

Generalized anxiety disorder (GAD) is the most common anxiety disorder. It affects about 5% of Americans over the course of their lifetimes. It is characterized by the following:

A more-or-less constant state of worry and anxiety, which is out of proportion to the level of actual stress or threat in their lives.
This state occurs on most days for more than 6 months despite the lack of an obvious or specific stressor. (It worsens with stress, however.)
It is very difficult to control worry. For a clear diagnosis of GAD, the specific worries should be differentiated from those that would define other anxiety disorders, such as fear of panic attacks or appearing in public. Moreover, they are not obsessive like people with obsessive-compulsive disorder. (It should be noted, however, that over half of those with GAD also have another anxiety disorder or depression.)
Patients with anxiety may experience physical symptoms (such as gastrointestinal complaints) in addition to, or even in place of, mental worries. (This latter case may be more common in people from non-Western cultures such as those with Asian backgrounds.)
People with GAD tend to be unsure of themselves, overly perfectionist, and conforming.

Given these conditions, a diagnosis of GAD is confirmed if three or more of the following symptoms are present (only one for children) on most days for 6 months:

Being on edge or very restless
Feeling tired
Having difficulty with concentration
Being irritable
Having muscle tension
Experiencing disturbed sleep

Symptoms should cause significant distress and impair normal functioning and not be due to a medical condition, another mood disorder, or psychosis. It should be noted that pure GAD is uncommon. It typically occurs with other mood disorders (anxiety or depression) or substance use.

Panic disorder is characterized by periodic attacks of anxiety or terror (panic attacks). They usually last 15 - 30 minutes, although residual effects can persist much longer. The frequency and severity of acute states of anxiety determine the diagnosis. (It should be noted that panic attacks can occur in nearly every anxiety disorder, not just panic disorder. In other anxiety disorders, however, there is always a cue or specific trigger for the attack.) A diagnosis of panic disorder is made under the following conditions:

A person experiences at least two recurrent, unexpected panic attacks.
For at least a month following the attacks, the person fears that another will occur.

Symptoms of a Panic Attack. During a panic attack a person feels intense fear or discomfort with at least four or more of the following symptoms:

Rapid heart beat
Sweating
Shakiness
Shortness of breath
A choking feeling or a feeling of being smothered
Dizziness
Nausea
Feelings of unreality
Numbness
Either hot flashes or chills
Chest pain
A fear of dying
A fear of going insane

Women may be more likely than men to experience shortness of breath, nausea, and feelings of being smothered. More men than women have sweating and abdominal pain. Panic attacks that include only one or two symptoms, such as dizziness and heart pounding, are known as limited-symptom attacks. These may be either residual symptoms after a major panic attack or precursors to full-blown attacks. (It should be noted that panic attacks can also accompany other anxiety disorders, such as phobias and post-traumatic stress disorder. In such cases, however, additional characteristics differentiate these disorders from panic disorder.)

Frequency of Panic Attacks. Frequency of attacks can vary widely. Some people have frequent attacks (for example, every week) that occur for months; others may have clusters of daily attacks followed by weeks or months of remission.

Triggers of Panic Attacks. Panic attacks may occur spontaneously or in response to a particular situation. Recalling or re-experiencing even harmless circumstances surrounding an original attack may trigger subsequent panic attacks.

Phobias, manifested by overwhelming and irrational fears, are common. In most cases, people can avoid or at least endure phobic situations, but in some cases, as with agoraphobia, the anxiety associated with the feared object or situation can be incapacitating.

Agoraphobia. Agoraphobia has been somewhat misleadingly described as fear of open spaces, the term having been derived from the Greek word agora, meaning outdoor marketplace. In its severest form, agoraphobia is characterized by a paralyzing terror of being in places or situations from which the patient feels there is neither escape nor accessible help in case of an attack. (One patient described the terror of going outside as opening a door onto a landscape filled with snakes.) Consequently, people with agoraphobia confine themselves to places in which they feel safe, usually at home. The patient with agoraphobia often makes complicated plans in order to avoid confronting feared situations and places.

Social Phobia. Social phobia, also known as social anxiety disorder, is the fear of being publicly scrutinized and humiliated and is manifested by extreme shyness and discomfort in social settings. This phobia often leads people to avoid social situations and is not due to a physical or mental problem (such as stuttering, acne, or personality disorders). The incidence of social phobia is about 13% and has been termed "the neglected anxiety disorder" because it is often not properly diagnosed.

The associated symptoms vary in intensity, ranging from mild and tolerable anxiety to a full-blown panic attack. (Unlike a panic attack, however, social phobia is always directly related to a social situation.) Symptoms include sweating, shortness of breath, pounding heart, dry mouth, and tremor.

The disorder may be further categorized as generalized or specific social phobia:

Generalized social phobia is the fear of being humiliated in front of other people during nearly all social situations. People with this subtype are the most socially impaired and also the most likely to seek treatment.
Specific social phobia usually involves a phobic response to a specific event. Performance anxiety ("stage fright") is the most common specific social phobia and occurs when a person must perform in public. These patients usually feel comfortable in informal social situations.

Children with social anxiety develop symptoms in settings that include their peers, not just adults, and they may include tantrums, blushing, or not being able to speak to unfamiliar people. These children should be able to have normal social relationships with familiar people, however.

Specific Phobias. Specific phobias (formerly simple phobias) are an irrational fear of specific objects or situations. Specific phobias are among the most common medical disorders. Most cases are mild and not significant enough to require treatment.

The most common phobias are fear of animals (usually spiders, snakes, or mice), flying (pterygophobia), heights (acrophobia), water, injections, public transportation, confined spaces (claustrophobia), dentists (odontiatophobia), storms, tunnels, and bridges.

When confronting the object or situation, the phobic person experiences panicky feelings, sweating, avoidance behavior, difficulty breathing, and a rapid heartbeat. Most phobic adults are aware of the irrationality of their fear, and many endure intense anxiety rather than disclose their disorder.

Obsessive-compulsive disorder (OCD) has been described as hiccups of the mind. OCD is time-consuming, distressing, and can disrupt normal functioning. Much research suggests that a critical feature in this disorder is an overinflated sense of responsibility, in which the patient's thoughts center around possible dangers and an urgent need to do something about it.

Obsessions are recurrent or persistent mental images, thoughts, or ideas. The obsessive thoughts or images can range from mundane worries about whether one has locked a door to bizarre and frightening fantasies of behaving violently toward a loved one.
Compulsive behaviors are repetitive, rigid, and self-directed routines that are intended to prevent the manifestation of an associated obsession. Such compulsive acts might include repetitive checking for locked doors or unlit stove burners or calls to loved ones at frequent intervals to be sure they are safe. Some people are compelled to wash their hands every few minutes or to spend inordinate amounts of time cleaning their surroundings in order to subdue the fear of contagion.

Over half of OCD-sufferers have obsessive thoughts without the ritualistic compulsive behavior. Although individuals recognize that the obsessive thoughts and ritualized behavior patterns are senseless and excessive, they cannot stop them in spite of strenuous efforts to ignore or suppress the thoughts or actions. OCD often accompanies depression or other anxiety disorders. There is some evidence that the symptoms improve over time and that nearly half will eventually recover completely or have only minor symptoms.

Symptoms in children may be mistaken for behavioral problems (taking too long to do homework because of perfectionism, refusing to perform a chore because of fear of germs). Children do not usually recognize that their obsessions or compulsions are excessive.

Associated Obsessive Disorders. Certain other disorders that may be part of, or strongly associated with, the OCD spectrum include the following:

Body dysmorphic disorder (BDD). In BDD, people are obsessed with the belief that they are ugly, or part of their body is abnormally shaped.
Hypochondriasis. People who have hypochondiasis have an excessive fear of having a serious disease.
Anorexia nervosa. OCD frequently accompanies this eating disorder, where the compulsive behavior focuses on food restriction and thinness.
Trichotillomania. People with trichotillomania continually pull their hair, leaving bald patches.
Tourette syndrome. Symptoms of Tourette syndrome include jerky movements, tics, and uncontrollably uttering obscene words.

Obsessive-Compulsive Personality. OCD should not be confused with obsessive-compulsive personality, which defines certain character traits (being a perfectionist, excessively conscientious, morally rigid, or preoccupied with rules and order). These traits do not necessarily occur in people with obsessive-compulsive disorder.

Post-traumatic stress disorder (PTSD) is a severe, persistent emotional reaction to a traumatic event that severely impairs one’s life. It is classified as an anxiety disorder because of its symptoms. Not every traumatic event leads to PTSD, however. There are two criteria that must be present to qualify for a diagnosis of PTSD:

The patient must have directly experienced, witnessed, or learned of a life-threatening or seriously injurious event.
The patients' response is intense fear, helplessness, or horror. Children may behave with agitation or with disorganized behavior.

Triggering Events. PTSD is triggered by violent or traumatic events that are usually outside the normal range of human experience. There is some evidence that events most likely to trigger PTSD are those that involve deliberate and destructive behavior (murder, rape) and those that are prolonged or physically challenging. Such events include, but are not limited to, experiencing or witnessing sexual assaults, accidents, military combat, natural disasters (such as earthquakes), or unexpected deaths of loved ones. PTSD may also occur in people who have serious illness and receive aggressive treatments or who have close family members or friends with such conditions.

Symptoms of PTSD. There are three basic sets of symptoms associated with PTSD. They may begin immediately after the event or can develop up to a year afterward:

Re-experiencing. In such cases, patients persistently re-experience the trauma in at least one of the following ways: in recurrent images, thoughts, flashbacks, dreams, or feelings of distress at situations that remind them of the traumatic event. Children may engage in play, in which traumatic events are enacted repeatedly.
Avoidance. Patients may avoid reminders of the event, such as thoughts, people, or any other factors that trigger recollection. They tend to have an emotional numbness, a sense of being in a daze or of losing contact with their own identity or even external reality. They may be unable to remember important aspects of the event.
Increased Arousal. This includes symptoms of anxiety or heightened awareness of danger (sleeplessness, irritability, being easily startled, or becoming overly vigilant to unknown dangers).

To further qualify for a diagnosis of PTSD, patients must have at least one symptom in the re-experiencing category, three avoidance symptoms, and two arousal symptoms. Symptoms are chronic (3 months or more). Symptoms should also not be associated with alcohol, medications, or drugs and should not be intensifications of a pre-existing psychological disorder.

Acute Stress Disorder. Experts have identified a syndrome called acute stress disorder, in which symptoms of PTSD occur within 2 days to 4 weeks after the traumatic event. Acute stress disorder can accurately identify up to 94% of victims at risk for PTSD. Between 50 - 80% of these patients actually develop the more chronic and serious disorder. In other words, it is very sensitive for identification of those at highest danger for PTSD but less successful in determining specifically who will or will not recover emotionally.

Long-Term Outlook. The long-term impact of a traumatic event is uncertain. In one study of people who survived a mass killing spree in Texas, less than half of those who suffered PTSD (28% of all survivors) had recovered after a year. In another study, PTSD became chronic in 46% of the subjects. In fact, PTSD may cause physical changes in the brain, and in some cases the disorder can last a lifetime.

Separation anxiety disorder almost always occurs in children. It is suspected in children who are excessively anxious about separation from important family members or from home. For a diagnosis of separation anxiety disorder, the child should also exhibit at least three of the following symptoms for at least 4 weeks:

Extreme distress from either anticipating or actually being away from home or being separated from a parent or other loved one
Extreme worry about losing or about possible harm befalling a loved one
Intense worry about getting lost, being kidnapped, or otherwise separated from loved ones
Frequent refusal to go to school or to sleep away from home
Physical symptoms such as headache, stomach ache, or even vomiting, when faced with separation from loved ones

Separation anxiety often disappears as the child grows older, but if not addressed, it may lead to panic disorder, agoraphobia, or combinations of anxiety disorders.

Studies suggest that an imbalance of certain substances called neurotransmitters (chemical messengers in the brain) may contribute to anxiety disorders. The neurotransmitters targeted in anxiety disorders are gamma-aminobutyric acid (GABA), serotonin, dopamine, and epinephrine. Serotonin appears to be specifically important in feelings of well-being, and deficiencies are highly related to anxiety and depression.

Examples of study findings on some neurotransmitters are:

Abnormalities in the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin may have a particular role in susceptibility to generalized anxiety disorder. GABA helps prevent nerve cells from over-firing and serotonin is a brain chemical important in feelings of well-being.
Serotonin is a major player in OCD.
Changes in serotonin and dopamine have been observed in social phobia.
People with post-traumatic stress disorder have abnormalities in stress hormones (cortisol) and neurotransmitters associated with stress (epinephrine and norepinephrine). Such imbalances could account for the higher anxiety levels and a tendency to startle easily after a threat in people with PTSD.
Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is thought to be involved in depression and anxiety by causing changes in serotonin levels.

The best way to envision the brain's response to a threat is to imagine a primal situation, such as being chased by a bear.

The Brain's Response to Acute Stress. 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 marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

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

Catecholamines activate the amygdala, a small structure deep in the brain, which regulates control of major emotional activities, including anxiety, depression, aggression, and affection. In fact, the amygdala is sometimes known as the "fear" center.

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 to the bear, either to fight or to flee from it. (It also hinders the ability to handle complex 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 (the large bear) would be critical for avoiding such threats in the future.

Response by the Heart, Lungs, and Circulation to Acute Stress. 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 Immune System's Response to Acute Stress. The effect on the immune system from confrontation with the bear is similar to marshaling a defensive line of soldiers to potentially critical areas. The steroid hormones dampen parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be redistributed. These immune-boosting troops are sent to the body’s front lines where injury or infection is most likely, such as the skin, the bone marrow, and the lymph nodes.

The Acute Response in the Mouth and Throat. 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 Skin's Response to Acute Stress. The stress effect diverts blood flow away from the skin to support the heart and muscle tissues. (This also reduces blood loss in the event that the bear catches up.) The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Metabolic Response to Acute Stress. Stress shuts down digestive activity, a nonessential body function during short-term periods of physical exertion or crisis.

The Relaxation Response: the Resolution of Acute Stress. Once the threat has passed and the effect has not been harmful (the bear has not eaten or seriously wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also normalize.

Causes

A person's genetics, biochemistry, environment, history, and psychological profile all seem to contribute to the development of anxiety disorders. Most people with these disorders seem to have a biological vulnerability to stress, making them more susceptible to environmental stimuli than the rest of the population.

Abnormalities in the Brain. Scientists are using imaging techniques, particularly magnetic resonance imaging (MRI), to identify different areas of the brain associated with anxiety responses.

An MRI (magnetic resonance imaging) of the brain creates a detailed image of the complex structures in the brain. An MRI can give a three-dimensional depiction of the brain, making location of problems such as tumors or aneurysms more precise.

Important research in anxiety disorders is focusing on changes in the amygdala, which is sometimes referred to as the "fear center." This part of the brain regulates fear, memory, and emotion and coordinates these resources with heart rate, blood pressure, and other physical responses to stressful events. Some evidence suggests that the amygdala in people with anxiety disorders is highly sensitive to novel or unfamiliar situations and reacts with a high stress response.

Obsessive-compulsive disorder (OCD) is the anxiety disorder most strongly associated with specific brain dysfunction. For example, abnormalities in a specific pathway of nerves have been linked to OCD, attention deficit disorder, and Tourette syndrome. The symptoms of the three disorders are similar and they often coexist.

A number of imaging studies have reported less volume in the hippocampus in people with post-traumatic stress disorder. This important region is related to emotion and memory storage.

The influence of the family on anxiety is complicated by both genetic and psychological factors.

Panic Disorder and Family Influence. Certain psychodynamic theories suggest, and a few studies support the idea, that some people may develop panic disorder if they cannot resolve the early childhood conflict of dependence vs. independence. In one study, for example, young adults who had experienced childhood anxiety were more likely to live with their parents until their early to mid-twenties. Many people with panic disorder perceive their parents as being extremely controlling and overly protective while showing little actual affection.

Phobias and Family Influence. Several studies show a strong correlation between a parent's fears and those of the offspring. Although an inherited trait may be present, some researchers believe that many children can "learn" fears and phobias, just by observing a parent or loved one's phobic or fearful reaction to an event. People who have social phobias and severe agoraphobia generally report less parental affection and more strictness, overprotection, and encouragement of dependence than those without these disorders.

Obsessive-Compulsive Disorder and Family Influence. One study found that parental influence played no part in obsessive-compulsive disorder if the OCD patient was also not suffering from depression. However, depression coexists in two-thirds of OCD patients, and in the study patients who had both OCD and depression reported lower levels of parental care and overprotectiveness.

Traumatic events generally trigger anxiety disorders in individuals who are susceptible to them because of psychological, genetic, or biochemical factors. The clearest example is post-traumatic stress disorder. Specific traumatic events in childhood, particularly those that threaten family integrity, such as spousal or child abuse, can also lead to other anxiety and emotional disorders. Some individuals may even have a biological propensity for specific phobias, for instance of spiders or snakes, that have been triggered and perpetuated after a single exposure.

The acronym PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a term for an autoimmune condition associated with group A streptococcal infection in children (the cause of "strep throat" and rheumatic fever). Children with PANDAS develop tic-related disorders, including OCD and Tourette syndrome. In such cases, the OCD symptoms develop abruptly soon after the infection. It is unlikely to be an important cause of OCD.

Risk Factors

As many as 25% of all American adults experience intense anxiety sometime in their lives. The prevalence of true anxiety disorders is much lower, although they are still the most common psychiatric conditions in the United States and affect more than 20 million Americans.

Gender. With the exception of obsessive-compulsive disorder (OCD), women have twice the risk for most anxiety disorders as men. A number of factors may increase the reported risk in women, including cultural pressures to meet everyone else's needs except their own, and fewer self-restrictions on reporting anxiety to doctors.

Age. In general, phobias, OCD and separation anxiety show up early in childhood, while social phobia and panic disorder are often diagnosed during the teen years. Studies suggest that 3 - 5% of children and adolescents have some anxiety disorder. Children and adolescents who have an anxiety disorder are at risk of later developing other anxiety disorders, depression, and substance abuse.

Personality Factors. Children's personalities may indicate higher or lower risk for future anxiety disorders. For example, research suggests that extremely shy children and those likely to be the target of bullies are at higher risk for developing anxiety disorders later in life. Children who cannot tolerate uncertainty tend to be worriers, a major predictor of generalized anxiety. In fact, such traits may be biologically based and due to a hypersensitive amygdala -- the "fear center" in the brain.

Family History and Dynamics. Anxiety disorders tend to run in families. Genetic factors may play a role in some cases, but family dynamics and psychological influences are also often at work.

Social Factors. Several studies have reported a significant increase in anxiety levels in children and college students in the past two decades compared to children in the 1950s. In several studies, anxiety was associated with a lack of social connections and a sense of a more threatening environment. It also appears that more socially alienated populations have higher levels of anxiety. For example, a study of Mexican adults living in California reported that native-born Mexican Americans were three times more likely to have anxiety disorders (and even more likely to be depressed) as those who had recently immigrated to the U.S. The longer the immigrants lived in the U.S., the greater their risk for psychiatric problems. Traditional Mexican cultural and social ties seemed to protect recently arrived immigrants from mental illness.

Genetic Factors. Up to 50% of people with panic disorder and 40% of patients with generalized anxiety (GAD) have close relatives with the disorder. (About half of GAD patients also have family members with panic disorder, and about 30% have relatives with simple phobias.)

Obsessive-compulsive disorder (OCD) is also strongly related to a family history of the disorder. Close relatives of people with OCD are up to 9 times more likely to develop OCD themselves. Researchers are making progress in identifying specific genetic factors that might contribute to an inherited risk. Of particular interest are genes that regulate specific neurotransmitters (brain chemical messengers), including serotonin and glutamate. Recent research has suggested that the SLC1A1 gene, which is associated with glutamate regulation, may play an important role in early-onset OCD in boys. Research is also beginning to pinpoint regions on specific chromosomes (1, 3, 7, 6, 9, 15) that may contain genes linked to OCD.

However, there are no genetic tests to date that can identify patients at risk for anxiety disorders.

Medical Conditions. Although no causal relationships have been established, certain medical conditions have been associated with panic disorder. They include migraines, obstructive sleep apnea, mitral valve prolapse, irritable bowel syndrome, chronic fatigue syndrome, and premenstrual syndrome.

GAD affects about 1 - 5% of Americans in the course of their lives and is more common in women than in men. Some experts believe that it is underdiagnosed and more common than any other anxiety disorder. It is certainly the most common anxiety disorder among the elderly. GAD usually begins in childhood and often becomes a chronic ailment, particularly when left untreated. Depression in adolescence may be a strong predictor of GAD in adulthood. Depression commonly accompanies this anxiety disorder in any case.

Age and Panic Disorder. Studies indicate that the prevalence of panic disorder among adults is between 1.6 - 2% and is much higher in adolescence, 3.5 - 9%. Panic disorder usually first occurs either in late adolescence or in the mid-30s.

Gender and Panic Disorder. Women have about twice the risk for panic disorder as men. Panic attacks are very common after menopause. In one study, nearly 18% of older women reported panic attacks within a 6-month period, with over half of these attacks being full-blown. They tended to be associated with stressful life events and poor health. The effects of pregnancy on panic disorder appear to be mixed. It seems to improve the condition in some women and worsen it in others.

Obsessive-compulsive disorder occurs equally in men and women, and it affects about 2 - 3% of people over a lifespan. Most cases of OCD first develop in childhood or adolescence, although the disorder can occur throughout the life span.

Social anxiety disorder is currently estimated to be the third most common psychiatric disorder in the U.S. Studies have reported a prevalence of 7 - 12% in Western nations.

Age and Phobias. The onset of social anxiety disorder is usually during the early teenage years.

Gender and Phobias. Women are more likely to develop social anxiety disorder than men, although equal numbers of men and women seek treatment for it. Most people seeking treatment have had symptoms for at least 10 years.

Studies estimate a lifetime risk for PTSD in the U.S. of up to 8%. People exposed to traumatic events, of course, are at highest risk, but many people can go through such events and not experience PTSD. Studies estimate that 6 - 30% or more of trauma survivors develop PTSD, with children and young people being among those at the high end of the range. Women have the twice the risk of PTSD as men.

Furthermore, PTSD can occur in people not directly involved with a traumatic event. For example, 17% of the U.S. population outside New York City reported some symptoms of post-traumatic stress 2 months after the September 11 attack on the World Trade Towers. (In the city itself, where the attack occurred, an estimated 7.5% of New York's population reported PTSD within the month of the event, which declined to 0.6% at 6 months.)

Researchers are trying to determine factors that might increase vulnerability to catastrophic events and put people at risk for develop PTSD. Some studies report the following may be risk factors:

Pre-existing emotional disorder. People who have a history of an emotional disorder, particularly depression, before the traumatic event are at higher risk for PTSD.
Drug or alcohol abuse
A family history of anxiety
A history of abuse, particularly that which threatens family integrity, such as spousal or child abuse. Studies of individuals who had suffered physical or sexual abuse or neglect as children suggest that up to one-third develop PTSD.
An early separation from parents
Lack of social support and poverty
Sleep disorders. Insomnia and excessive daytime sleepiness even within a month after a traumatic event are important predictors for the development of PTSD. One specific sleep disorder -- sleep apnea -- may even intensify symptoms of PTSD, including sleeplessness and nightmares. Sleep apnea occurs when tissues in the upper throat (or airway) collapse at intervals during sleep, thereby blocking the passage of air. In one study, 91% of crime victims with PTSD had either sleep apnea or a lesser condition that partially blocked the airways during sleep. In fact, in one study treatment of sleep apnea eased PTSD. Sleep apnea has also been associated with a risk for panic disorder. [For more information, see In-Depth Report #65: Sleep apnea.]

Complications

Studies consistently report that all types of anxiety disorders can be very debilitating and seriously affect a person’s quality of life.

Depression. Depression is very common in people with an anxiety disorder, and it is sometimes difficult to distinguish one from the other because either or both can be accompanied by anxious feelings, agitation, insomnia, and problems with concentration.

Depression and nearly every anxiety disorder often go hand in hand, in both the young and old. In fact, the lifetime risk for depression in people with anxiety disorders may be higher than 70%. Furthermore, the combination of depression and anxiety is a major risk factor for both substance abuse and suicide. The following are examples of depression in specific anxiety disorders:

Between 50 - 65% of people with panic disorder also have major depression. Some studies have suggested that treating panic disorder early enough may help prevent major depression later on.
More than two-thirds of OCD patients suffer from depression.
Most patients with GAD will experience at least one episode of significant depression and many develop recurrent episodes. In patients with both disorders, GAD usually precedes the onset of depression.
Social anxiety during adolescence or young adulthood has been associated with a higher risk for depression, and the presence of both increases the chances for severe depression.
People with PTSD are four to seven times as likely to be depressed as are people without PTSD.

Bipolar Disorder. Symptoms of panic disorder are very common in people with bipolar disorder (manic-depression). In fact, people with bipolar have 26 times the rate of panic disorder as in the general population. Furthermore, anxiety worsens bipolar disorder. According to one study, anxiety disorders in teenagers were associated with bipolar disorder in adulthood, while manic behavior in adolescence was linked to later anxiety disorders.

Evidence now strongly supports an association between panic disorder and a risk for suicidal thoughts. Studies report that up to 18% of people with panic disorder attempt suicide and up to 38.5% regularly harbor suicidal thoughts, with the risks being higher in people with both panic disorder and depression. One study reported suicide attempts in about 12% of people with social phobias or OCD. If a person has an anxiety disorder and a mood disorders (such as depression), the risk for suicide is even higher.

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 commonly associated 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, unsuccessful 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

In one study, adolescents failed to seek help for suicidal thoughts for the following reasons:

They believed nothing would help.
They were reluctant to tell anyone they had problems.
They thought it was a sign of weakness to seek help.
They did 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.

[For more information on suicide, see In-Depth Report #8: Depression.]

Severely depressed or anxious people are at high risk for alcoholism, smoking, and other forms of addiction. Anxiety disorders are highly prevalent among people with alcoholism. Moreover, long-term alcohol use can itself cause biologic changes that may actually produce anxiety and depression.

Risk for Substance Abuse in Specific Anxiety Disorders. The following are some observations on specific anxiety disorders and substance abuse:

Some people with GAD and panic disorders may use alcohol or drugs to self-medicate.
Social phobia appears to pose a particular risk for alcohol abuse. People with this disorder are likely to drink in order to boost confidence. Alcohol itself has no direct beneficial effect on anxiety, but studies suggest that the belief in its effect appears to relieve anxious feelings. (Alcohol or substance abuse is not associated with specific phobias -- such as a fear of flying or spiders.)
Heavy smoking and substance abuse are common in people with PTSD. In adolescents, the disorder not only increases the risk for drug and alcohol use but also for eating disorders.

Studies consistently report that anxiety disorders have negative effects on work and relationships. Some examples:

In one study, more than 10% of patients with GAD missed at least 6 days of work within the previous month.
In a survey of OCD sufferers, 40% reported that they had to stop working because of the disorder. Only 40% worked full-time, while only half were married.
A 2006 study indicated that children with OCD are more likely to be bullied than other children.
Studies report that people with social phobias are less likely to get married, to leave home, and to finish school than those without this disorder. Their outlook worsens if they have other emotional disorders.

Anxiety disorders are associated with many different physical illnesses. Research suggests that people who have both an anxiety disorder and a physical illness have a worse quality of life and greater risk for disability than those who have only a physical illness. Anxiety disorders often tend to occur before the development of physical disorders.

Heart Disease. Anxiety has been associated with several heart problems, including unhealthy cholesterol levels, thicker blood vessels, and high blood pressure. Both anxiety and depression have been associated with a poorer response to treatment in heart patients, including a worse outcome after heart surgery.

Cholesterol is a soft, waxy substance that is present in all parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

Some researchers speculate that intense anxiety might trigger abnormal and dangerous heart rhythms in people with existing heart problems. In other studies, panic disorders, post-traumatic stress disorder, and phobias have been associated with a higher rate of sudden death from cardiac events, including heart attack.

Gastrointestinal Disorders. Anxiety frequently accompanies gastrointestinal conditions. Of note, half the cases of irritable bowel syndrome are associated with anxiety.

Headache. Both tension and migraine headaches are associated with anxiety disorders. One study reported that 32% of people with chronic tension headaches met criteria for anxiety. Similarly, another study reported that young girls with anxiety disorders were three times more likely to have chronic headaches than those without the disorder. (Headaches in both studies were also strongly associated with depression.)

Respiratory Problems. Studies report an association between anxiety in patients with obstructive lung conditions (asthma, emphysema, and chronic bronchitis) and more frequent relapses.

Obesity. Anxiety disorders may lead to obesity, and the reverse may also be true. A 2006 study suggested that anxiety disorders and depression in childhood may lead to higher body mass index (BMI) in adult women (but not men). Another 2006 study indicated that obesity is associated with a 25% increased risk of developing anxiety and mood disorders.

Allergic Conditions. Anxiety disorders are associated with numerous allergic conditions including hay fever, eczema, hives, food allergies, and conjunctivitis.

Other Conditions. Other physical conditions associated with anxiety disorders include thyroid problems and arthritis.

People with obsessive-compulsive disorders can experience skin problems from excessive washing, injuries from repetitive physical acts, and hair loss from repeated hair pulling (behavior known as trichotillomania).

Effect of PTSD on the Brain. Studies are reporting that PTSD is associated with shrinkage in the hippocampus, the part of the brain important for memory and learning. Some animal studies indicate that such damage may result from long-term exposure to cortisol, the major stress hormone. In one study, people who had suffered severe trauma scored 40% lower in tests of verbal memory than did the general population. There was no difference in IQ or in scores of other types of memory. Some studies suggest that exposure to chronic stress, common in PTSD patients, may even compromise the function of the brain’s receptors for anti-anxiety medication. On the other hand, a small hippocampal volume may itself increase stress hormone levels, so people with genetically smaller hippocampi may be susceptible to PTSD.

Effects of PTSD on Health. Studies of military veterans who have endured major traumatic events have found a higher risk for health problems. One study of Vietnam veterans reported that PTSD was associated with greater physical limitations, poorer physical health, and a lower quality of life than was found in the general population, regardless of other accompanying emotional or medical disorders. In another study of these veterans, PTSD sufferers had twice the risk for abnormal heart rhythms and four times the risk of a heart attack compared to men without PTSD.

Evidence suggests an association between anxiety in children and recurrent stomach aches. Anxiety has been associated with a higher risk for sleep disorders in children, such as frequent nightmares, restless legs syndrome, and bruxism (grinding and gnashing of the teeth during sleep).

Diagnosis

A physical examination and medical and personal history is essential. Because anxiety accompanies so many medical conditions, some serious, it is extremely important for the doctor to uncover any medical problems or medications that might underlie or be masked by an anxiety attack.

The patient should describe any occurrence of anxiety disorders or depression in the family and mention any other contributing factors, such as excessive caffeine use, recent life changes, or stressful events.

It is very important to be honest with your doctor about all conditions, including excessive drinking, substance abuse, or other psychological or mood states that might contribute to, or result from, the anxiety disorder.

Diagnosing children with an anxiety disorder can be very difficult, since anxiety often results in disruptive behaviors that overlap with attention-deficit hyperactivity or oppositional disorder. Other conditions with symptoms similar to anxiety disorders include pervasive developmental disorders such Asperger syndrome, learning disabilities, bipolar disorder, and depression. Many children have anxiety disorder and a co-occurring condition, which should be treated along with anxiety.

People with anxiety disorders are more likely to see a family doctor before a mental health specialist, since their symptoms are often physical. Symptoms can include muscle tension, trembling, twitching, aching, soreness, cold and clammy hands, dry mouth, sweating, nausea or diarrhea, or urinary frequency. Anxiety attacks can mimic or accompany nearly every acute disorder of the heart or lungs, including heart attacks and angina (chest pain). In fact, nearly all individuals with panic disorders are convinced that their symptoms are physical and possibly life-threatening.

Heart Problems. Studies suggest that up to a third of patients entering the emergency room with chest pain and who are low-to-moderate risk for a heart attack are actually suffering from panic attacks. It is often difficult even for specialists to distinguish between heart conditions and a panic attack:

Women who are having an actual heart attack or acute heart problem are much more likely to be misdiagnosed as having an anxiety attack than are men with similar symptoms.
Mitral valve prolapse, a common and usually mild heart problem, may have symptoms that are nearly identical to those of panic disorder. The two conditions, in fact, frequently occur together.

Mitral valve prolapse is a disorder in which the mitral valve does not close properly when the heart contracts. When the valve does not close properly it allows blood to backflow into the left atrium. Some symptoms can include palpitations, chest pain, difficulty breathing after exertion, fatigue, cough, and shortness of breath while lying down.

People with a heart-rhythm disturbance called paroxysmal supraventricular tachycardia have many of the same symptoms as those with panic attacks.

Asthma. Asthma attacks and panic attacks have similar symptoms and can also coexist.

Hyperthyroidism. Hyperthyroidism can cause many of the same symptoms of generalized anxiety disorder and must be ruled out.

Click the icon to see an image of hyperthyroidism.

Epilepsy. The symptoms of partial seizures and panic attacks often overlap.

Other Medical Conditions. In addition, anxiety-like symptoms are seen in many other medical problems, including hypoglycemia, recurrent pulmonary emboli, and adrenal-gland tumors. Women can also experience intense anxiety attacks with hot flashes during menopause.

Medication Side Effects. Many drugs, including some for high blood pressure, diabetes, and thyroid disorders, can produce symptoms of anxiety. Withdrawal from certain drugs, often those used to treat sleep disorders or anxiety, can also precipitate anxiety reactions.

Substance Abuse. People with anxiety disorders often drink alcohol or abuse drugs in order to conceal or eliminate symptoms, but substance abuse and dependency can also cause anxiety. In addition, withdrawal from alcohol can produce physiologic symptoms similar to panic attacks. Clinicians often have difficulty determining whether alcoholism or anxiety is the primary disorder. Overuse of caffeine or abuse of amphetamines can cause symptoms resembling a panic attack.

Clinicians use various screening tests to determine the causes, type, severity, and frequency of anxiety. Such tests include the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Penn State Worry Questionnaire, and the Yale-Brown Obsessive Compulsive Scale.

Treatment

Anxiety disorders require treatment. Simply trying to talk oneself out of anxiety is as futile as trying to talk oneself out of a heart or stomach problem. Most anxiety disorders, especially phobias, respond well to treatment. They may, however, require long-term treatment. Many patients have a recurrence and may require additional medications. Nevertheless, most patients do not receive appropriate care for anxiety disorders. Many patients do not receive any treatment at all.

The standard current approach to most anxiety disorders is a combination of cognitive-behavioral therapy (CBT) and an antidepressant medication. A selective serotonin reuptake inhibitor (SSRI) is typically the first choice, with the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor) an alternative. If patients do not respond to these drugs, tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs) may be helpful. Benzodiazepines may be recommended for patients who are not helped by antidepressants. A healthy lifestyle that includes exercise, adequate rest, and good nutrition can also help to reduce the impact of anxiety.


Anxiety Disorder	Medications	Cognitive-Behavioral Therapy (CBT) and other Non-Drug Therapies
Generalized Anxiety Disorder	Antidepressants, benzodiazepines, and buspirone are helpful but have varying side effects. Investigational drugs include pregabalin and other anticonvulsants.	Cognitive-behavioral therapy or anxiety management therapy. Anxiety management therapy involves education, relaxation training, and exposure to anxiety-provoking stimuli but does not include cognitive restructuring.
Panic Attacks	SSRIs are treatment of choice. If patients do not respond to SSRIs, short-term treatment with a benzodiazepine may be used, or patients may switch to another type of antidepressant such as venlafaxine or tricyclics.	Cognitive-behavioral therapy, provided in 12 - 16 sessions over 3 - 4 months, focuses on recreating fear symptoms and helping patients change their response to them.
Social Anxiety Disorder	SSRIs or venlafaxine are first-line drug treatments. Benzodiazepines may help patients who do not respond to these antidepressants. In severe cases, an MAOI antidepressant may be prescribed. Anticonvulsants such as gabapentin (Neurontin) and pregabalin (Lyrica) are being investigated.	Cognitive-behavioral therapy can help improve symptoms after 6 - 12 weeks.
Obsessive-Compulsive Disorder	SSRIs are the first choice for adults. Clomipramine (a tricyclic antidepressant) is an alternative for adult patients who do not respond to SSRIs. For children, SSRIs do not seem to work as well for OCD as for other types of anxiety disorders.	Cognitive-behavioral therapy is the first treatment choice for children. For adults, either CBT or drug therapy may be offered as initial treatment. CBT techniques focus on exposure and response prevention (ERP).
Post-Traumatic Stress Disorder	Antidepressants, particularly SSRIs (sertraline and paroxetine approved for PTSD). The atypical antipsychotic olanzapine may be added to an antidepressant for patients who do not respond to a SSRI alone.	Trauma-focused psychological treatments include exposure therapy, trauma-focused cognitive therapy, and eye movement desensitization and reprocessing.
Note: For anxiety disorders in adults, the most effective treatments are usually combinations of drugs and CBT techniques. For children, CBT is usually the first treatment.

Medications

Selective serotonin-reuptake inhibitors (SSRIs), or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine (Effexor), are the primary first-line treatment for anxiety disorders. For patients who are not helped by these drugs, benzodiazepines, either alone or in combination with an antidepressant, may be prescribed. Other types of antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), may also be used to treat patients with severe or chronic forms of anxiety disorders.

Drug therapies for anxiety disorders work best in combination with cognitive behavioral therapy.

Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs can cause agitation, nausea, and diarrhea. Sexual function side effects include low sex drive, inability to have an orgasm, and impotence. Over time, many SSRI-treated patients gain weight, although the degree of weight gain varies depending on the drug. Elderly people taking these drugs should take the lowest effective dose possible, and those with heart problems should be monitored closely.

There have been many concerns about SSRIs and increased risk for suicidal behavior. Both adults and children who are treated with SSRIs should be carefully monitored for any worsening of depressive symptoms or changes in behavior. This is especially important during the first few months of antidepressant treatment.

Paroxetine has been linked to heart-related birth defects when women took this drug during the first trimester of pregnancy. Experts are also advising caution in prescribing other types of SSRIs to pregnant women. While certain SSRIs may carry increased risks for some specific type of rare birth defects, research suggests that the overall risks are minimal. Still, women who are pregnant or who are considering becoming pregnant should discuss the potential risks of these drugs with their doctors.

Serotonin-norepinephrine reuptake inhibitors (SNRIs). SNRIs are known as dual inhibitors because they work on two neurotransmitters -- norepinephrine and serotonin. Venlafaxine (Effexor) is an SNRI that is approved for treatment of generalized anxiety disorder, social anxiety disorder, and panic disorder in adults. (It is not approved for children.) As with many SSRIs, venlafaxine impairs sexual function. Venlafaxine can increase blood pressure and heart rate and should be used with caution in patients with high blood pressure or heart disease. Some patients report severe withdrawal symptoms, including dizziness and nausea. This drug has a serious risk for overdose. Venlafaxine should not be taken during the last trimester of pregnancy because the drug can cause complications in newborn infants.

Duloxetine (Cymbalta) also acts on both serotonin and norepinephrine. In 2007, it was approved for treatment of generalized anxiety disorder. 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.

Mitrazapine (Remeron) is another type of SNRI that is sometimes used for treatment of post-traumatic stress disorder and social anxiety disorder.

Tricyclic Antidepressants. Tricyclics are an older type of antidepressant. Tricyclics used for treatment of anxiety disorder include imipramine (Tofranil, for generalized anxiety disorder, panic disorder), nortriptyline (Pamelor, for panic disorder), desipramine (Norpramin, for panic disorder), and clomipramine (Anafranil, for obsessive compulsive disorder). Clomipramine is approved specifically for OCD, but because of its severe side effects it is usually used only if SSRIs have failed to help.

Side effects of TCAs include sleep disturbance, abrupt reduction in blood pressure upon standing, weight gain, sexual dysfunction, and mental disturbance. Elderly patients and those with a history of seizures, cardiac problems, closed-angle glaucoma, and urinary retention or obstruction should be closely supervised when taking tricyclics.

Monoamine Oxidase Inhibitors. Monoamine oxidase inhibitors (MAOIs) are the oldest type of antidepressant. The MAOI phenelzine (Nardil) is sometimes used to treat social anxiety disorder or post-traumatic stress disorder that has not responded to other treatments.

MAOIs commonly cause weight gain, drowsiness, dizziness, sexual dysfunction, and insomnia. Dietary restrictions are the main problem with these drugs. Severe high blood pressure (hypertension) can be brought on by eating certain foods that have a high tyramine content, including cheese, red wine, and processed meats. High blood pressure can also occur when MAOIs are taken with certain drugs, including some common over-the-counter cough medications and decongestants. MAOIs can cause birth defects and should not be taken by pregnant women.

Most serious, fatal reactions can occur when MAOIs and SSRIs or venlafaxine are taken at the same time. There should be at least a 2- to 5-week break if a patient is changing from one type of antidepressant to the other.

Benzodiazepines are safe and effective medications for most anxiety disorders and have been the standard of treatment for years. However, their on-going use has been associated with a high risk for dependency and abuse. Therefore, they have been supplanted in most cases by SSRIs and other newer antidepressants. For anxiety disorders, benzodiazepines are most often used to treat panic disorder, and are sometimes used for social anxiety disorder and generalized anxiety disorder. These drugs include alprazolam (Xanax), clonazepam (Klonopin), and lorazepam (Ativan).

Benzodiazepines have many side effects, generally associated with chronic use. The most common are daytime drowsiness and a hung-over feeling. In rare cases, they can cause agitation. They may worsen respiratory problems. Benzodiazepines are potentially dangerous when used in combination with alcohol. Overdoses can be serious, although they are very rarely fatal.

The elderly are more susceptible to side effects and should usually start at half the dose prescribed for younger people. These drugs increase the risk of falling, which can increase the risk for hip fracture in older people. Also of concern are studies showing a high risk of automobile accidents in people who take benzodiazepines. Benzodiazepines taken during pregnancy are associated with birth defects, and they should not be used by pregnant women or by nursing mothers.

Loss of Effectiveness and Dependence. Eventually these drugs can lose their effectiveness with continued use at the same dosage. As a result, patients may want to increase their dosage to prevent anxiety. This causes dependency, which can occur after taking these drugs for several weeks.

Withdrawal and its Treatments. Withdrawal symptoms can be very severe, even in people who rapidly discontinue benzodiazepines after taking them for only 4 weeks. Symptoms include sleep disturbance and anxiety, which can develop within hours or days after stopping the medication. Some patients experience stomach distress, sweating, and insomnia, which can last 1 - 3 weeks. The longer the drugs are taken and the higher their dose, the more severe these symptoms can become. Simply tapering off gradually helps about 60% of people stop taking these drugs. Certain medications (anti-seizure drugs, antidepressants, buspirone) may also help with withdrawal.

Azapirones, such as buspirone (BuSpar), act on serotonin receptors called 5-HT(1A). Buspirone appears to work as well as a benzodiazepine for treating generalized anxiety disorder. It usually takes several days to weeks for the drug to be fully effective. It is not useful against panic attacks.

Buspirone does not produce any immediate euphoria or change in sensation, so some people believe, erroneously, that the drug doesn't work. Such qualities result in a very low potential for abuse. In fact, unlike the benzodiazepines, buspirone is not addictive, even with long-term use, so it may be particularly useful for the patient whose anxiety disorder coexists with alcoholism or drug abuse.

Buspirone also seems to have less pronounced side effects than benzodiazepines and no withdrawal effects, even when the drug is discontinued quickly. Common side effects include dizziness, drowsiness, and nausea. Buspirone should not be used with monoamine oxidase inhibitors (MAOIs).

Beta-blockers, including propranolol (Inderal) and atenolol (Tenormin), block the nerves that stimulate the heart to beat faster. They affect only the physiologic symptoms of anxiety (particularly rapid heart rate) and are most helpful for phobias, particularly performance anxiety. They may be taken before entering a situation where anxiety symptoms tend to occur. Beta-blockers are less effective for other forms of anxiety.

Atypical antipsychotics are mostly used for treating schizophrenia, bipolar disorder, and major depressive disorder. Doctors sometimes use the atypical antipsychotic olanzapine (Zyprexa) for treating severe cases of post-traumatic stress disorder. However, olanzapine has severe side effects, including weight gain and increased high blood sugar levels, which can increase the risk for diabetes. [For more information, see In-Depth Report #47: Schizophrenia.]

Pregabalin (Lyrica) and gabapentin (Neurontin) are drugs used to treat seizures and other conditions. Researchers are investigating whether these drugs may be useful for certain anxiety disorders, such as social anxiety disorder and general anxiety disorder. Their exact role in the treatment of anxiety disorders is not clear, however.

Studies indicate that the dietary supplement inositol may have benefits for panic disorder and, possibly, obsessive compulsive disorder. Inositol is part of the vitamin B complex.

Some patients use aromatherapy as a relaxation aid. Aromatherapy is in general safe, but some plant extracts in these formulas have been linked to skin allergies.

There is no evidence supporting the efficacy of valerian, St. John’s wort, or passionflower for treatment of anxiety. The herbal remedy kava has been associated with liver problems and should not be avoided, especially by patients with liver disease or those who use alcohol. Kava can also interact dangerously with medications that are metabolized by the liver.

Other Treatments

The goal of cognitive-behavioral therapy (CBT) is to regain control of reactions to stress and stimuli, thus reducing the feeling of helplessness that often accompanies anxiety disorders. CBT works on the principle that the thoughts that produce and maintain anxiety can be recognized and altered using various techniques that change behavioral responses and eliminate the anxiety reaction. Many studies have shown that a combination of CBT and medication works best for treating anxiety disorders.

A number of CBT approaches work well for treating many types of anxiety disorders. Studies suggest that CBT is also helpful for patients who have additional conditions, such as depression, a second anxiety disorder, or alcohol dependency. (It may take longer to achieve a successful outcome in such cases, however.) CBT is often given along with drug treatment. A study in the Journal of the American Medical Association found that children and adolescents with OCD responded better to CBT alone than the antidepressant setraline (Zoloft) alone, but most patients did best when they were treated with a combination of CBT and sertraline.

Both individual and group treatments work well. (However, people with social phobia may do better in individual sessions.) Several recent studies also indicate that telephone-based behavioral therapy works well for people with OCD, generalized anxiety disorder, and panic disorders.

Anxiety disorders are chronic, however, and recurrence is common. Some studies indicate that 30 - 82% of people with panic disorder and phobias have a recurrence of attacks at an average of 9 months, even after successful short-term therapy. Medications, then, are also generally recommended for most patients.

Basic Cognitive Therapy Techniques. Treatment usually takes about 12 - 20 weeks. The essential goal of cognitive therapy is to understand the realities of an anxiety-provoking situation and to respond to reality with new actions based on reasonable expectations.

First, the patient must learn how to recognize anxious reactions and thoughts as they occur. One way of accomplishing this is by keeping a daily diary that reports the occurrences of anxiety attacks and any thoughts and events associated with them. A patient with OCD, for instance, may record repetitive thoughts.
These entrenched and automatic reactions and thoughts must be challenged and understood. Again, using the OCD example, one approach is to record and play back the words of the repetitive thoughts, over exposing the patient to the thoughts and reducing their effect. One effective approach for patients with generalized anxiety disorder targets their intolerance of uncertainty and helps them develop methods to cope with it.
Patients are usually given behavioral homework assignments to help them change their behavior. For example, a person with generalized social phobia may be asked to buy an item and then return it the next day. As the patient performs this action, they observe any unrealistic fears and thoughts triggered by such an event.
As the patient continues with self-observation, they begin to perceive the false assumptions that underlie the anxiety. For example, OCD patients may learn to recognize that their heightened sense of responsibility for preventing harm in non-threatening situations is not necessary or even useful.
At that point, the patient can begin substituting new ways of coping with the feared objects and situations.

Systematic Desensitization. Systematic desensitization is a specific technique that breaks the link between the anxiety-provoking stimulus and the anxiety response. This treatment requires the patient to gradually confront the object of fear. There are three main elements to the process:

Relaxation training
A list composed by the patient that prioritizes anxiety-inducing situations by degree of fear
The desensitization procedure itself, confronting each item on the list, starting with the least stressful

This treatment is especially effective for simple phobias, social phobias, agoraphobia, and post-traumatic stress syndrome.

Exposure and Response Treatment. Exposure treatment purposefully generates anxiety by exposing the patient repeatedly to the feared object or situation, either literally or using imagination and visualization. It uses the most fearful stimulus first. (This differs from the desensitization process because it does not involve relaxation or a gradual approach to the source of anxiety.)

Exposure treatments are usually known as either flooding or graduated exposure:

Flooding exposes the person to the anxiety-producing stimulus for as long as 1 - 2 hours.
Graduated exposure gives the patient a greater degree of control over the length and frequency of exposures.

In both cases, the patient experiences the anxiety over and over until the stimulating event eventually loses its effect. Combining exposure with standard cognitive therapy may be particularly beneficial. This approach has helped certain patients in most anxiety disorder categories, including post-traumatic stress disorder.

Modeling Treatment. Phobias can often be treated successfully with modeling treatment:

The therapy typically uses an actor who approaches an anxiety-producing object or engages in a fear-provoking activity that is similar to the patient's specific problem. Either a live or videotaped situation may be used, although the live model is considered to be more effective.
The patient observes this event and tries to learn how to behave in a comparable manner.

Other forms of psychotherapy, commonly called emotion-based psychotherapy (EBT), psychodynamic therapy, or "talk" therapy, deal more with childhood roots of anxiety and usually, although not always, require longer treatments. They include interpersonal therapy, supportive psychotherapy, attention intervention, and psychoanalysis. All work is done during the sessions. Some research indicates that such therapies might be more useful for generalized anxiety, which may require more sustained work to process and recover from early traumas and fears. Studies suggest that although emotion-based psychotherapies are not as effective as cognitive-behavioral therapy (CBT) in treating panic disorders, patients tend to stay longer in EBT than in CBT. Some doctors suggest adding elements of EBT to the usual CBT and medication treatments.

Anxiety Management Therapy. Anxiety management therapy is sometimes used as an alternative to CBT for generalized anxiety disorder. It involves patient education, relaxation training, and exposure to anxiety-provoking stimuli but does not include exercises in cognitive retraining.

Relaxation Training. Relaxation techniques use muscle relaxation and mental visualization to help focus attention towards a calming feeling. Some people find meditation helpful.

Breathing Retraining. Breathing retraining techniques may help reduce the physical effects of anxiety. For example, hyperventilation is one of the primary physical manifestations of panic disorders. This involves rapid, tense breathing, resulting in chest pain, dizziness, tingling of the mouth and fingers, muscle cramps, and even fainting. By practicing measured, controlled breathing at the onset of a panic attack, patients may be able to prevent full attacks.

Biofeedback. Biofeedback uses special sensors that allow patients to recognize anxiety states by changes in specific physical functions, such as changes in pulse rate, skin temperatures, and muscle tone. Eventually they learn to modify these changes, which in turn helps relieve anxiety. While commonly used, there are not many rigorous studies showing that biofeedback helps patients reduce or eliminate their symptoms over the long term.

Several types of psychological treatments have been designed specifically for treating patients with PTSD. These approaches include a special type of CBT known as trauma-focused cognitive behavioral therapy (TFCBT), and a psychotherapy treatment called eye movement desensitization and reprocessing (EMDR).

With TFCBT, patients are taught stress management skills. The therapist helps the patient develop a narrative (verbal, written, or artistic) about the traumatic event. Patients may be exposed to reminders about the trauma and are taught how to cope with future reminders. Through the process, the patient learns how to reprocess their thoughts, feelings, and behaviors.

With EMDR, the patient focuses on remembering the traumatic experience while visually following the rhythmic movement of the therapist’s fingers. The patient recounts to the therapist what memories have been provoked during the exercise. EMDR may help patients recall details and sensations that they had blocked out. Through this breakthrough, patients learn how to regain emotional control.

Transcranial magnetic stimulation (TMS) uses high frequency magnetic pulses to target and stimulate specific areas of the brain. Research has particularly focused on possible benefits for obsessive-compulsive behavior. Some studies have found some improvement in mood, but more research is needed to determine its value for reducing anxiety and obsessions.

In 2006, the U.S. National Institutes of Health funded a large study to examine whether deep brain stimulation (DBS) can help patients with OCD. DBS involves implanting tiny stimulators into the brain to block abnormal nerve signals that cause obsessive symptoms. These “brain pacemakers” are approved to treat epilepsy and Parkinson’s disease. Researchers hope that DBS may eventually provide a new treatment option for patients with severe OCD.

A surgical technique called cingulotomy involves interrupting the cingulate gyrus, a bundle of nerve fibers in the front of the brain. It is sometimes used as a last resort for patients with severe OCD. A variation of this procedure using magnetic resonance imaging (MRI) to guide the surgeon has resulted in long-term improvement in about 25 - 33% of OCD patients in whom it is performed. The procedure is generally safe with few serious complications and does not affect intellect or memory.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.adaa.org -- Anxiety Disorders Association of America
www.nami.org -- National Alliance on Mental Illness
www.psych.org -- The American Psychiatric Association
www.apa.org -- The American Psychological Association
www.istss.org -- International Society for Traumatic Stress Studies
www.ncvc.org -- National Center for Victims of Crime
www.ncptsd.va.gov -- National Center for Post-Traumatic Stress Disorders
www.rainn.org -- Rape, Abuse, and Incest National Network
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.aabt.org -- Association for Behavioral and Cognitive Therapies
www.ocfoundation.org -- Obsessive Compulsive Foundation

References

Bisson J, Andrew M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2007 Jul 18;(3):CD003388.

Bisson JI. Post-traumatic stress disorder. BMJ. 2007 Apr 14;334(7597):789-93.

Connolly SD, Bernstein GA; Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with anxiety disorders. J Am Acad Child Adolesc Psychiatry. 2007 Feb;46(2):267-83.

Gale C, Davidson O. Generalised anxiety disorder. BMJ. 2007 Mar 17;334(7593):579-81.

Heyman I, Mataix-Cols D, Fineberg NA. Obsessive-compulsive disorder. BMJ. 2006 Aug 26;333(7565):424-9.

Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001848.

Ipser JC, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005473.

Katon WJ. Clinical practice. Panic disorder. N Engl J Med. 2006 Jun 1;354(22):2360-7.

Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul;164(7 Suppl):5-53.

Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007 Mar 6;146(5):317-25.

Saeed SA, Bloch RM, Antonacci DJ. Herbal and dietary supplements for treatment of anxiety disorders. Am Fam Physician. 2007 Aug 15;76(4):549-56.

Schneier FR. Clinical practice. Social anxiety disorder. N Engl J Med. 2006 Sep 7;355(10):1029-36.

Smoller JW, Pollack MH, Wassertheil-Smoller S, et al. Panic attacks and risk of incident cardiovascular events among postmenopausal women in the Women's Health Initiative Observational Study. Arch Gen Psychiatry. 2007 Oct;64(10):1153-60.

A.D.A.M. Copyright

adam.com

Migraine headaches

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Treatment Approaches
Medications Used for Treatm...
Prevention
Medications Used for Preven...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Migraine Surveys

About 17.1% of women and 5.6% of men suffer migraines, according to the 2007 American Migraine Prevalence and Prevention survey. Nearly a third of respondents reported 3 or more migraine attacks per month. Over half were severely impaired or needed bed rest during attacks. Although many patients met the criteria for preventive medication, only a small percentage actually received it.
About 20% of patients with migraine take potentially addictive opioid and barbiturate drugs, even though these drugs have not been approved by the Food and Drug Administration (FDA) for migraine treatment, according to a 2007 survey commissioned by the U.S. National Headache Foundation.

FDA Actions

The opioid drug fentanyl (Fentora) should not be prescribed "off-label" to patients with migraine or other severe headaches, warns the FDA, following several reports of drug-related deaths. Fentanyl is approved only for treating cancer pain.
In 2007, the FDA pulled 15 unapproved ergotamine preparations off the market because they lacked a warning label describing the risks for serious drug interactions.

Migraines in Adolescents

Many adolescents may stop having migraines, or transition to less severe types of headaches, when they reach adulthood, suggests a small 2006 study in Neurology.
Zolmitriptan (Zomig) nasal spray appears to be safe and effective for adolescent migraine, indicates a 2007 study in Pediatrics. Zolmitriptan, like all migraine drugs, is currently approved only for adults.

Sumatriptan-Naproxen Combination

A combination of the triptan drug sumatriptan (Imitrex) and the nonsteroidal anti-inflammatory drug naproxen (Aleve) works better for migraine pain relief than either drug alone, according to a 2007 study in the Journal of the American Medical Association.

Introduction

The pain from a headache does not start from inside the brain. (The brain itself can not feel pain.) Instead, headache pain begins in one or more of the following locations:

The tissues covering the brain
The structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Headache is generally categorized as primary or secondary.

Primary Headache. A headache is considered primary when a disease or other medical condition does not cause it.

Tension headache is the most common primary headache and accounts for 90% of all headaches. [See In-Depth Report # 11: Tension headaches.]
Neurovascular headaches are the second most common primary headaches. This type includes migraines and cluster headaches. [See In-Depth Report # 99: Cluster headaches.] Such headaches are caused by an interaction between blood vessel and nerve abnormalities.

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Over-the-counter pain medications can relieve most headaches.

Click the icon to see a depiction of migraine cause.

Secondary Headache. Secondary headaches are caused by other medical conditions, such as sinusitis, neck injuries or abnormalities, and stroke. About 2% of headaches are secondary headaches caused by abnormalities or infections in the nasal or sinus passages. [See "Causes of Secondary Headaches," in this report.]

It is not uncommon for someone to experience a combination of headache types.

Click the icon to see a comparison of headache symptoms.

Migraine is now recognized as a chronic illness, not simply as a headache. About 28 million people suffer from migraines annually. They are often classified by whether or not auras (seeing bright "spots" or "stars") accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four phases to a migraine (although they may not all occur in every patient): The prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 1 in 5 patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

In some cases, patients eventually experience on-going and chronic headaches. In fact, in an analysis using two different diagnostic methods, between 87 - 90% of daily chronic headaches were actually migraines. Some doctors believe that, unless otherwise demonstrated, any chronic headache consisting of episodes of disabling pain that recur regularly over years should be considered as a migraine.

Chronic migraines may occur from overuse of migraine medications (called a rebound headache) or may develop over time (called transformed migraine).

Rebound Headache. The most common cause of chronic migraine is the rebound effect, which is a cycle caused by overuse of migraine medications. The process involves the following:

Patients typically have taken pain medication for more than 3 days a week on an ongoing basis.
When the patients stop taking medication, they experience a rebound headache.
They start taking the drugs again.
Eventually the headache simply persists, and medications are no longer effective.

Medications implicated in rebound migraines include nonprescription painkillers (acetaminophen, aspirin, ibuprofen), barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.)

Transformed Migraines. In some cases, migraines themselves evolve into chronic, daily headaches called transformed migraines. Such headaches resemble tension headaches but are more likely to be accompanied by gastrointestinal distress and mental or visual disturbances and, in women, to be affected by menstrual cycles. In one study, the risk for transformed migraines were associated with other factors, including allergies, asthma, hypothyroidism, hypertension, and a daily intake of caffeine.

Migraines are defined by the number and length of attacks and whether an aura is present.

Definition of Migraines without Auras (Common Migraine). To be defined as a migraine without aura, a patient should have at least five attacks that have the following characteristics:

A. Each untreated, or unsuccessfully treated, attack must last 4 - 72 hours.

B. It must have at least two of the following four characteristics:

Pain on one side of the head
Pulsing or throbbing pain
Pain severe enough to impair or prevent daily activities
Pain must be intensified by exertion, such as walking up stairs

C. During a headache at least one of the following symptoms must also be present:

Nausea, vomiting or both
Sensitivity to light and noise

In addition, other neurologic or medical conditions that might be causing this pain must be ruled out, or, if they do occur, they are not related in time to the suspected migraine.

Definition of Migraines with Auras (Classic Migraine). To be defined as a migraine with aura, the patients must have at least two attacks that have three out of four of the following events.

At least one fully reversible aura symptom suggesting the headache starts in the cerebral cortex or brain stem.
At least one aura symptom that develops gradually over more than 4 minutes ,or two or more aura symptoms that occur in succession.
No single aura symptom that lasts more than 1 hour. (There may be successive aura symptoms that extend that time, but each one should not last more than 60 minutes.)
The headache itself may begin before, at the same time, or at an interval of no more than an hour after the aura.

As with common migraines, other neurologic or medical conditions that might be causing this pain must be ruled out or if they occur, they are not related in time to the suspected migraine.

Click the icon to see a definition of a migraine.

Although migraine is considered to be a specific chronic illness, it has various presentations that occur in different individuals.

Menstrual Migraines. Migraines are often tied to a woman’s menstrual cycle. Researchers think that estrogen plays a role. About half of women with migraines report an association with menstruation. Compared to migraines that occur at other times of the month, menstrual migraines tend to be more severe, last longer, and not have auras. Triptan drugs can provide relief and may also help prevent these types of migraines.

The highest incidence of migraines typically occurs during the early follicular phase, (beginning of menstruation). A 2005 study found that women are 1.7 times more likely to have a migraine during the 2 days before menstruation begins. But, women are 2.5 times more likely to have a migraine during the first 3 days of menstruation. During this time, migraines are more likely to be severe, with symptoms that include vomiting.

Ophthalmoplegic Migraine. This very rare headache tends to occur in younger adults. The pain centers around one eye and is usually less intense than in a standard migraine. It may be accompanied by vomiting, double vision, a droopy eyelid, and paralysis of eye muscles. Attacks can last from hours to months. A computed tomography (CT) or magnetic resonance imaging (MRI) scan may be needed to rule out an aneurysm (a rupture blood vessel) in the brain.

Retinal Migraine. Symptoms of retinal migraine are short-term blind spots or total blindness in one eye that lasts less than an hour. A headache may precede or occur with the eye symptoms. Sometimes retinal migraines develop without headache. Other eye and neurologic disorders must be ruled out.

Basilar Migraine. Considered a subtype of migraine with aura, this migraine starts in the basilar artery, which forms at the base of the skull. It occurs mainly in young people. Symptoms may include vertigo (the room spins), ringing in the ears, slurred speech, unsteadiness, possibly loss of consciousness, and severe headaches.

Familial Hemiplegic Migraine. This is a very rare inherited genetic migraine disease. It can cause temporary paralysis on one side of the body, vision problems, and vertigo. These symptoms occur about 10 - 90 minutes before the headache.

Status Migrainosus. This is a serious and rare migraine. It is so severe and lasts so long that it requires hospitalization.

About 90% of people seeking help for headaches have a primary headache disorder. The balance of secondary headaches is caused by an underlying disorder that produces the headache as a symptom. Many conditions cause headaches as a symptom. Some of the most common are listed below.

Sinus Headache. Many primary headaches, including migraine, are misdiagnosed as sinus headaches. Nearly 9 in 10 patients who think they have sinus headaches actually have or probably have had a migraine. Sinus headaches occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but telling the difference between these two kinds of headache is difficult, particularly if a headache is the only symptom of sinusitis. The two may even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (Rarely, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headache Due to Neck Problems. Some headaches may be caused by abnormalities of the neck muscles resulting from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck). Nerves in the neck converge in the trigeminal nerve in the face and can generate pain signals that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head, it is usually more severe on one side. The quality of the headache may be similar to an aching tension headache or a mild migraine without aura.

Temporomandibular Joint Dysfunction. Temporomandibular joint dysfunction (TMJ) is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders.

Glaucoma. Acute glaucoma is caused by increased pressure in the eye and requires immediate medical attention. Throbbing pain may be felt around or behind the eyes or in the forehead. Patients have redness in the eye and may see halos or rings around lights.

Brain Tumor. Fear of having a brain tumor is common among people with headaches, but a headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraine or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the two are rarely associated. An exception is malignant hypertension, an uncommon medical emergency, in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Strokes Caused by Blood Clots or Hemorrhages. A blood clot or hemorrhage in the brain leading to a stroke can cause a severe headache, sometimes referred to as a thunderclap headache when it is very sudden and severe. The onset of such a headache, particularly if it is associated with confusion, stupor, or other neurologic symptoms, mandates prompt medical attention. It is important to determine if a clot or bleeding is causing the stroke, since treatments are very different.

Head Injuries. It is obvious that a significant blow to the head will cause pain. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. In very rare instances, ordinary physical strain may injure or weaken the meninges, causing a leakage of cerebrovascular fluid (the fluid that bathes the brain). This can cause severe headache and nausea, which are relieved by lying flat. The condition is very treatable. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Gynecologic Problems. Many clinicians have anecdotally linked gynecologic problems, such as ovarian cysts and menstrual disorders, to chronic headaches, and new data are emerging to support this association.

Temporal (Giant Cell) Arteritis. Certain causes of headaches are unique to the elderly, such as temporal arteritis, also called giant cell arteritis. Inflammation in arteries that carry blood to the head, neck, and sometimes the upper part of the body can cause very severe headaches. The risk for this headache is highest in people over age 70, especially among women, people of European heritage, and patients with polymyalgia rheumatica.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain. (It may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing.) Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Click the icon to see an image of the sinuses.

Prognosis

For many people, migraines eventually go into remission and sometimes disappear completely, particularly as they age. Estrogen decline after menopause may be responsible for remission in some older women. One study reported that the following people with migraines (called migraineurs) have a better chance of remission if they have:

A family history of migraine with aura
Migraines that are not triggered by light
No other primary headaches

According to another study, a history of head trauma or oral contraceptive use predicted a poorer long-term outlook.

Migraine or severe headache is a risk factor for stroke in both men and women, especially before age 50. About 19% of all strokes occur in people with a history of migraine. Research indicates that migraine also increases the risk for other types of heart problems.

Migraine with aura carries a higher risk for stroke than without auras. A 2005 analysis of over 12,000 participants from an atherosclerosis risk study found that migraine with aura was significantly associated with higher risk for stroke and transient ischemic attacks. Another 2005 study suggested that people who experience migraine with aura tend to have more cardiovascular risk factors than people without migraine. These risk factors included worse cholesterol profile, higher blood pressure, early history of heart disease and stroke, and greater likelihood of using oral contraceptives.

Results from a 2005 study showed that women who have migraine with aura are at increased risk of ischemic stroke compared with those who do not have auras and those who have non-migraine headaches. Women under age 55 had the highest risk, with more than double the risk. A 2006 Women’s Health Study of women ages 45 and older found that migraine with aura also increases women’s risk for heart attack, angina, and death due to ischemic heart disease (in which blood flow is decreased due to narrowing of coronary arteries). Migraine without aura did not increase heart disease and stroke risks.

Studies suggest specific stroke risk factors for younger women with migraines, particularly those with auras. Smoking, high blood pressure, and birth control pills considerably raise one's risk 10 - 20 times.

Researchers are also studying the relationship between patent foramen ovale (PFO) and migraine. A PFO is a hole in the wall dividing the upper left and right heart chambers. About half of patients with PFO have severe migraines with aura. Researchers are investigating whether surgical repair of the PFO may help control migraines in patients with this heart condition.

Migraine and other headaches associated with aura may increase the risk for retina damage (retinopathy) among middle-aged people, suggests a 2007 study.

The negative impact of migraines on quality of life, families, and even work productivity is significant and often underrated as a serious complication. Studies indicate that people with migraines have poorer social interactions and emotional health than patients with chronic medical illnesses, including asthma, diabetes, and arthritis. Anxiety (particularly panic disorders) and major depression are also strongly associated with migraines.

A 2005 National Headache Foundation-sponsored survey of migraine sufferers reported that:

90% of people with migraines could not function normally on the day of a migraine attack
80% experienced abnormal sensitivity to light and noise
75% experienced nausea and vomiting
30% required bed rest
25% missed at least 1 day of work due to migraine in past 3 months

Effect of Pregnancy on Migraines. In one study, pregnant women with tension or migraine headaches experienced 80% fewer headaches, usually after the end of the first trimester.

Effect of Migraine on the Pregnant Woman or Fetus. Migraine headaches do not pose any added risks during pregnancy to the mother or the fetus, although women with migraines may be at higher risk for having smaller (but not premature) babies.

Causes

Until recently, the general theory on the migraine process rested solely on the idea that abnormalities of blood vessel (vascular) systems in the head were responsible for migraines. Now, however, doctors tend to believe that migraine starts with an underlying central nervous system disorder. When triggered by various stimuli, this disorder sets off a chain of neurologic and biochemical events, some of which subsequently affect the brain's vascular system. No experimental model fully explains the migraine process.

There is certainly a strong genetic component in migraine with or without auras. Researchers have located a single genetic mutation responsible for the very rare familial hemiplegic migraine, but several genes are likely to be involved in the great majority of migraine cases. Numerous chemicals, structures, nerve pathways, and other players involved in the process are under investigation.

Central Nervous Disorder. One theory that attempts to integrate many of the known events in the migraine process is as follows:

Stress or some unknown factor triggers the release of certain protein fragments called peptides (Substance P, calcitonin gene-related peptide, and others).
These peptides dilate blood vessels and produce an inflammatory response that triggers over-excitation of the nerve cells in the trigeminal pathway. [This nerve pathway runs from the brain stem to the head and face. These nerves spread to the meninges (the membrane covering of the brain).]
While the brain itself is insensitive to pain, the meninges and blood vessels around the brain are sensitive to pain. Some doctors suggest that pain occurs when blood drains from the center of the head to the blood vessels around the brain.
Auras are believed to be a response to blood flow changes that cause a rapid reduction in brain activity that reaches the cerebral cortex (the outer layer of the brain), referred to as spreading depression. This effect may be visualized as an electrical wave spreading through the brain just as a wave of water is caused by the dropping of a pebble. Some research suggests that in people with auras, the cortical spreading depression itself activates the inflammation in the trigeminal nerves that triggers pain in the meninges.

One theory of the cause of migraine is a central nervous system (CNS) disorder. The CNS consists of the brain and spinal cord. In migraine, various stimuli may cause a series of neurologic and biochemical events that affect the brain's vascular system.

Abnormal Calcium Channels. Some migraines may be due to abnormalities in the channels within cells that transport the electrical ions calcium, magnesium, sodium, and potassium. Calcium channels appear to play a particularly critical role in migraine:

Calcium channels regulate the release of serotonin, an important neurotransmitter in the migraine process. (A neurotransmitter is a chemical messenger that allows communication between nerves in the brain.)
Magnesium interacts with calcium channels, and magnesium deficiencies have been detected in the brains of patients with migraine.
Calcium channels also play a major role in cortical spreading depression, the brain event that appears to be important in migraine symptoms.

Some patients with migraines may inherit one or more factors that impair calcium channels, making them susceptible to headaches. For example, mutations in a gene that encodes calcium channels appears to be responsible for familial hemiplegic migraine.

Researchers are also investigating factors that are common to both migraines and tension-type headaches. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Serotonin and Other Neurotransmitter Levels. Neurotransmitters are chemical messengers in the brain. Serotonin is a neurotransmitter (chemical messenger in the brain) that is important for sleep, well-being, and other factors that affect quality of life. Abnormalities in serotonin levels have been observed in both tension-type and migraine headache sufferers. Altered levels of other neurotransmitters, importantly dopamine and stress hormones, also occur with migraine and tension-type headaches.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people over-sensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Reduced Magnesium Levels. Magnesium deficiencies have been observed in people with both tension-type and migraine headaches. Researchers have noted a drop in magnesium levels before or during a migraine attack. Magnesium plays a role in nerve cell function. Reduced levels could be a destabilizing factor, causing the nerves in the brain to misfire, possibly even accounting for the auras that many sufferers experience.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger that may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are slightly more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Inflammation in the Maxillary Nerve. Early studies suggest that some chronic tension-type and migraine headaches may be caused by inflammation in the nerve that runs behind the cheekbone (the maxillary nerve) -- not around the covering of the brain. In fact, some work using ice water for reducing swelling in areas of the gums above the last upper molars has relieved some severe migraine and tension-type headaches.

A wide range of events and conditions can alter conditions in the brain that bring on nerve excitation and trigger migraines. They include, but are not limited to:

Emotional stress
Intense physical exertion (exercise, lifting, and even bowel movements or sexual activity)
Abrupt weather changes
Bright or flickering lights
High altitude
Travel motion
Lack of sleep
Low blood sugar and fasting
Chemicals found in certain foods. More than 100 foods may potentially trigger migraine headache. Caffeine is one such trigger. Caffeine withdrawal can also trigger migraines in people who are accustomed to caffeine. Experts recommend that patients keep a headache diary to track which foods trigger migraine.

Risk Factors

About 30 million Americans suffer from migraine headaches. They affect about 17% of all women and 6% of men. In fact, 70% of all migraine sufferers are women. Migraine is more prevalent among women throughout the world and in every culture. Although the incidence of migraine is similar for boys and girls during childhood, it increases in girls after puberty. Most people with migraine have 1 - 4 attacks per month.

Hormone Fluctuations in Women. Most migraines in women develop during the hormonally active years between adolescence and menopause. Fluctuations of estrogen and progesterone, rather than their presence, appear to increase the risk for migraines and their severity in some women.

About half of women with migraines report headaches associated with their menstrual cycle, although true menstrual migraines may actually be less common. True menstrual migraines tend not to have auras and to increase in prevalence between 2 days before and 5 days after the onset of period.
The first 3 months of pregnancy can worsen migraines in some women, although one study reported that pregnancy had little effect one way or the other on severity in most women with chronic headaches.
Women whose migraines are affected by pregnancy or menstruation are also likely to have worse migraines if they take oral contraceptives or hormone replacement therapies.

General Age of Onset. More than 20% of adults with migraines report that their headaches started before age 10, and over 45% say they started before age 20. The incidence of migraine declines in both men and women after age 40.

Migraine in Children. Migraine headaches occur in all ages and can appear in children as young as 4 years of age. Migraines in children are equally prevalent in boys and girls. Studies estimate that about 4 – 10% of all children suffer from migraine. Research indicates that overweight children may be especially susceptible to headaches, although this association is most likely due to poor nutrition and lack of exercise rather than excess weight. Children who have sleep problems, especially difficulty falling asleep, may also be more prone to migraines.

A small 2006 study indicated that some adolescents with migraine may eventually grow out of their condition. By the end of the 10-year study, 38% of patients had stopped having migraines, and 20% had transitioned into less severe tension-type headache. Children with a family history of migraine were more likely to continue having migraines.

Migraine Onset in Older Adults. Although uncommon, late-life migraine occurs in about 1% of the population, usually in men. In such cases, it often occurs as migraine with visual disturbances but without headache.

Migraine headaches can be inherited. If both parents suffer from migraines, their children have a 75% chance of getting them. When only one parent gets migraines, there is a 50% chance that children will be afflicted.

Caucasians have a higher risk than either African-Americans or Asians. Worldwide, one study reported that migraines are most common in North America. They are slightly less prevalent in South America and Europe and far less common in Asia and Africa. Investigators believe that the differences are due to genetic variations, not lifestyle factors.

People with migraine have a higher incidence of other medical conditions, including:

Asthma and allergies. These conditions have also been associated with a higher risk for conversion from having periodic migraines attacks to a chronic form (transformed migraines).
H. pylori infection. People who are infected with the bacteria H. pylori, the major cause of peptic ulcers, are at higher risk for migraines.
Epilepsy. Patients with epilepsy are twice as likely to have migraines as the general population.
Fibromyalgia
Systemic lupus erythematosus
Raynaud syndrome
Mitral valve prolapse
Narcolepsy

One study suggested that women with migraines tend to over-respond to stressful situations. In the study, they were more likely than other women to be diligent, conscientious, and overly sensitive to pressure from others. More likely, however, a person's family history of migraine, rather than any personality trait, is the important risk factor.

Diagnosis

Anyone, including children, who has recurring or persistent headaches should consult a doctor. There are no blood tests or imaging techniques that can be used to diagnose migraine headaches. A diagnosis will be made on the basis of history and physical exam, and, if necessary, tests may be necessary to rule out other diseases or conditions that may be causing the headaches. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting
Behaviors during a headache. This may help distinguish between migraine and tension headaches. The predominant behavior with tension headaches is massaging the scalp, temples, or the nape of the neck. A person with migraines is more apt to use compression (such as tying a scarf around the forehead and temples) or to apply cold. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The presence of auras or other visual disturbances do not always identify migraine:

Patients with severe sinus infections may experience double vision or visual loss. (This is an emergency condition, since it indicates the infection has spread to areas around the eyes.)
Many migraine sufferers have no auras.
Many elderly people with late-onset migraine have auras but no pain.

Note all conditions, including any foods eaten, preceding an attack. Often two or more triggers interact to produce a headache. For example, a combination of weather changes and fatigue can make headaches more likely than the presence of just one of these events.
Keep a migraine record for at least three menstrual cycles. For women, this can help to confirm or refute a diagnosis of menstrual migraine.
Track medications. This is important for identifying possible rebound headache or transformed migraine.
Attempt to define the intensity of the headache using a number system, such as:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
Any uncharacteristic dietary changes
Any current medications or recent withdrawals from any drugs, including over-the-counter or natural remedies.
Any history of caffeine, alcohol, or drug abuse.
Any serious stress, depression, and anxiety.

The doctor will also need a general medical and family history of headaches or diseases, such as epilepsy, that may increase their risk. Migraine tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor may ask questions to test short-term memory and related aspects of mental function.

Diagnosing the cause of persistent daily headache is difficult, even for expert doctors. Studies report that people who visit the emergency room with disabling headache are often misdiagnosed as tension-type headaches instead of migraines. It is important to choose a doctor who is sensitive to the needs of headache sufferers and aware of the latest advances in treatment.

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

Differentiating Rebound Headaches from Transformed Migraines. Migraines that evolve to chronic headaches must be first differentiated between natural transformed migraines and rebound headaches (the most common cause of persistent migraines):

A transformed migraine is usually more consistent in its severity and its location than a rebound headache.
Transformed migraines are less sensitive to triggers than rebound headaches.

Differentiating Transformed from Tension Headaches. Once rebound headache is ruled out, the doctor must then differentiate natural transformed migraines from tension headaches:

In most cases of transformed migraine (but not tension headache), gastrointestinal or neurologic symptoms are present.
Transformed migraine is also frequently associated with menstrual fluctuations in women.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headaches that wake them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headaches.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other imaging tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, positron emission tomography (PET), and single-photon emission computed tomography (SPECT). These tests are only performed if there is reason to suspect an underlying disease or as part of clinical studies.

A CT (computed tomography) scan is a much more sensitive imaging technique than x-ray, allowing high definition of not only the bony structures but also the soft tissues. Clear images of organs and structures, such as the brain, muscles, joints, veins and arteries, as well as of tumors and hemorrhages, may be obtained with or without the injection of contrasting dye.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition by believing it to be one of their usual headaches. Such patients should call a doctor promptly if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Treatment Approaches

Many effective headache remedies are available for treating a migraine attack. Still, a study that analyzed over 800,000 cases of migraine reported that most migraines are not treated according to any recommended guidelines. In the study, 30% of patients were treated with potentially addictive opioids -- most often merepidine (Demerol). Furthermore, 70% of these patients were not offered effective and available anti-migraine drugs. Anti-nausea drugs that have no effect on headaches were used six times more often than drugs that reduce headaches.

A 2007 survey of migraine sufferers, commissioned by the U.S. National Headache Foundation, reported that 20% of patients are prescribed non-approved medications containing opioids or barbiturates. The survey also indicated that patients who take non-approved drugs are more likely to experience drug-related side effects. For mild migraines, non-prescription treatments (Excedrin Migraine, Advil Migraine, Motrin Migraine Pain) are the best first choice. For severe migraines, doctors recommend starting with a triptan drug.

Preventive treatment, used to stop migraine attacks before they happen, may help many patients. According to another 2007 survey, more than 1 in 4 patients with migraine are candidates for preventive therapy but most do not receive it.

As many as 30% of patients with migraine also have accompanying headaches resulting from tension, drugs, infections, or other causes. It is important to distinguish between headache types in order to determine appropriate treatment.

General Guidelines. The general goals of treatment are:

Choose drugs with as few side effects as possible. Patients should talk to their doctors about various methods for administering the medication (pills, injections, nasal spray, or rectal suppositories) and begin with the one they believe will be the least distressing.
Treat the attack rapidly, within an hour of symptom onset if possible. Start with low doses, and build up dosage slowly.
Try to minimize the use of back-up or "rescue medications." (A rescue medication is typically a narcotic opiate drug, which is used for pain relief when other medications fail.)
Try to guard against rebound effect. Nearly all drugs used for migraine can cause rebound headache, and patients should not take any the drugs for longer than 2 days per week.
It may take 2 - 4 months for any drug to be effective.

Stepped-Up Treatment Approach. Some doctors recommend a stepped-up treatment course for an acute migraine attack. This involves starting with the least potent treatments and taking increasingly more powerful drugs until the pain stops. In this approach, patients may need up to five different medications to achieve pain relief. A typical stepped-up approach is the following:

The patient should first use nonprescription pain relievers (NSAIDs, Excedrin Migraine) and stress-reduction techniques.
If these are not effective within 2 hours, the patient should take migraine-specific drugs. Triptans are the first choice, then ergot derivatives.
Patients with migraines associated with severe nausea or vomiting may use injected or rectally administered drugs. Nausea itself should be treated with specific anti-nausea drugs, such as metoclopramide (Reglan).
If migraine medications fail to relieve symptoms within 4 hours, rescue drugs (opioids, corticosteroids) may be used.

Stratified Approach. Many doctors and patients now prefer the stratified approach. The doctor first estimates the severity of the patient's condition based on his or her history. Then, depending on the severity of a typical attack, the doctor decides whether the patient should start with more or less powerful drugs at the first signs of the migraine:

Patients with less disabling migraines start with general pain relievers.
Patients with a history of moderate-to-severe migraines start with migraine-specific prescription medicine, such as a triptan, at the onset of mild pain.

Some studies report dramatic relief with the stratified approach. In one study, zolmitriptan, a newer triptan, reduced the intensity of headaches within 2 hours in 70% of patients with moderate pain but only in 44% of those with severe headaches.

Side effects can be severe with many migraine drugs, although newer drugs, such as the recent generation triptans, may provide effective early relief without significant side effects.

Studies estimate that between 5 - 10% of children have migraines but that the disorder is underdiagnosed in children. An interesting study reported that when children drew pictures in response to their doctors' questions about their migraines, the doctors were able to tell the difference between migraine and non-migraine headaches in the majority of cases.

Symptoms in Children. The standard diagnostic criteria for migraine in adults may apply to only about two-thirds of migraines in children and adolescents. For example, doctors have seen the following differences:

Headaches tend to last for a shorter time (as little as an hour) in children.
Migraine pain tends to occur in the face and on both sides of the head in two-thirds of child patients.
Children often have a form of migraine known as a migraine equivalent or abdominal migraine, which does not cause a headache at all. Instead, children experience periodic bouts of nausea and vomiting (called cyclic vomiting syndrome) or other secondary symptoms found in adult migraine, such as a reaction against light or sound. Cyclic vomiting may occur in nearly 2% of school-aged children with or without a migraine association.
Migraine triggers in children are similar to those in adults, but common ones in children are anxiety and fear, and eating ice cream.

Outlook in Children. Migraine in children is disabling, as it is in adults, and they tend to lose more school days than other children. Children with frequent headaches may also be at higher risk for headaches in adulthood and also for other physical and psychiatric problems. However, some children who have migraine eventually stop having attacks when they reach adulthood, or have less severe types of headaches.

Treatments in Children. Most children with migraines may need only mild pain relievers and home remedies (such as ginger tea) to treat their headaches. The American Academy of Neurology’s 2004 practice guidelines for children and adolescents recommend the following drug treatments:

For children age 6 years and older, ibuprofen (Advil) is recommended. Acetaminophen (Tylenol) may also be effective. Acetaminophen works faster than ibuprofen, but the effects of ibuprofen last longer.
For adolescents age 12 years and older, sumaptriptan (Imitrex) nasal spray is recommended.

Preventive Measures in Children. Non-medication methods, including biofeedback and muscle relaxation techniques may be helpful. In one study of children with migraines and poor sleep habits, who were taught how to sleep better instructions without using medications had significantly fewer migraine attacks.

If these methods fail, then preventive drugs may be used, although evidence is weak on the effectiveness of standard migraine preventive drugs in children.

If medication overuse causes rebound migraines develop, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may need only to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient can usually stop abruptly or gradually. The patient should expect the following:

Most headache drugs can be stopped abruptly, but the patient should talk to their doctor first. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days.
The patient may take other pain medicines during the first days. Examples of drugs that may be used include dihydroergotamine (with or without metoclopramide), NSAIDs (in mild cases), corticosteroids, or valproate.
The patient must expect their headache to get worse after they stop taking their medications, no matter which method they use. Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).
If the symptoms do not respond to treatment and cause severe nausea and vomiting, the patient may need to be hospitalized.

On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward, and one study reported that 82% of patients significantly improved 4 months after medication withdrawal.

Medications Used for Treatment

Many different medications are used to treat migraines. However, the Food and Drug Administration (FDA) has specifically approved only the following types of drugs for migraine treatment:

Non-prescription drugs: Excedrin Migraine, Advil Migraine, Motrin Migraine Pain
Prescription drugs: Triptans and ergotamine

Other types of drugs, including opioids and barbiturates, are sometimes prescribed off-label for migraine treatment. Opioids and barbiturates have not been approved by the FDA for migraine relief, and they can be addictive.

All FDA-approved migraine treatments are approved only for adults. No migraine products have officially been approved for use in children.

Some patients with mild migraines respond well to over-the-counter (OTC) painkillers, particularly if they take the medicine at the very first sign of an attack.

The Food and Drug Administration has approved three OTC (nonprescription) products to treat migraine. Excedrin Migraine (a combination of aspirin, acetaminophen, and caffeine) was the first such medication approved for the temporary relieve of migraine and its symptoms. Studies have reported significant relief in nearly 70% of patients. It may also help menstrual migraines. Advil Migraine and Motrin Migraine Pain, both containing ibuprofen, are also approved to treat migraine headache.

Cooling Pads. Cooling pads may help during an attack. Some products (Migraine Ice, TheraPatch Headache Cool Gel) use a pad containing a gel that cools the skin for up to 4 hours and can be placed on the forehead, temple, or back of the neck.

Non-steroidal anti-inflammatory drugs (NSAIDs) include aspirin, ibuprofen, and naproxen. They were among the first types of drugs tried to treat mild-to-moderate migraines. Aspirin, ibuprofen (Advil, Motrin), and naproxen (Anaprox, Aleve) are all available without prescription. Naproxen may have specific benefits for migraine. A 2007 study indicated that a combination of naproxen and sumatriptan provides better migraine pain relief than either drug alone.

Other types of NSAIDs are available only by prescription. Some studies indicate that the NSAID combination diclofenac-potassium (Cataflam) may work faster than the migraine drug sumatriptan (Imitrex) and help reduce nausea. The combination is not appropriate for people allergic to aspirin or at risk for bleeding.

Injectable NSAIDs, particularly ketorolac (Toradol), may be very effective for severe and persistent migraines. A 2003 study found that intravenous ketorolac provided greater pain relief than nasal sumatriptan (Imitrex). A 2005 study presented at the annual meeting of the American Headache Society reported that intravenous ketorolac was more effective than opioid drugs for late-stage treatment of severe migraine attacks.

COX-2s are a class of prescription drugs that have the anti-inflammatory effects of NSAIDs, but do not upset most people's stomachs. However, most of these drugs have been withdrawn from the U.S. market due to increased risk for heart attack and stroke. Celecoxib (Celebrex) is the only available COX-2, and it has a strong warning label alerting users of the potential for heart attack, stroke, and serious gastrointestinal problems. (The warning is the same one the Food and Drug Administration recommended for the labels of prescription NSAIDs in 2005.)

NSAID Side Effects. High dosages and long-term use of NSAIDs can increase the risk for heart problems, kidney problems, and stomach bleeding. In April 2005, the FDA asked drug manufacturers of prescription NSAIDs to include with their products the same boxed warning used for the COX-2 inhibitor celecoxib (Celebrex). This boxed warning emphasizes an increased risk for cardiovascular events and gastrointestinal bleeding in people taking these drugs. The FDA also requested manufacturers of over-the-counter NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions.

Triptans (also referred to as serotonin agonists) were the first drugs specifically developed for use against migraine. They are the most important migraine drugs currently available. They help maintain serotonin levels in the brain, and so specifically target one of the major components in the migraine process.

Triptans are recommended as first-line drugs for adult patients with moderate-to-severe migraines when NSAIDs are not effective. Triptans have the following benefits:

They are effective for most patients with migraine, as well as patients with combination tension and migraine headaches.
They do not have the sedative effect of other migraine drugs.
Withdrawal after overuse appears to be shorter and less severe than with other migraine medications

Sumatriptan. Sumatriptan (Imitrex) has the longest track record and is the most studied of all triptans. It is available as a fast-dissolving pill, nasal spray, or injection. Injected sumatriptan works the fastest of all the triptans and is the most effective, but it can cause pain at the injection site. The nasal spray form bypasses the stomach and is absorbed more quickly than the oral form. Some patients report relief as soon as 15 minutes after administration. The spray tends to work less well when a person has nasal congestion from cold or allergy. It may also leave a bad taste. Sumatriptan is effective for many patients, but headache recurs in 20 - 40% of people within 24 hours after taking the drug.

A 2007 study in the Journal of the American Medical Association suggested that a combination of sumatriptan and naproxen works better than either drug alone.

Other Triptans. Newer triptans include almotriptan (Axert), zolmitriptan (Zomig), naratriptan (Amerge), rizatriptan (Maxalt), frovatriptan (Frova), and eletriptan (Relpax). Comparison studies with sumatriptan suggest that some of the newer drugs have fewer side effects and are superior to sumatriptan for providing immediate, sustained, and consistent pain relief. Recurrence rates are also lower. They are also being investigated for prevention under certain circumstances, such as menstrual migraines, but benefits appear limited.

Studies on newer triptans indicate:

Almotriptan is as effective as oral sumatriptan and may have fewer side effects, particularly chest pain, than most other triptans.
Rizatriptan may have the most rapid effects of all oral triptans. Zolmitriptan also has a more rapid effect than sumatriptan (although there appears to be no significant difference in adverse effects). Both rizatriptan and zolmitriptan are also available as rapidly dissolving wafers.
Eleptriptan is also very rapidly effective at high doses, but at those levels may have significant adverse effects. (To date, it does not seem to have any advantages over other triptans in head-to-head comparisons.)
Naratriptan and frovatriptan have a delayed response but long duration, few side effects, and lower risk for recurrence than with sumatriptan. Some evidence suggests that they may have specific benefits for stopping prolonged migraines and may even play a role in prevention.
Frovatriptan: A large study of more than 500 women with an average 12-year history of menstrual migraines examined the use of frovatriptan for the short-term prevention of such headaches. Researchers found that the migraines disappeared in over half of the women on the higher dose (5 mg) of frovatriptan.
Zolmitriptan (Zomig): Several studies indicate that zomitriptan nasal spray may be safe and effective for adolescents. In one study, zolmitriptan relieved pain within 2 hours for nearly half of the children (aged 12 - 17 years) enrolled in the trial. Zolmitriptan nasal spray is approved only for adults.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, can include:

Tingling and numbness in the toes
Sensations of warmth
Discomfort in the ear, nose, and throat
Nausea
Drowsiness
Dizziness
Muscle weakness
Heaviness, pain, or both in the chest. (About 40% of patients taking sumatriptan experience these symptoms, and they are major factors in discontinuing the drug. Newer drugs, such as almotriptan, produce fewer chest symptoms.)
Rapid heart rate

Complications of Triptans. The following are potentially serious problems.

Complications of heart and circulation. Triptans narrow (constrict) blood vessels. Because of this effect, spasms in the blood vessels may occur and cause serious side effects, including stroke and heart attack. Such events are rare, but patients with an existing history or risk factors for these conditions should generally avoid triptans.
Serotonin syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptan drugs used to treat migraine, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) -- such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) -- and selective serotonin/norepinephrine reuptake inhibitors (SNRIs), such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with a SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following people should avoid triptans or take them with caution and only with the advisement of a doctor:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Children and adolescents. They may be safe, but controlled studies are needed to confirm this. (Triptans should not, in any case, be the first-line treatment for children.)
People with basilar or hemiplegic migraines. (Triptans are not indicated for these migraineurs.)
There is no evidence to date of any higher risk for birth defects in pregnant women who take triptans. Still, women should be cautious about taking any medications during pregnancy and discuss any possible adverse effects with their doctors.

Drugs containing ergotamine (commonly called ergots) constrict smooth muscles, including those in blood vessels, and are useful for migraine. They were the first anti-migraine drugs available. Ergotamine is available by prescription in the following preparations:

Dihydroergotamine (DHE) is an ergot derivative. It is administered as a nasal spray form (Migranal) or by injection, which can be performed at home.
Ergotamine is available tablets taken by mouth, tablets taken under the tongue (sublingual), and rectal suppositories. Some of the tablet forms of ergotamine contain caffeine.

Ergotamine’s role since the introduction of triptans is now less certain. Only the rectal forms of ergotamine are superior to rectal triptans. Injected, oral, and nasal-spray forms are all inferior to the triptans. Ergotamine may still be helpful for patients with status migrainous or those with frequent recurring headaches.

Side Effects. Side effects of ergotamine include:

Nausea
Dizziness
Tingling sensations
Muscle cramps
Chest or abdominal pain

The following are potentially serious problems:

Toxicity. Ergotamine is toxic at high levels.
Adverse effects on blood vessels. Ergot can cause persistent blood vessel contractions, which may pose a danger for people with heart disease or risk factors for heart attack or stroke.

Internal scarring (fibrosis). Scarring can occur in the areas around the lungs, heart, or kidneys. It is often reversible if the drug is stopped.

The following patients should avoid ergots:

Pregnant women. Ergots can cause miscarriage.
People over age 60.
Patients with serious, chronic health problems, particularly those of the heart and circulation.

Ergotamine can interact with other medications, such as antifungal drugs and some antibiotics. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label. The five FDA-approved ergotamine products that remain on the market are:

Migergot suppository (marketed by G and W Labs)
Ergotamine Tartrate and Caffeine tablets (marketed by Mikart and West Ward)
Cafergot tablets (marketed by Sandoz)
Ergomar sublingual tablets (marketed by Rosedale Therapeutics)

Nasal drops containing lidocaine, a local anesthetic, can provide effective and quick pain relief within 15 minutes for many migraine sufferers. However, lidocaine has certain downsides:

It is rather difficult to administer. Patients must be lying down with their head dangling.
The headache often relapses in an hour, and other drugs must then be used.
Side effects include unpleasant taste, burning sensation, and facial numbness.

However, the drug does not cause drowsiness or heart rhythm disturbances as some other migraine treatments do. It should not be used for any other form of headache.

If the pain is very severe and does respond to other drugs, doctors may try painkillers containing opioids. Opioid drugs include morphine, codeine, meperidine (Demerol), and oxycodone (Oxycontin)]. Butorphanol is an opioid in nasal spray form that may be useful as a rescue treatment when others fail.

Opioids are not approved for migraine treatment and should not be used as first-line therapy. Nevertheless, many opioid products are prescribed to patients with migraine, sometimes with dangerous results. In 2007, following reports of several drug-related deaths, the Food and Drug Administration warned that the cancer pain pill fentanyl (Fentora) should not be used to treat patients with migraine or others conditions for which the drug is not specifically approved.

Side Effects. Side effects for all opioids include drowsiness, impaired judgment, nausea, and constipation. There is a risk for addiction, and these drugs can become ineffective with long-term use for chronic migraines. Doctors should not prescribe opioids to patients at risk for drug abuse, including those with personality or psychiatric disorders.

Metoclopramide (Reglan) is used in combinations with other drugs to treat the nausea and vomiting that occurs with other drugs and with migraine itself. Metoclopramide and other anti-nausea drugs, such as domperidone (Motilium), may help the intestine better absorb migraine medications.

New drugs in clinical trials include tonabersat (a gap junction blocker), trexima (a combination triptan and non-steroidal anti-inflammatory drug), GW274150 (a nitric oxide synthase inhibitor), and MK-0974 (a calcitonin gene-related peptide antagonist). Researchers are also investigating a nasal spray containing capsaicin, the chemical found in cayenne peppers.

Prevention

There are several ways to prevent migraine attacks. You should try a healthy diet, the right amount of sleep, and non-drug approaches, such as biofeedback, first for prevention.

Behavioral techniques that reduce stress and empower the patient may help some people with migraines. Studies report between 35 - 50% reduction in migraine and tension-type headaches with these approaches. They generally include:

Biofeedback therapy
Cognitive-behavioral therapy
Relaxation techniques

Behavioral methods may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. They may be particularly beneficial for children, adolescents, and pregnant and nursing women, and anyone who cannot take most migraine medications.

Biofeedback. Studies have demonstrated some effectiveness from biofeedback for migraine headaches. Biofeedback training teaches the patient to monitor and modify physical responses, such as muscle tension, using special instruments for feedback.

Cognitive Behavioral Therapy. Behavioral therapy may be useful alone but is particularly beneficial for patients who are on preventive drug treatments. It typically uses the headache diary to track activities and headaches. The patient then works with the therapist to change or add behaviors or medications that will reduce the frequency and severity of attacks.

Alternative non-drug therapies used for headache management and prevention include hypnosis, meditation, visualization and guided imagery, acupuncture, acupressure, yoga, and other relaxation exercises. There is no clear evidence that any of these techniques have specific value for migraines.

Some studies report the following:

Acupuncture. Acupuncture is a Chinese medicine technique that uses thin needles to stimulate specific points aligned with energy pathways in the body. Studies have showed mixed results on the benefits of acupuncture for migraine. A 2005 study published in the Journal of the American Medical Association reported that acupuncture was no more effective than sham acupuncture (needles placed at non-acupuncture points) in preventing migraines. More than 300 people were enrolled in this randomized trial. A 2006 study of 960 people, published in Lancet Neurology, found that real acupuncture, sham acupuncture, and standard drug treatment were all equally effective in preventing migraine attacks.
Relaxation Techniques. Muscle relaxation techniques may be helpful. One study reported that relaxation treatments appeared to help adolescents with migraine but not tension headaches.

Hormonal drugs, such as oral contraceptives or hormone replacement therapy, have a mixed effect on women with migraines. Oral contraceptives have been associated with worse headaches in 18 - 50% of women and have also been linked to a higher risk for stroke in women with classic migraines (with auras). Young women should avoid or stop oral contraception if they have classic migraines, migraines that worsen or change character after oral contraceptives , if they have close relatives with stroke or heart disease, or if they smoke.

Some evidence suggests, however, that oral contraceptives may help prevent true menstrual migraines (which do not have auras). In such cases, their benefits may outweigh the low risk of a serious adverse event. Keeping a migraine record for at least three menstrual cycles can help confirm whether a woman actually has a true menstrual migraine.

Making a few minor changes in your lifestyle can make your migraines more bearable. Improving sleep habits is important for everyone, and especially those with headaches. What you eat also has a huge impact on migraines, so dietary changes can be extremely beneficial, too.

Avoiding Food Triggers. Avoiding foods that trigger migraine is an important preventive measure. Common food triggers include monosodium glutamate (MSG), processed lunch meats that contain nitrates, dried fruits that contain sulfites, aged cheese, alcohol and red wine, chocolate, and caffeine. However, people’s responses to triggers differ. Keeping a headache diary that tracks diet and headache onset can help identify individual food triggers.

Healthy Diet. One study indicated that a diet low in fat and high in complex carbohydrates may significantly reduce the frequency, severity, and duration of migraine headaches. Such a diet is healthy in general, in any case.

Eating Regularly. Eating regularly is important to prevent low blood sugar. People with migraines who fast periodically for religious reasons might consider taking preventive medications.

Fish Oil. Some studies suggest that omega-3 fatty acids, which are found in fish oil, have anti-inflammatory and nerve protecting actions. These fatty acids can be found in oily fish, such as salmon, mackerel, or sardines. They can also be obtained in supplements of specific omega-3 compounds (DHA-EPA).

Exercise is certainly helpful for relieving stress. An analysis of several studies reported that aerobic exercise in particular might help prevent migraines. It is important, however, to warm up gradually before beginning a session, since sudden, vigorous exercise might actually precipitate or aggravate a migraine attack.

Manufacturers of herbal remedies and dietary supplements do not need Food and Drug Administration 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. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Riboflavin (Vitamin B2). There is reasonable evidence on the benefits of vitamin B2 for migraine sufferers. In one study, patients who took 400 mg of vitamin B2 (riboflavin) reduced their migraine attacks by half, although the vitamin had no effect on the severity or duration of migraines that did occur. In another study, it helped increase the effectiveness of beta-blockers, drugs used to prevent migraines in some people. Vitamin B2 is generally safe, although some people taking high doses develop diarrhea.

Magnesium Supplements. Studies have reported a higher rate of magnesium deficiencies in some patients with migraine, such as those with menstrual migraines. Magnesium helps relax blood vessels. Some patients report relief from supplements.

Feverfew. Feverfew is the most studied herbal remedy for headaches and is effective in some cases. However, like all effective headache remedies, overuse can cause a rebound effect.

Ginger. In general, herbal medicines should never be used by children or pregnant or nursing women without medical counsel. One exception may be ginger, which has no side effects and can be eaten in powder or fresh form, as long as quantities are not excessive. Some people have reported less pain and frequency of migraines while taking ginger, and children can take it without danger.

Medications Used for Prevention

The Food and Drug Administration has approved four drugs for prevention of migraine:

Propanolol (Inderal)
Timolol (Blacadrene)
Divalproex sodium (Depakote)
Topiramate (Topamax)

Propanolol and timolol are beta-blocker drugs. Divalproex and topiramate are anti-seizure drugs. Many other drugs are also being used or investigated for preventing migraines.

Beta-blockers are usually prescribed to reduce high blood pressure. Some beta-blockers, however, are also useful in reducing the frequency of migraine attacks and their severity when they occur. Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. Metoprolol (Toprol), atenolol (Tenormin), and nadolol (Corgard) are also being studied for migraine prevention.

Side Effects. Side effects may include:

Fatigue and lethargy are common.
Some people experience vivid dreams and nightmares, depression, and memory loss.
Dizziness and lightheadedness may occur upon standing.
Exercise capacity may be reduced.
Other side effects may include cold extremities, asthma, decreased heart function, gastrointestinal problems, and sexual dysfunction.

If side effects occur, the patient should call a doctor, but it is extremely important not to stop the drug abruptly. Some evidence suggests that people with migraines who have had a stroke should avoid beta-blockers.

Anti-seizure drugs, also called anti-epileptic drugs or anticonvulsants, affect the neurotransmitter gamma aminobutyric acid (GABA), which helps prevent nerve cells from over-firing. GABA may also have a role in migraines. These drugs are commonly used for epilepsy and bipolar disease. Anti-seizure drugs are more expensive than other drugs. They also have significant side effects. Divalproex sodium (Depakote) and topiramate (Topamax) are the only anti-seizure drugs that are approved for migraine prevention. However, if patients do not respond to either of these drugs, doctors may try other types of anti-seizure medications.

Divalproex Sodium (Depakote). Divalproex sodium (Depakote) was first approved in 1996 for migraine prevention. A once-a-day formulation of divalproex (Depakote ER) was approved in 2000. Doctors sometimes prescribe a similar drug, valproate (Depakene). Pregnant patients should not use these drugs, as they may cause birth defects.

Topiramate (Topamax). In 2004, the Food and Drug Administration approved topiramate for prevention of migraines in adults. Studies from 2006 indicated that the drug works well when used on a long-term basis. Patients in these studies experienced significantly fewer migraines for up to 14 months. Topiramate’s most common side effect is a tingling sensation in the arms and legs. Weight loss is also a side effect. In clinical trials, patients lost an average of 3.8% of their body weight.

Other Anti-Seizure Drugs Under Investigation. Researchers are studying other types of anti-seizure drugs for migraine prevention. These include levetiracetam (Keppra), gabapentin (Neurontin), pregabalin (Lyrica), zonisamide (Zonegran), tiagabine (Gabitril), and the investigational drug lacosamide (LCM).

Side Effects. Anti-seizure medication's side effects vary by drug but may include:

Nausea and vomiting
Diarrhea
Cramps
Hair loss
Dizziness
Sleepiness
Blurred vision
Weight gain
Valproate and divalproex can cause serious side effects of inflammation of the pancreas (pancreatitis) and damage to the liver

Amitriptyline (Elavil, Endep), a tricyclic antidepressant drug, has been used for many years as a first-line treatment for migraine prevention. It may work best for patients who also have depression or insomnia. Tricyclics can have significant side effects, including disturbances in heart rhythms, and can be fatal in overdose. Although other tricyclic antidepressants may have fewer side effects than amitritpyline, they do not appear to be particularly effective for migraine prevention.

Researchers have investigated newer types of antidepressants, including serotonin-reuptake inhibitors(SSRIs), such as fluoxetine (Prozac). However, studies to date do not indicate that SSRIs are helpful for migraine prevention.

Muscle Relaxants. Botulinum toxin A (Botox) injection, a common wrinkle treatment, causes small muscles to relax. This approach is now being used with some success for treating disorders that involve over-excited muscle activity, including myofascial pain syndrome and migraine. One study reported complete migraine relief in more than half of patients being tested and improvement of more than 50% in another 35% of patients. Relief lasted 3 - 4 months with no adverse effects. A study presented at the 2005 meeting of the American Headache Society reported that patients who regularly received Botox injections every 3 months reduced both the frequency of migraine attacks and their reliance on pain medications

Angiotensin Converting Enzyme Inhibitors. Commonly used for treating high blood pressure, angiotensin converting enzyme (ACE) inhibitors block the production of the protein angiotensin, which constricts blood vessels and may be involved in migraine. Studies using the ACE inhibitor lisinopril (Prinivil, Zestril) are reporting significant reduction in migraine attacks.

Angiotensin-Receptor Blockers. Angiotensin-receptor blockers (ARBs) have actions similar to ACE inhibitors, but may have fewer side effects. In one study, patients who took the ARB candesartan (Atacand) had significantly fewer headaches compared to patients who received placebo.

Neurostimulation Devices. Researchers are investigating a transcranial magnetic stimulation (TMS) device to help stop migraines before they occur. The hair dryer-size device is held to the back of the head and delivers quick magnetic pulses. The device is used when a patient experiences the first signs of a migraine. Other types of nerve stimulation devices are also under investigation.

Inhalation Devices. These devices use heat to vaporize a drug so that it can be inhaled into the lungs. Clinical trials are currently testing this device with procholorperazine (Compazine), a tranquilizer drug that is used to treat nausea and vomiting.

Nasal Devices. New types of nasal sprays and powders are being researched. Some of them use capsaicin, the chemical found in cayenne peppers, to help relieve pain.

Skin Patches. The Actyve transdermal patch uses a small battery-powered system to deliver a triptan drug through the skin.

Drugs. New drugs in development include tonabersat (gap junction blocker), trexima (combination triptan and non-steroidal anti-inflammatory drug), and GW274150 (nitric oxide synthase inhibitor).

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.clinicaltrials.gov -- Find clinical trials
www.migraineinfo.org -- National Migraine Association

References

Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, et al. Sumatriptan-naproxen for acute treatment of migraine: a randomized trial. JAMA. 2007 Apr 4;297(13):1443-54.

Lewis DW, Winner P, Hershey AD, Wasiewski WW; Adolescent Migraine Steering Committee. Efficacy of zolmitriptan nasal spray in adolescent migraine. Pediatrics. 2007 Aug;120(2):390-6.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory Group. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007 Jan 30;68(5):343-9.

Monastero R, Camarda C, Pipia C, Camarda R. Prognosis of migraine headaches in adolescents: a 10-year follow-up study. Neurology. 2006 Oct 24;67(:1353-6.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR. Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study. Neurology. 2007 May 15;68(20):1694-700.

Review Date:
11/1/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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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

adam.com

Headaches - cluster

FitSugar — Wed, 08 Oct 2008 17:34:59 -0700

In This Report

Highlights
Introduction
Cluster Headaches
Causes
Prognosis
Risk Factors
Diagnosis
Managing Cluster Headaches...
Treatment for Acute Attacks...
Preventive Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Verapamil May Cause Heart Problems

Verapamil (Calan) is a blood pressure medication that is used "off-label" as a first-line preventive treatment for cluster headaches. However, when used for cluster headache, this drug may sometimes cause dangerous disturbances in heart rhythms (arrhythmia), according to a 2007 study in Neurology. The researchers recommend that patients who take verapamil should receive regular electrocardiograms to monitor for any signs of potential heart problems.

Zolmitriptan for Cluster Headache Treatment

Zolmitriptan (Zomig) nasal spray is a safe and effective treatment for cluster headache pain, indicates a 2007 study in Neurology. Because cluster headache pain can quickly become excruciating, researchers would like to find a treatment that can provide rapid pain relief. In a small study, patients who administered either 5 mg or 10 mg of zolmitriptan during a cluster headache attack received relief within 30 minutes. For some patients, the higher dose took effect within 10 minutes. Zolmitriptan is a triptan drug that is commonly used to treat migraine headaches.

Occipital Nerve Stimulation

Occipital nerve stimulation may be a safer alternative to deep brain (hypothalamus) stimulation. Both investigational neurostimulation techniques involve surgically implanting a wire in the brain. The wire is then attached to a small pacemaker-like device. Neurostimulation is used only for patients with intractable cluster headaches who have not responded to drug therapy. In studies published in 2007 in Lancet and Lancet Neurology, several patients who received occipital nerve stimulation became pain-free or had a reduction in the frequency of their cluster headache attacks.

Introduction

Most people have had headaches. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain is insensitive to pain, so that is not what hurts when you have a headache. Rather, the pain occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary. The category helps to distinguish the many different kinds of headaches and to determine right treatments for each.

A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Migraines are the second most frequently occurring primary headaches. Migraine is referred to as a neurovascular headache because it is most likely caused by an interaction between blood vessel and nerve abnormalities.
Cluster headache is a less common type of primary headache. Although it is sometimes referred to as a neurovascular headache, evidence now suggests that its cause lies in the hypothalamus, a region deep in the brain that regulates, among other functions, the biologic rhythms of the body.

Headaches are usually caused by muscle tension, vascular problems, or both. Migraines are vascular in origin, and may be preceded by visual disturbances, loss of peripheral vision, and fatigue. Most headaches can be relieved by over-the-counter pain medications.

Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

The International Headache Society has developed a classification system that includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily or almost daily and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches, or those lasting fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches, which last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

Click the icon to see an image of the different types of headache.

Cluster Headaches

Cluster headaches are among the most painful, and least common, of all headaches. The pain can be so excruciating that they are sometimes referred to as “suicide headaches." Their signature is a pattern of periodic cycles (“clusters”) of headache attacks, which may be either:

Episodic. Attacks occur regularly for 1 week to 1 year, separated by long pain-free periods that last at least 1 month. Between 80 – 90% of patients have episodic cycles. A significant percentage of people who experience a first cluster attack do not have another one.
Chronic. Attacks occur regularly for more than 1 year, with pain-free periods lasting less than 1 month. Between 10 – 20% of patients have chronic cluster headaches. The chronic form is very difficult to treat.

Cluster headaches usually strike suddenly and without warning, although some people experience a migraine-type aura before the attack. A stabbing pain quickly develops behind one eye or on the temple of one side of the head. The pain then spreads to the forehead, jaw, upper teeth, or neck. The pain and other symptoms usually remain on one side of the head.

Other typical symptoms include:

Swollen or droopy eyelid
Watery, tearing eye
Contraction of the eye pupil
Stuffy or runny nose
Forehead and facial sweating
Restlessness and agitation
Nausea and vomiting
Intolerance to light and sound

The symptoms of a cluster headache include stabbing severe pain behind or above one eye or in the temple. Tearing of the eye, congestion in the associated nostril, and pupil changes and eyelid drooping may also occur.

Typical Cluster Cycles

Timing of an Attack. Headache attacks tend to occur with great regularity at the same time of day. (For this reason, cluster headaches are sometimes referred to as “alarm clock” headaches.) About 75% of attacks occur between 9 p.m. - 10 a.m. Attacks may also peak between 1 - 3 p.m.

Duration of an Attack. A single cluster attack is usually brief but extremely painful, lasting about 15 minutes – 1.5 hours if left untreated.

Number of Attacks per Day. During an active cycle, people can experience as few as 1 attack every other day to as many as 8 attacks a day.

Duration of a Cycle. Attack cycles typically occur seasonally -- most often in spring and autumn. Usually a patient has one or two cycles per year that each last 1 - 3 months.

Headache-Free Remissions Between Cycles. Such cycles are followed by headache-free periods lasting at least several weeks, and often for many months. Sustained remissions can last for 20 years.

Migraine Headache: General Description of Its Course

Migraine is now recognized as a chronic illness, not simply as a headache. Migraines are often classified by whether they are accompanied by auras:

Common migraines are without auras; about 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times. In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Such prodrome symptoms can include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in 20 - 25% of patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).

Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from 4 - 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity
Nausea, sometimes with vomiting
Visual symptoms
Facial tingling or numbness
Extreme sensitivity to light and noise
Looking pale and feeling cold

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

Tension-Type Headache

Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and may have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.

People who suffer from tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Other Primary Headaches

Chronic Paroxysmal Hemicrania. Chronic paroxysmal hemicrania is a close relative of cluster headache and very similar. It causes multiple, short, and severe daily headaches with similar symptoms. Unlike cluster headaches, the attacks are shorter (1 - 2 minutes) and more frequent (occurring an average of 15 times a day). This headache is even rarer than cluster headache, tends to occur in women, and always responds to treatment with indomethacin.

Hemicrania Continua. Hemicrania continua occurs mostly in women. The patient generally experiences continuous low-level headache always on one side of the face. Periodic attacks can last days to weeks, which can be mild to severe, and may resemble migraines. (About 10% of patients experience remissions.) The headaches can usually be treated successfully with indomethacin, which helps differentiate if from other headaches, notably migraines.

SUNCT Syndrome. A disorder called SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) causes stabbing or burning eye pain that may resemble cluster headaches, but attacks are very brief (lasting about a minute) and may occur more than 100 times per day. Red and watery eyes, sweating forehead, and congestion are typical. This rare headache is more common in men and does not respond to other headache treatments.

Causes

Cluster headaches, like migraines, are likely due to an interaction of abnormalities in the blood vessels and nerves that affect regions in the face.

Evidence strongly suggests that abnormalities in the hypothalamus, a complex structure located deep in the brain, may play a major role in cluster headaches. Advanced imaging techniques have shown that a specific area in the hypothalamus is asymmetrical in these patients and is activated during a cluster headache attack.

The hypothalamus is involved in the regulation of many important chemicals and nerve pathways, including:

Click the icon to see an image of the hypothalamus.

Nerve clusters that regulate the body's biologic rhythms (its circadian rhythms)
Serotonin and norepinephrine. These are neurotransmitters (chemical messengers in the brain) that are involved with well-and appetite.
Cortisol (stress hormones)
Melatonin (a hormone related to the body's response to light and dark)
Beta-endorphins (substances that modulate pain)

Circadian Abnormalities. Cluster attacks often occur during specific sleep stages. They also often follow the seasonal increase in warmth and light, beginning in summer and ending in the fall. Researchers have therefore focused attention on circadian rhythms, and in particular small clusters of nerves in the hypothalamus that act like biologic clocks.

The most important nervous cluster is the suprachiasmatic nuclei (SCN), which appears to help coordinate the body's activities (sleep/wake) with the environment (dark/light). Some studies support the idea that some failure in this biologic pacemaker may impair the pain control system and cause these terrible attacks.

The hormone melatonin is also involved in the body's biologic rhythms.

Alterations in Serotonin. The brain chemical serotonin is of particular interest in the study of headaches, particularly migraine and cluster headaches. This neurotransmitter (chemical messenger) affects, among other functions, well-being, sleep, and appetite. Some research has also suggested that serotonin may play an important role in the way circadian rhythms are expressed. There is some evidence of abnormal regulation of brain serotonin levels in patients with cluster headaches (although it is not as pronounced as in patients with migraine).

Cluster headaches are associated with dilation (widening) of blood vessels and inflammation of nerves behind the eye.

Cluster headaches may be caused by blood vessel dilation in the eye area. Inflammation of nearby nerves may give rise to the distinctive stabbing, throbbing pain usually felt in one eye. The trigeminal nerves branch off the brainstem behind the eyes and send impulses throughout the cranium and face.

In both cluster and migraine headaches blood vessels dilate, but in cluster headaches only the blood vessels behind the eyes pulsate. What causes these events and how they relate to cluster headaches are still unclear:

Because blood vessel dilation appears to follow, not precede, the pain, some action originating in the brain is likely to be part of the primary process.
Some experts believe that at least some of the pain is caused by dilation in branches of the carotid artery (a major artery that supplies the brain with blood).
Certain substances, such as histamine and a protein called endothelin-1 that widens blood vessels and are being investigated for a possible role in cluster headaches.

Nitric Oxide. Nitric oxide is a small molecular messenger that activates nerve pathways in the brain, muscles, or elsewhere. It may contribute to major primary headaches (tension-type, cluster, and migraines) by specifically triggering inflammation and overactivity in the trigeminal nerves. (This is a major nerve pathway that runs from the brain stem to the head and face.) However, other factors must be present that make patients with cluster headaches susceptible to the actions of nitric oxide.

Immune Abnormalities. Researchers are also investigating whether overproduction of certain immune factors called cytokines may contribute to cluster headaches. Cytokines, such as interleukins, are known to cause inflammation and injury in high amounts. To date, however, there is no evidence that they play any role.

Abnormalities in the Sympathetic Nervous System. Some evidence suggests that abnormalities in the sympathetic (also called autonomic) nervous system may contribute to cluster headaches. This system regulates non-voluntary muscle actions in the body, such as in the heart and blood vessels.

About 90% of people seeking help for headaches have a primary headache. The rest have secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. Both types of headache even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side. Even if pain affects both sides of the head, it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also called TMD), which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Click the icon to see a depiction of glaucoma.

Click the icon to see an image of the slitlamp test.

Click the icon to see an image of the visual field test.

Brain Tumor. Fear of brain tumor is common among people with headaches, but headache is almost never the first or only sign of a tumor. Changes in personality and mental functioning, vomiting, seizures, and other symptoms are more likely to appear first. When the headache does develop, it is often worse early in the morning or may awaken sufferers during the night.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, the weight of evidence suggests that hypertension does not cause head aches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Head Injuries. It is obvious that a significant blow to the head will cause pain. In most cases, the pain is similar to tension-type headache and is treated in the same way as the primary headache. Post-injury headaches, however, can reflect serious damage, ranging from skull fractures to internal bleeding, and monitoring is important.

Disorders of the Meninges. The meninges are the membranes covering the brain and the spinal cord. Meningitis, which is an infection or irritation of these membranes, is an uncommon but potentially serious cause of severe headache. Other symptoms include nausea and stiffness or pain in the neck.

Miscellaneous Causes of Benign Headaches. Rapid consumption of ice cream or other very cold foods or beverages is the most common trigger of sudden headache pain, which may be prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Other common benign causes of headache include eyestrain, dental problems, allergies, systemic infections, and caffeine withdrawal. Headaches may be induced by sexual activity or intense physical exertion. Leakage from spinal cord fluid is rare but can cause headaches that may be mistaken for brain tumors.

Prognosis

The pain of cluster headaches can be intolerable. In fact, a higher-than-average rate of suicide has been reported in men with these headaches. Eventually, the attacks cease, but experts cannot predict when or how they will end.

People with episodic cluster headaches tend to have low sexual appetites and impaired verbal memory and are more likely to suffer from anxiety. According to one study, nearly a quarter of patients with cluster headaches met the criteria for having anxiety disorders. Furthermore, the anxiety disorders occurred more frequently within the year before the onset of their cluster headaches. (None of these patients had depression or abused alcohol or drugs.) Some studies suggest that the biologic abnormalities in the hypothalamus of the brain that are associated with episodic cluster headaches may also contribute to these emotional and mental difficulties.

In rare cases, patients with cluster headaches have migraine-like aura. Headaches that are accompanied by aura may increase the risk of stroke or transient ischemic attack (TIA). A 2005 study found that patients who had headaches with auras were about four times more likely to have a stroke or TIA than patients who had headaches without aura. TIA symptoms are similar to those of stroke, but last only briefly. A TIA is often a warning sign that a person is at risk for a more severe stroke.

Headaches with auras may also increase the risk for eye retinal damage (retinopathy), which can lead to severe vision problems or blindness. The risks for stroke and retinopathy are associated with the effects of aura-related headaches on small blood vessels in the brain and the eyes.

Risk Factors

Cluster headaches are rare, affecting less than 1% of the population.

Cluster Headaches in Men. Cluster headaches are much more common in men than in women, about 85% of cluster headache sufferers are men. The peak age of onset for men is the 20s to early 30s.

Cluster Headaches in Women. Studies of cluster headaches in women report that there are two ages of peak onset, the 20s and 50s. In some studies, attacks in women were of shorter duration than in men, but the duration of the episodes and length of remission were similar. Unlike with migraines, fluctuations in estrogen and other female hormones do not appear to influence the onset of attacks, although attacks may be less frequent during pregnancy.

Cluster headaches typically start in the late twenties. In rare cases they begin in childhood, and about 10% of cases develop after age 60.

Lifestyle factors, including smoking, alcohol abuse, and stress (in particular stressful work situations), appear to play a very strong role in cluster headaches. Smoking or alcohol use can trigger attacks. In a 2006 study, 70% of people with cluster headaches were current smokers. About half reported that alcohol (most commonly red wine) triggered an attack.

Evidence for genetic factors has been weak, but there is a growing body of research suggesting a family history in about 5 - 10% of patients. Some evidence suggests that cluster headaches in women may be more likely to be genetically based, particularly when they first occur at younger ages.

One study reported that 26% of cluster headache sufferers also had a personal history of migraines, and 33% had a family history of this headache. Studies have reported that about 15% of patients have both kinds.

Head injury may also increase the risk of cluster headaches. In one study, over 13% of patients reported a history of a head injury that caused loss of consciousness, and nearly a quarter had experienced a head injury without loss of consciousness.

Cluster headaches tend to occur during specific sleep stages and have been associated with several sleep disorders, including narcolepsy, insomnia, and sleep apnea.

Sleep apnea, a disorder in which a person stops breathing during the night, perhaps hundreds of times, is of particular interest. Studies have reported sleep apnea in 30 - 80% of patients with cluster headaches. One study suggested that in some people apneas may trigger cluster headache during the first few hours of sleep, making patients susceptible to follow-up attacks during the following midday to afternoon periods. Treating patients who have both disorders with a device called CPAP, which opens the airways, may help improve both conditions. [See In-Depth Report #65: Sleep apnea.]

The following conditions and substances might trigger cluster attacks:

Alcohol
High altitudes (trekking, air travel)
Bright light (including sunlight)
Exertion
Heat (hot weather, hot baths)
Foods high in nitrites (such as bacon and preserved meats)
Certain medications (including those that cause blood vessel dilation, such as nitroglycerin, and various blood pressure medications)
Cocaine

Triggers usually have an effect only during active cluster cycles. When the disorder is in remission, such triggers rarely set off the headaches.

Diagnosis

In two surveys, patients reported a delay of 1 - 6 years in the diagnosis of their headaches. In one of the surveys, migraine-like symptoms (light and sound sensitivity and nausea) were major reasons for the frequent misdiagnosis by family doctors. About a third of the patients sought help from dentists and another third from ear-nose-throat specialists. In most cases, patients were inappropriately treated for other types of headaches (including having sinus surgery).

For an accurate diagnosis, the patient should describe:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Pain intensity
Associated symptoms (visual disturbances or nausea and vomiting)
Behaviors during a headache
Snoring, sleep disturbances, and daytime sleepiness (which could relate to sleep apnea, a possible risk factor for cluster headaches)

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches:

Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.
Tracking medications is an important way of identifying so-called rebound headaches, which can arise when drugs that are taken frequently are discontinued.
Be sure to attempt to define the intensity of the headache. It may be indicated by using a number system:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work or activities

3 = Distracts from work or activities

4 = Makes work or activities very difficult

5 = Incapacitating

To diagnose a chronic headache, the doctor will examine the head and neck and usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

As part of the diagnosis, a doctor should rule out other headaches and disorders. If the results of the history and physical examination suggest other or accompanying causes of headaches or serious complications, extensive imaging tests are performed.

Migraines. Cluster headaches are often misdiagnosed as migraines but they are quite different:

Frequency and Duration. Cluster headaches generally last 15 minutes to a few hours and can occur several times a day. A single migraine attack is continuous over the course of one or several days.
Behavior. Cluster headache sufferers tend to move about while migraine sufferers usually want to lie down.

Nevertheless, in both cases, the headache suffers can be highly sensitive to light and noise, which may make it difficult to distinguish between them.

Other Headaches. Other headaches that resemble migraines include SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and chronic paroxysmal hemicrania, which are other primary headaches, and some secondary headaches notably trigeminal neuralgia (TN), temporal arteritis, and sinus headaches. Cluster symptoms, however, are usually precise enough to rule out these other types of headaches.

Tear in the Carotid Artery. A tear in the carotid artery (which leads to the brain) can cause pain that resembles a cluster headache. People with this condition may even respond to sumatriptan, a drug used to treat a cluster attack. Doctors should consider imaging tests for patients with a first episode of cluster headache in which this event is suspected.

Orbital Myositis. An unusual condition called orbital myositis, which produces swelling of the muscles around the eye, may mimic symptoms of cluster headache. This condition should be considered in patients who have unusual symptoms such as protrusion of the eyeball, painful eye movements, or pain that does not dissipate within three hours.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems
If headaches wake patients during the night
If new headaches develop in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls)
If headaches are becoming worse

Imaging tests are not recommended for patients with migraines and no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may help rule out brain disorders or headaches caused by chronic sinusitis.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Managing Cluster Headaches

Patients with cluster headaches face significant difficulties in the management and treatment of their problems:

In two surveys, patients reported a delay in the diagnosis of their headaches of 1 - 6 years. In most of these cases, patients were inappropriately treated for other headaches (including having sinus surgery).
Treatment for cluster headaches is problematic because most attacks come on suddenly and occur daily, while episodic cycles may continue for weeks or months. Most oral medications used for other headaches act too slowly to have much effect on a cluster headache, which typically lasts about an hour. Injected or intravenous headache medications may work but they cannot be used on a daily basis. The emphasis in managing cluster attacks, therefore, is in preventing them. Verapamil and corticosteroid drugs are most commonly used for prevention.
Cluster headaches are difficult to study. First, they are very uncommon, so there are few well-controlled investigations of this problem. Second, the placebo response is very high in studies on cluster headaches, with 7 - 43% of patients responding to dummy treatments.

The most effective treatments for a cluster attack are:

Oxygen inhalation
Triptan drugs (injections of sumatriptan)

Relief can occur in 5 - 10 minutes.

Because effective therapy for cluster headaches is limited, most research efforts focus on the prevention of attacks during cluster cycles. A number of treatments are available and may be used alone or in combination. In general, the steps for preventive management are:

Transitional Medications. Patients should use headache medications (typically a triptan, a corticosteroid, or ergotamine) to control any attacks during the transition to on-going maintenance drugs.

Maintenance Drugs. Prevention of attacks during a cluster cycle is extremely important. Although patients with episodic or chronic cluster headaches may take different medications, there does not appear to be much difference in their effectiveness for either type. The following are the most commonly used preventive drugs:

Calcium-channel blockers. The calcium-channel blocker verapamil is most often used for preventing cluster headaches.
Corticosteroids. Tapered doses of corticosteroids, such as prednisone, may be useful for preventing episodic cluster headaches.
Lithium. Some studies suggest that lithium is the best drug for chronic cluster headaches.
Methysergide. This drug is a serotonin inhibitor and is sometimes used for episodic cluster headaches.
Antiseizure drugs. Of the antiseizure drugs, valproic acid is most often used. Others that may be useful include carbamazepine, gabapentin, and topiramate.
Ergotamine. Some doctors start with ergotamine, which is useful as a transitional medication.

Doctors have prescribed other drugs, including indomethacin, melatonin, beta blockers, tricyclic and other antidepressants, and capsaicin. Some patients may need a combination of medicines.

Lifestyle Changes. Patients should avoid the following:

Alcohol.
Foods containing nitrates or nitrites (such as smoked meats). No other dietary factors appear to play a role, for good or ill, in this disease.
Medications containing nitrates (such as nitroglycerin).
Smokers who can't quit should at least stop at the first sign of an attack and not smoke throughout a cycle.

One study suggested that vigorous physical exertion at the sign of an attack onset may help reduce or even abort an attack.

Treatment for Acute Attacks

Breathing pure oxygen (by face mask, for 15 minutes or less) is one of the most effective and safest treatments for cluster headache attacks. It is often the first choice. Inhalation of oxygen raises blood oxygen levels, therefore relaxing narrowed blood vessels.

Triptans are drugs that are usually used to treat migraine headaches. They can also help stop a cluster attack. Injections of sumatriptan (Imitrex) are the standard triptan treatment. Sumatriptan injections work within 15 minutes in about three quarters of cluster attacks. The nasal spray form is also effective, and generally provides relief within 30 minutes. The spray seems to work best for attacks that last at least 45 minutes, although some people find it does not work as well as the injectable form.

Newer triptans used for cluster headache treatment include rizatriptan (Maxalt), naratriptan (Naramig, Amerge), and zolmitriptan (Zomig). Several 2006 and 2007 studies of zolmitriptan nasal spray indicated it was effective for cluster headache relief with few side effects.

Side Effects. Many of the newer triptans may have fewer severe side effects than sumatriptan. Side effects of most triptans, however, may include:

Nausea
Dizziness
Muscle weakness
Heaviness or pressure in the chest
Tingling and numbness in the toes
Rapid heart rate

Complications of Triptans. The following are potentially serious problems with triptans.

Complications on the Heart and Circulation. Triptans narrow (constrict) blood vessels. Because of this action, spasms in the blood vessels may occur, which can cause stroke and heart attack. This is a rare but very serious side effect. Patients with a history of heart attack, stroke, angina, uncontrolled high blood pressure, peripheral artery disease, or heart disease should not use triptan drugs.
Serotonin Syndrome. Serotonin syndrome is a life-threatening condition that occurs from an excess of the brain chemical serotonin. Triptans, as well as certain types of antidepressant medications, can increase serotonin levels. These antidepressant drugs include serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) and venlafaxine (Effexor). It is very important that patients not combine a triptan drug with an SSRI or SNRI drug. Serotonin syndrome is most likely to occur when starting or increasing the dose of a triptan or antidepressant drug. Symptoms include restlessness, hallucinations, rapid heartbeat, tremors, increased body temperature, diarrhea, nausea, and vomiting. You should seek immediate medical care if you have these symptoms.

The following groups should avoid triptans or take them with caution and only under doctor supervision:

Anyone with a history or any risk factors for stroke, uncontrolled diabetes, high blood pressure, or heart disease.
People taking antidepressants that increase serotonin levels.
Pregnant women. Studies on the effects of triptans in this group are limited. One study suggested a higher incidence of preterm deliveries in pregnant women taking sumatriptan. No higher rates of still births or birth defects were reported. In general, pregnant women should avoid any medications if possible.

Injections of the ergotamine-derived drug known as dihydroergotamine (DHE) can stop cluster attacks within 5 minutes in many patients, offering benefits similar to injectable sumatriptan. Ergotamine is also available in the form of a nasal spray, rectal suppositories, and tablets. Ergotamine can have dangerous drug interactions with many medications. All ergotamine products approved by the Food and Drug Administration (FDA) contain a "black box" warning in the prescription label explaining these drug interactions. In 2007, the FDA pulled 15 unapproved older ergotamine products off the market, in part because they lacked this warning label.

Methysergide (Sansert) is another ergot-based drug that is used for preventing episodic cluster headaches. (It is not very effective for chronic cluster headaches.) Improvement usually occurs within a few days, although it may be delayed for up to 2 weeks. Prolonged methysergide therapy can cause serious side effects, including scarring of internal organs, so it cannot be used long term. This is not usually a problem for patients with cluster headaches, since they need the drug only for about 4 - 6 weeks. Nevertheless, patients should immediately report to their doctors any of the following symptoms: cold, numb, and painful hands and feet; leg cramps on walking; any type of back or chest pain.

Lidocaine, a local anesthetic, may be useful in nasal-spray or nasal-drop form for stopping cluster attacks. Some reports suggest that it is helpful for most patients within about 40 minutes.

Preventive Medications

Calcium-channel blockers, commonly used to treat heart disease, are important drugs for preventing cluster headaches. Verapamil (Calan) is the standard calcium-channel blocker used for headache prevention. Constipation is a common side effect. Verapamil can also cause irregular heartbeats (arrhythmia), according to a 2007 study in Neurology. Patients who take verapamil for cluster headaches should have frequent electrocardiograms (EKGs) to monitor any potential development of arrhythmia.

People taking calcium-channel blockers should not stop taking the drug abruptly. Doing so can dangerously increase blood pressure. Overdose can cause dangerously low blood pressure and slow heart beats. Drinking grapefruit juice or eating grapefruit with these drugs can enhance their potency, sometimes to toxic levels that can cause heart failure in patients with heart disease.

Lithium (Eskalith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, can also help prevent cluster headaches. The patient usually receives benefit within 2 weeks of starting to take the drug, and often within the first week. Lithium may be used alone or with other drugs.

Side Effects. Side effects include:

Trembling hands
Nausea
Increased urine output
Some loss of coordination

More severe reactions, which occur at higher blood levels, are:

Convulsions
Uncontrolled jerky movements in arms and legs
Blurred vision
Vomiting
Stupor
Coma

Very high blood levels of lithium can be fatal.

Long-Term Side Effects. Even for patients who do not have a toxic response, long-term use of lithium is not without problems. Some patients may experience:

An unpleasant taste in the mouth
Hair loss
Weight gain (a frequent reason why many patients stop taking lithium)
Skin eruptions that can resemble acne (lithium can also worsen psoriasis in patients who have this condition)
Thyroid problems -- Up to 20% of patients who take lithium develop symptomatic hypothyroidism (low thyroid), and another 20 - 30% develop hypothyroidism without symptoms
Increased risk for diabetes
Blunted sexual drive
Dulled emotions and mental acuity
Memory loss
Lack of motor coordination
Reduced sensitivity to light -- This may slightly affect color recognition and cause problems with night driving; patients wear sunglasses outside and avoid extensive exposure to bright light

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include:

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Thiazide diuretics
ACE inhibitors

There have been reports of interactions between lithium and certain drugs commonly used in combination, including:

Antipsychotics
Anticonvulsants
Calcium-channel blockers

Other Factors That Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels, including:

Seasonal change
Menstrual cycle (lithium levels may drop during the premenstrual phase)
Weight loss
Changes in salt intake
Dehydration
Diarrhea

Patients should contact their doctor if they have any suspicious symptoms or illnesses.

Valproate. The anti-epileptic drug valproate (valproic acid, divalproex sodium, Depakene, Depakote) has been used with some success for preventing cluster headaches. It controls pain and reduces the frequency of attacks by more than half in many people with episodic or chronic cluster headaches. Side effects include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). It can also cause birth defects and, in rare cases, liver toxicity.

Topiramate. Other, newer anti-seizure drugs that have fewer side effects are being investigated for chronic headaches. Studies on topiramate (Topamax) are promising. In small trials of topiramate, up to 87% of patients achieved remission, and 60% achieved a complete response. Still, about 25% of patients stop using it, either because it doesn't work or because the side effects are intolerable. They can include drowsiness, mood changes, tremor, and confusion.

Gabapentin. Another anti-seizure drug that has shown some benefit in isolated cases is gabapentin (Neurontin). Research on this drug in patients with cluster headaches, however, remains very limited.

Side Effects of Valproate and Other Anti-Seizure Drugs. The side effects given here are mostly associated with valproate. Other anti-seizure drugs have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy, and then subsiding. Those of valproate include:

Gastrointestinal problems (nausea, vomiting, heartburn)
Visual disturbances
Ringing in the ear
Hair loss
Weight changes (weight gain is a significant problem with valproate, while weight loss occurs with topiramate)
Agitation
Odd movements
In women, menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)

Very serious side effects are rare but include the following:

Liver damage
Convulsions
Coma
Pancreatitis (inflammation of pancreas) in adults and children
Significant increase in risk for birth defects in pregnant women

A nasal spray form of capsaicin called civamide (Zucapsaicin) has shown promise in the prevention and treatment of cluster headaches. Capsaicin is a component of hot red peppers that seems to reduce substance P, a chemical in the body that contributes to inflammation and the delivery of pain impulses. In a small study, daily use of intranasal civamide resulted in more than a 50% reduction in headaches. Side effects include a burning sensation and excessive tearing.

Transitional medications are used after cluster episodes to stabilize the patient until preventive maintenance becomes effective.

Corticosteroid drugs (also called steroids) are very useful as transitional drugs for stabilizing patients after an attack until a maintenance drug, such as a calcium-channel blocker, begins to take effect. Prednisone (Deltasone) and dexamethasone (Decadron) are the standard steroid drugs used for short-term cluster headache transitional treatment. These drugs are typically taken for a week and then gradually tapered off. If headaches return, the patient may start taking the steroid again. Unfortunately, long-term use of steroids can lead to serious side effects so they cannot be taken for on-going prevention.

Angiotensin Receptor Blockers. Angiotensin receptor blockers (ARBs) are used to treat high blood pressure. Candestan (Atacand) is being investigated as a potential preventive medication for cluster headache.

Botulinum. Botulinum toxin A (Botox) injections are being used for several conditions requiring muscle relaxation, including smoothing wrinkles. (This potentially deadly toxin is very safe when minuscule amounts are injected into small muscles.) Botox has shown promise for migraine and tension headache sufferers and is now being studied for cluster headaches as well.

Melatonin. Small reports indicate that melatonin, a brain hormone that helps to regulate the sleep-wake cycle, may help prevent episodic or chronic cluster headaches. Melatonin supplements are sold in health food stories, but as with most natural remedies, the quality of different preparations varies, and they have not been rigorously tested for safety or effectiveness. Hormones such as melatonin are powerful substances, and additional studies are needed.

Glucosamine. There have been some reports that glucosamine, an alternative remedy commonly used for osteoarthritis, may prevent migraine attacks. Some researchers theorize this substance may reduce inflammation that affects nerves involved in vascular headaches. Whether it has any effect on cluster headaches is unknown.

Additional Therapies. Many patients with cluster headaches try alternative remedies for relief of pain. Treatments may include acupuncture, herbs, chiropractic, homeopathic remedies, reflexology, hypnosis, spiritual therapies, massage, aromatherapy, relaxation techniques, and yoga.

Surgery

Surgical intervention may be considered for patients with chronic cluster headaches that do not respond to treatments. Patients whose headaches have not gone into remission for at least a year may also be candidates for surgery. Most surgical approaches for cluster headache are still considered experimental. Surgy has shown limited success and can have distressing side effects. However, some surgical techniques, such as deep brain electrical stimulation, are showing promise.

Deep brain stimulation (also called neurostimulation) may relieve chronic cluster headaches in some patients who do not respond to drug therapy. A similar technique is approved for treating the tremors associated with Parkinson’s disease. The surgeon implants a tiny wire in a specific part of the hypothalamus. The wire, meanwhile, receives electrical pulses from a small generator implanted under the collarbone.

Although only a handful of patients have been treated, results to date are promising. Some patients have remained completely free of pain for an average of more than 7 months when the electrode is switched on. When the device is turned off, headaches reappear within days to weeks. The procedure is reversible and appears to be generally safe, although a few cases of fatal cerebral hemorrhage have occurred.

Occipital nerve stimulation is being investigated as a less invasive alternative to hypothalamus stimulation. Two 2007 studies in Lancet and Lancet Neurology reported promising results in a small group of patients with cluster headaches. Some patients became pain-free, while others had reduced frequency of headache attacks. Researchers suggest that occipital nerve stimulation may be less risky than deep brain stimulation.

The vagus nerve runs between the brain and the abdomen. Vagus nerve stimulation (VNS) is a surgical procedure in which a small generator is placed under the skin on the left side of the chest. A surgeon makes a second incision in the neck and connects a wire from the generator to the vagus nerve. A doctor programs the generator to send mild electrical pulses at regular intervals. These pulses stimulate the vagus nerve.

VNS is sometimes used to treat epilepsy and depression that does not respond to drugs. It is also being investigated as a possible treatment for chronic migraine and cluster headaches. In a 2005 study of six patients, VNS improved headache and helped a few patients return to work.

Percutaneous Radiofrequency Retrogasserian Rhizotomy. Percutaneous radiofrequency retrogasserian rhizotomy (PRFR) generates heat to destroy pain-carrying nerve fibers in the face. Small studies have reported good to excellence results in 83 - 92% patients. Unfortunately complications are common and include numbness, weakness during chewing, changes in tearing and salivation, and facial pain. In severe, but rare, cases, complications include damage to the cornea and vision loss.

Percutaneous Retrogasserian Glycerol Rhizolysis. Percutaneous retrogasserian glycerol rhizolysis (PRGR) is a less invasive technique than PRFR and has fewer complications. It involves injections of glycerol to block the facial nerves that cause the pain. In one study, 83% of patients reported immediate relief after one or two injections. Cluster headaches recurred, however, in about 40% of the patients.

Microvascular Decompression of the Trigeminal Nerve. Microvascular decompression frees the trigeminal nerve from any blood vessels that are pressing against it. In one study, over 73% of patients reported at least 50% relief. Half of these patients reported 90% relief, but the level of benefit fell to less than 50% over time. Repeat procedures are rarely successful. The procedure is risky, and possible complications include nerve and blood vessel injury and spinal fluid leakage. It does not, however, have the common nerve damage effects in the face that PRFR does.

Resources

www.i-h-s.org -- International Headache Society
www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.ouch-us.org -- Organization for Understanding Cluster Headaches
www.clusterheadaches.com -- Support group for people with cluster headaches

References

Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow-up of eight patients. Lancet. 2007 Mar 31;369(9567):1099-106.

Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol. November 2006. [Epub ahead of print 11 September 2006]

Cohen AS, Matharu MS, Goadsby PJ. Electrocardiographic abnormalities in patients with cluster headache on verapamil therapy. Neurology. 2007 Aug 14;69(7):668-75.

Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet Neurol. 2007 Apr;6(4):314-21.

Rapoport AM, Mathew NT, Silberstein SD, Dodick D, Tepper SJ, Sheftell FD, Bigal ME. Zolmitriptan nasal spray in the acute treatment of cluster headache: a double-blind study. Neurology. 2007 Aug 28;69(9):821-6.

Schurks M, Kurth T, de Jesus J, Jonjic M, Rosskopf D, Diener HC. Cluster headache: clinical presentation, lifestyle features, and medical treatment. Headache. 2006 Sep;46(:1246-54.

Sostak P, Krause P, Forderreuther S, Reinisch V, Straube A. Botulinum toxin type-A therapy in cluster headache: an open study. J Headache Pain. 2007 Sep 24; [Epub ahead of print]

Van Vliet JA, Eekers PJ, Haan J, Ferrari MD; Dutch RUSSH Study Group. Evaluating the IHS criteria for cluster headache -- a comparison between patients meeting all criteria and patients failing one criterion. Cephalalgia. 2006 Mar;26(3):241-5.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Headaches - tension

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Prognosis
Causes
Risk Factors
Diagnosis
Managing Tension-Type Heada...
Medications
Treatment
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Global Prevalence of Tension-Type Headache

Tension-type headaches account for nearly half of all headaches, according to a 2007 study in Cephalagia. The researchers estimated that more people are disabled by tension-type headache than by migraine.

Causes of Tension-Type Headaches

Doctors are not really sure why tension-type headaches occur. Possible causes include muscle contractions or changes in brain chemicals. Several studies in 2006 and 2007 presented the theory that tension-type headaches may be due to myofascial trigger points in the shoulders and neck, as well as poor head posture. Some researchers suggest that tension-type headaches may be related to fibromyalgia, a condition that is also characterized by myofascial pain.

Tension-type headaches may be triggered by:

Chronic poor posture
Overwork and stress
Lack of sleep
Dental problems, including temporomandibular joint disorder (TMJ)
Certain types of foods
Skipping meals
Medication overuse
Hormonal changes related to menstruation

Managing Tension-Type Headaches

Acetaminophen (Tylenol) or non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), or ketoprofen (Actron, Orudis KT) can usually provide pain relief for tension-type headache attacks. Patients who have chronic headaches sometimes take amitriptyline (Elavil), a prescription tricyclic antidepressant, to help prevent attacks. Exercise, stress reduction, and relaxation techniques are very important lifestyle approaches for controlling tension-type headaches.

Introduction

Most people are familiar with headaches, the all too common affliction marked by throbbing, piercing, or vise-like pain around much or a part of the head. There are many different kinds of headaches, and they range from being an infrequent annoyance to a persistent, severe, and disabling medical condition.

The brain itself is insensitive to pain, so that is not what hurts when a headache arises. The pain, instead, occurs in the following locations:

The tissues covering the brain
The attaching structures at the base of the brain
Muscles and blood vessels around the scalp, face, and neck

Doctors categorize headaches as either primary or secondary, which helps to distinguish the many different kinds of headaches and to determine appropriate treatments for each.

Primary Headaches. A headache is considered primary when a disease or other medical condition does not cause it. Most primary headaches fall into three main types: Tension-type, migraine, and cluster headaches.

Tension headache is the most common primary headache and accounts for 90% of all headaches.
Neurovascular headaches are the second most frequently occurring primary headaches and include migraines (the more common) and cluster headaches. Such headaches are caused by an interaction between blood vessel and nerve abnormalities. [See In-Depth Report #97: Migraine headaches and In-DepthReport #99: Cluster headaches.]

Symptoms of migraine and tension-type headaches often overlap, and a diagnosis is sometimes difficult.

Secondary Headaches. Secondary headaches are caused by other medical conditions, such as sinus infections, neck injuries, and strokes. About 2% of headaches are secondary to abnormalities or infections in the nasal or sinus passages, and they are commonly referred to as sinus headaches.

Chronic Daily Headaches. The International Headache Society's classification system includes a category called chronic daily headaches. They may originate as tension headaches, migraines, or a combination of these or other headache types. Chronic daily headaches affect 4 - 5% of the population.

Click the icon to see an image of the different types of headache.

Chronic daily headaches are defined as any benign headache that occurs at least 15 days a month and is not associated with a serious neurologic abnormality. Most people with these headaches have them daily, or almost daily, and they can be quite debilitating.

Chronic daily headaches are, in turn, subdivided into two categories:

Short-duration headaches last fewer than 4 hours. The most common short-acting chronic headaches are cluster headaches.
Long-duration headaches last more than 4 hours. Tension-type headaches are the most common type of long-duration chronic (recurring) headaches and, in fact, the most common type of chronic headaches in general.

General Description. Tension-type headaches, also called muscle contraction headaches or simply tension headaches, are the most common of all headaches. Tension-type headaches can last minutes to days and have the following characteristics:

The pain is commonly described as a tight feeling, as if the head were in a vise. It usually occurs on both sides of the head and is often experienced in the forehead, in the back of the head and neck, or in both regions. Soreness in the shoulders or neck is common.
Depression, anxiety, and sleeping problems may accompany persistent headaches.
Sufferers of tension-type headaches may also have migraine-like symptoms, including being sensitive to light or noise (but not both). Some patients also may suffer from visual disturbances. (Such symptoms in tension headaches, however, tend to be less severe than in migraine. Tension headaches also do not cause nausea or limit activities to the degree that migraines do.)

Types of Tension Headache. In 2004, the International Headache Society updated its original 1988 classification criteria. Tension-type headaches are now divided into the following four classifications:

Frequent episodic tension-type headache. Headaches occur at least once but not more than 15 days per month for at least 3 months (a minimum of 12 days but not more than 180 days per year). Headaches last from at least 30 minutes to 7 days.
Infrequent episodic tension-type headache. At least 10 episodes of headache that occur less than 1 day per month (12 days per year). Because these headaches occur infrequently, they do not impact a patient's quality of life as severely as frequent episodic headaches and may not require attention from a medical professional.
Chronic tension-type headache. Headaches occur at least 15 days per month for at least 3 months (180 days per year). The headache persists for hours at a time and may be continuous.
Probable tension-type headache. Probable tension headaches may be classified as probable frequent episodic, probable infrequent episodic, or probable chronic. They have most, but not all, of the symptoms of tension-type headaches and are not attributed to migraine without aura or other neurological disorders. Probable chronic tension-type headache may be related to medication overuse.

Migraine Headache: General Description of Its Course. Migraine is now recognized as a chronic illness, not simply as a headache. These headaches are often classified by whether or not auras accompany them:

Common migraines are without auras. About 75% of migraines are the common type.
Classic migraines are those with auras.

A person may experience one or the other at different times.

In general, there are four symptom phases to a migraine (although they may not all occur in every patient): the prodrome phase, auras, the attack, and the postdrome phase.

Prodrome. The prodrome phase is a group of vague symptoms that may precede a migraine attack by several hours, or even a day or two. Prodrome symptoms include:

Sensitivity to light or sound
Changes in appetite
Fatigue and yawning
Malaise
Mood changes
Food cravings

Auras. Auras are sensory disturbances that occur before the migraine attack in between 20 - 25% of patients. Visually, auras are referred to as being positive or negative:

Positive auras include bright or shimmering light or shapes at the edge of their field of vision called scintillating scotoma. They can enlarge and fill the line of vision. Other positive aura experiences are zigzag lines or stars.
Negative auras are dark holes, blind spots, or tunnel vision (inability to see to the side).
Patients may have mixed positive and negative auras. This is a visual experience that is sometimes described as a fortress with sharp angles around a dark center.

Other neurologic symptoms may occur at the same time as the aura, although they are less common. They include:

Speech disturbances
Tingling, numbness, or weakness in an arm or leg
Perceptual disturbances such as space or size distortions
Confusion

Migraine Attack. If untreated, attacks usually last from four to 72 hours. A typical migraine attack produces the following symptoms:

Throbbing pain on one side of the head. The word migraine, in fact, is derived from the Greek word hemikrania, meaning "half of the head" because the pain of migraine often occurs on one side. Pain also sometimes spreads to affect the entire head.
Pain worsened by physical activity.
Nausea, sometimes with vomiting.
Visual symptoms.
Facial tingling or numbness.
Extreme sensitivity to light and noise.
Looking pale and feeling cold.
Less common symptoms include tearing and redness in one eye, swelling of the eyelid, and nasal congestion, including runny nose. (Such symptoms are more common in certain other headaches, notably cluster headaches. In one study, however, they occurred in over 40% of migraine sufferers.)

Postdrome. After a migraine attack, there is usually a postdrome phase, in which patients may feel exhausted and mentally foggy for a while.

Cluster Headache. Cluster headaches are very painful events. Patients typically awaken a few hours after they go to sleep with the following symptoms:

Very severe, stabbing pain centered in one eye.
Excessive tearing, a drooping eyelid, and one stuffy or runny nostril, all on the same side as the pain.
Feelings of intense restlessness are common. People in the throes of a cluster headache may pace the floor or may even bang their heads against the wall in an attempt to cope with the pain.
Cluster headaches often have a cycle with the following pattern:
Attacks themselves are usually brief, lasting 30 - 90 minutes, although they can persist for up to 3 hours.
During an active period, sufferers can experience as few as one attack every other day to one or more daily. In a rare form of cluster headache, known as chronic paroxysmal hemicrania, as many as six attacks per day can occur.
An active period of recurrent cluster attacks typically extends over 4 - 12 weeks.
Headache-free periods last several months to even years.

Hemicrania Continua. Hemicrania continua is a rare form of chronic headache. Such headaches occur on one side of the face, mostly in women. The patient generally experiences continuous low-level headache with periodic attacks that can last days to weeks. (About 10% of patients experience remissions.) The actual attacks can be mild to severe, and may resemble migraines. The headaches can usually be treated successfully with NSAIDs such as indomethacin (Indocin). Migraine medications are typically not as helpful.

Prognosis

Both episodic tension-type headache and chronic daily headache affect quality of life. Tension-type headache episodes are rarely disabling, however, and rarely require emergency treatment. If they do, usually there is a migraine component occurring with the tension-type headache.

Nevertheless, although they are not medically dangerous, chronic tension headaches have a negative impact on quality of life, families, and work productivity. Several studies have reported lower quality of life with any chronic daily headache compared to those with no headaches or who have only episodic ones. In one study, people with tension-type headaches tended to have higher anxiety and lower quality of life during a headache attack than people with migraines (who, however, were less able to cope during a migraine attack).

In one study, two-thirds of patients with chronic tension-type headaches reported daily or near daily headaches for an average of 7 years. Only 12% reported headaches occurring less than 20 days a month. In the study, 74% of the patients had to take some time off from work because of the headaches, and about a third reported impaired sleep, less energy, and reduced emotional well-being on 10 or more days a month. Most were able to carry out their daily responsibilities even when in pain, although at lower than normal capacity. This and other studies report a strong association between anxiety and depression and chronic tension-type headaches.

Causes

There does not appear to be a single cause of chronic tension-type headache. Many factors are likely involved.

One of the most popular theories on the cause of tension-type headaches involves muscle contraction in the head, neck, and shoulders. There are several ideas about how muscle tension may produce these headaches.

The most common cause of tension-type headaches is muscle contraction in the head, neck or shoulders.

Studies have suggested that tension-type headache sufferers may have higher-than-average muscle tenderness in the face and head that make them more susceptible to headache after muscle contractions. A few studies suggest that some patients with chronic headaches may be overly sensitive to pain in general or may overestimate muscle contraction pain.

One theory suggests that sustained tension or stress that produces muscle contractions in the tender areas around the skull constrict blood vessels. Blood flow is reduced so oxygen is blocked and waste matter builds up, resulting in pain.

Still, pain can last long after the muscles have relaxed, and clear evidence is lacking on how or even if muscle contractions are a major cause of tension headache.

Researchers are increasingly finding evidence to support factors that are common to both migraine and tension-type headache. Some research suggests that both problems may result from a continuum of abnormalities in the central nervous system (the nerves in the brain and spine). Such changes trigger a progression of symptoms starting with mild sensations, developing into tension headache, and finally, progressing in some people to a migraine.

Dopamine, for example, may act as a stimulant of the migraine process. Some evidence suggests that certain genetic factors make people oversensitive to the effects of dopamine, which include nerve cell excitation. Such nerve-cell over-activity could trigger the events in the brain leading to migraine. The prodromal symptoms (mood changes, yawning, drowsiness), for example, have been associated with increased dopamine activity. Dopamine receptors are also involved in regulation of blood flow in the brain.

Nitric Oxide. Other research suggests that over-excitable neurons release nitric oxide, a small molecular messenger, which may be important in triggering in most primary headaches (tension-type, cluster, and migraines). Elevated levels have been observed in blood cells of patients with tension-type headache. Some evidence suggests that the release of this molecule in blood vessels may activate nerve pathways in the brain, muscles, or elsewhere and increase pain.

Estrogen Fluctuations in Women. Tension-type headaches and migraine headaches are more common in females during adolescence and adulthood. Most likely hormone fluctuations, rather than whether levels are elevated or low, trigger headaches. Some research suggests that fluctuations in estrogen levels may impact levels of serotonin and other pain-modulating substances that affect these headaches.

Genetic factors appear to play a role in predisposing people to recurrent tension headaches. One study of twins suggested that the chances of inheriting the susceptibility to recurring headaches (both migraine and tension) were about 70% in close relatives. The trait is equal in both boys and girls. Because such headaches tend to occur more in females, however, hormonal, social, psychological, or other factors must play a role in their development.

Tension-type headache has been highly associated with an intense response to stress. Some studies suggest that patients with chronic tension-type headaches have more general feelings of anxiety or depression and are less able to express their emotions. One study indicated that patients with tension headaches tend to perceive everyday events as more stressful than those without headaches. Some research even suggests that tension-type headache victims may have some biological predisposition for translating stress into muscle contraction. Still, the link between stress and tension-type headaches is not fully understood, and some evidence challenges any causal association.

Whiplash, concussions, and other head and neck injuries, even mild ones, may result in persistent tension-type or migraine headaches in both adults and children. Such headaches should be treated as if they were the primary types. The risk for tension headaches may persist for years after the injury.

Myofascial pain involves the fascia (connective tissue) and muscles. Some researchers think that tension-type headaches may be linked to myofascial trigger points in the neck and shoulder muscles. Trigger points are knots in the muscle tissue that can cause tightness, weakness, and intense pain in various areas of the body. (For example, a trigger point in the shoulder may result in headache.) Because fibromyalgia is also characterized by myofascial pain, researchers are exploring whether there may be an association between this condition and tension-type headache. [See In-Depth Report #76: Fibromyalgia.]

Medication Overuse (Rebound) Headache. About a third of persistent headaches -- whether chronic migraine or tension-type -- are medication-overuse headaches. These are the result of a rebound effect caused by the regular overuse of headache medications. Nearly any headache medication can produce this effect. In one study of headache sufferers, medication-overuse headaches developed after an average of 1.7 years of regular use of triptans (18 doses a month), after 2.7 years of ergot use (37 doses as month), and after 4.8 years using painkillers (114 doses a month). Regular use of painkillers for any chronic problem (such as arthritis) poses a 2% risk for medication-overuse headache, with risk being highest in people who already have primary headaches, especially migraines.

Chronic Migraines. In some cases, migraines naturally evolve into chronic, daily headaches referred to as transformed migraines.

About 90% of people seeking help for headaches have a primary headache. The rest are secondary headaches, caused by an underlying disorder that produces headache as a symptom. More than 300 conditions can cause headaches. Some of the most common are listed below.

Sinus Headaches. Many primary headaches, including migraines, are misdiagnosed as sinus headaches. Sinus headaches can occur in the front of the face, usually around the eyes, across the cheeks, or over the forehead. They are usually mild in the morning and increase during the day and are usually accompanied by fever, runny nose, congestion, and general debilitation. Sinus headaches spread over a larger area of the head than migraines, but it is often difficult to tell them apart, particularly if headache is the only symptom of sinusitis. They even coexist in many cases. Often, the visual changes associated with migraine can rule out sinusitis, but such visual changes do not occur with all migraines. (In rare cases, sinusitis can cause double vision and even vision loss, a sign of very serious infection.)

Headaches that Originate in the Neck. Some headaches may be caused by abnormalities of the neck muscles (called cervicogenic headaches). Nerves in the neck converge in the trigeminal nerve, which is the largest nerve in the skull. It originates in the brain stem and supplies sensation to the face. This nerve can generate pain signals to the facial area that the brain may interpret as headache. Pain is usually on one side. Even if it affects both sides of the head it is usually more severe on one side. The quality of the headache may be difficult to distinguish from an aching tension headache or a mild migraine without aura. Cervicogenic headaches can result from prolonged poor posture (such as that caused by sitting in front of a computer keyboard or driving daily for long periods), arthritis, injuries of the upper spine, or abnormalities in the cervical spine (the spinal bones in the neck).

Temporomandibular Joint Disorder. Muscle contractions that cause headaches may be a result of temporomandibular joint dysfunction (TMJ, also known as TMD), which is caused by clenching the jaws or grinding the teeth (usually during sleep), or by abnormalities in the jaw joints themselves. The diagnosis is easy if chewing produces pain or if jaw motion is restricted or noisy. TMJ pain can occur in the ear, cheek, temples, neck, or shoulders. This condition often coexists with chronic tension headache.

Click the icon to see an image of temporomandibular joint dysfunction.

Neuralgia. Neuralgia is pain due to nerve abnormalities, which can occur in the facial area and resemble migraines or sinus headaches.

Hypertension. Although many people attribute headaches to high blood pressure, evidence suggests that hypertension does not cause headaches. An exception is malignant hypertension, an uncommon medical emergency in which the blood pressure abruptly rises to extreme levels, causing damage to blood vessels in the brain, heart, and kidneys.

Epilepsy. Severe headaches that can last 12 hours or longer are very common in epilepsy. Migraine is particularly associated with epilepsy.

Risk Factors

Tension-type headaches are the most common headaches, accounting for nearly half of all headaches. According to one study, nearly 40% of Americans have at least one episode of tension headache during the course of a year. Some reports estimate that over 85% of women and about 63% of men will have a tension-type headache at some point during a year. Nearly everyone has at least one tension-type headache during their lifetime.

Surveys indicate that about 3 - 5% of the general population has chronic tension-type headache, with the prevalence being higher in women.

About 40% of people with tension-type headaches first have them before they are age 20, and another 40% first experience them between ages 20 - 40. Most of the remaining headache sufferers first have tension-type headaches in the decade between ages 40 - 50. Chronic tension-type headache tends to occur in older adults.

Headaches in Children. Headaches are rare before age 4 but increase in prevalence throughout childhood, reaching a peak around age 13. In one large study, about 7% of seven year olds and 15% of 11 year olds had headaches. Ten percent of these childhood headaches were recurrent. In many of these patients, chronic headaches persist into adulthood. In addition, as adults these patients have a tendency to develop multiple physical or psychiatric complaints, such as back pain, muscle aches, digestive complaints, and depression.

Studies have found that only a minority of chronic childhood headaches are due to physical conditions, such as head injuries or medical problems. In one study, over 62% of children with tension-type headache episodes suffered some form of emotional disorder. In the study, every child reported the presence of a stress factor.

Psychological factors associated with childhood tension-type headaches include:

Sleep problems. According to one study, more than two-thirds of children who experience chronic daily headaches suffer from sleep disturbances, especially difficulty falling asleep.
Moderate or severe depression.
Emotional rigidity in a child and more repressed anger than their peers.
Family stress. This includes maternal illness or separation, family bereavement, relationship problems, mental illness in a family member, and other stressful family events.
Problems at school. According to a National Headache Foundation survey, nearly 30% of children miss school because of headaches. For many children, the start of the school season can be a particularly stressful time.

The National Headache Foundation recommends these tips for parents:

Keep a diary of child’s headaches noting time of onset, length and intensity of attack, location of pain, and food triggers.
Make sure child gets plenty of sleep at regular times.
Avoid changes in child’s eating routing (hunger and eating at irregular times can trigger headaches).
Discuss any headache concerns with child’s doctor.

The following conditions can make people susceptible to tension-type headaches.

Chronic poor posture
Chronic overwork
Upper respiratory tract infections, such as colds and flu
Sleep disorders. Sleep problems, such as insomnia, sleep apnea, or habitual snoring, are common in all primary headaches. Headache can disturb sleep, but sleep disorders may also contribute directly to tension headache, particularly those that occur at night or early morning. (In one study, treating people who had chronic headaches for sleep apnea cured the headaches in many cases.)
Obesity
Hypothyroidism (decreased thyroid function)
Dental problems
Allergies
Substance or alcohol abuse
Temporomandibular joint dysfunction (TMJ, also called TMD). This is a condition in which there are abnormalities in the jaw joints. TMJ itself can cause headache, and it also often coexists with chronic tension headache.

Certain triggers, including the following, may cause headache episodes in people with chronic tension-type headaches:

Specific stressful events
Not eating on time
Fatigue or lack of sleep
Crying. In one study, only stress, anxiety, and menstruation were more important headache triggers in women.
Withdrawal from over-used substances (caffeine, nicotine, alcohol, pain relievers)
Eyestrain
Intense physical exertion, including sexual activity. Athletes are at higher risk for headaches. Patients with tension-type headaches should not avoid exercise, however. Ordinary levels of physical activity do not usually precipitate these headaches. Furthermore, a sedentary lifestyle may increase the risks for stress and obesity and thereby for tension headaches in susceptible people.
Certain foods, such as chocolate, cheese, and the flavor enhancer monosodium glutamate (MSG), are commonly cited as triggers for tension headaches as they are for migraines.
Medications (overuse of headache medications, nitrates, certain anti-depressants, some drugs used to treat high blood pressure, and many others.)
Hormonal changes, such as specific menstrual phases, in women.

Weather conditions, certain smells, smoke, and light, which can set off migraines, are not common triggers for tension-type headaches.

The rapid consumption of ice cream or other very cold foods or beverages is a well-known trigger of sudden headache pain -- the so-called "ice cream" headache. It can be easily prevented by warming the food or drink for a few seconds in the front of the mouth before swallowing. Drinking a glass of room-temperature water quickly relieves the pain.

Diagnosis

Extensive testing may be advised for anyone with a chronic, daily headache. Tracking times of medications, withdrawal, and headache, using the headache diary, is usually very helpful in diagnosis.

According to the International Headache Society, a diagnosis of tension-type headache is suggested by the following symptoms:

Pressing or tightening (but non-pulsating) feeling
Mild-to-moderate pain on both sides of the head
Not aggravated by routine physical activity (walking, etc.)

In episodic tension-type headaches:

No nausea or vomiting
Photophobia (intolerance of light) or phonophobia (intolerance of sound) may be absent or one of these symptoms (but not both) may be present

In chronic tension-type headaches:

No vomiting
No moderate or severe nausea
No more than one of the following symptoms: Mild nausea, photophobia, or phonophobia
Some types of chronic tension headache may include tenderness upon manual palpitation of the head (pericranial tenderness).

Differentiating Medication-Overuse (Rebound) Headache from Tension-Type Headache. About a third of persistent headaches are the result of the rebound effect caused by the overuse of headache medications (formerly called rebound headaches).

Usually in such cases, medications have been taken on an ongoing basis for more than 3 days each week. If patients stop taking these drugs, the headaches come back. The patient then starts taking the drugs again. Eventually the headache simply persists and medications are no longer effective. Even after successful medication withdrawal, relapse is common, particularly with drugs that contain caffeine, so doctors should check for this type of headache even in patients who have previously been treated.

Medications implicated in medication-overuse headache include barbiturates, sedatives, narcotics, and migraine medications, particularly those that also contain caffeine. (Heavy caffeine use can also cause this condition.) Simple painkillers, such as aspirin or ibuprofen, are less likely causes of medication-overuse headaches.

Differentiating Tension Headaches from Chronic Migraines. It is often difficult to differentiate between chronic migraine and chronic tension-type headaches. The McGill Pain Questionnaire may be useful for ruling out migraine. According to a 2003 study, patients with migraine who answer the questionnaire report significantly more severe specific symptoms (throbbing, stabbing, gnawing, hot, sickening, exhausting) than those with tension-type headaches. There is very little difference between these headaches, however, in scores of overall severity of the pain.

For an accurate diagnosis, the patient should describe the following:

Duration and frequency of headaches
Recent changes in their character
Location of the pain
Type of pain (throbbing or steady pressure)
Intensity of the headache
Associated symptoms, such as visual disturbances or nausea and vomiting. (These are seen most often with migraines.)
Behaviors during a headache. Different behaviors may help distinguish between migraine and tension headaches. People with tension headaches tend to relieve pain by massaging the scalp, temples, or the nape of the neck. People with migraines are more likely to compress the forehead and temples (tying a scarf around the head) or to apply cold to the area. They also tend to isolate themselves, lie down, induce vomiting, and use more pillows than usual. (None of these maneuvers do much good in relieving either headache, unfortunately.)

The patient should try to recall what seems to bring on the headache and anything that relieves it. Keeping a headache diary is a useful way to identify triggers that bring on headaches. Be sure to include all events preceding an attack. Often two or more triggers interact to produce a headache.

Researchers are investigating triggers of headaches to determine if certain ones are more likely to set off different primary headaches. In general, however, the same stimuli seem to trigger any of the primary headaches, although people with migraines may be more sensitive to some of them (weather, certain smells, light, and smoke) than people with tension headaches.

Tracking medications is an important way of identifying medication-overuse headache or transformed migraine.

Be sure to attempt to define the intensity of the headache. There are different scoring symptoms available that help communicate the severity of the pain to the doctor. For instance, the following is a number system that can be helpful:

1 = Mild, barely noticeable

2 = Noticeable, but does not interfere with work/activities

3 = Distracts from work/activities

4 = Makes work/activities very difficult

5 = Incapacitating

The patient should report any other conditions that might be associated with headache, including but not limited to the following:

Any chronic or recent illness and their treatments
Any injuries, particularly head or back injuries
An uncharacteristic dietary changes
Any current medications or recent withdrawal from any drugs, including over-the-counter or natural remedies
Any history of caffeine, alcohol, or drug abuse
Any serious stress, depression, and anxiety
The doctor will also need the patient's general medical and family history, particularly concerning headaches or other diseases such as epilepsy. Migraine, in particular, tends to run in families.

In order to diagnose a chronic headache, the doctor will examine the head and neck and will usually perform a neurologic examination, which includes a series of simple exercises to test strength, reflexes, coordination, and sensation. The doctor will also examine the eyes to rule out pressure build-up in the eye as a cause of headache. The doctor may ask questions to test short-term memory and related aspects of mental function.

Imaging tests of the brain may be recommended under the following circumstances:

If the results of the history and physical examination suggest neurologic problems.
For patients with headache that wakes them at night.
For new headaches in the elderly. In this age group, it is particularly important to first rule out age-related disorders, including stroke, hypoglycemia, hydrocephalus, and head injuries (usually from falls).
For patients with worsening headache.

They are not recommended for patients with migraine and with no other abnormal indications.

The following tests may be used:

A CT (computed tomography) scan may be ordered to rule out other conditions, particularly chronic sinusitis, which, in one study, occurred in 20% of patients with chronic headache. Other findings include aneurysms, benign or cancerous growths, and other abnormalities in the brain.
X-rays and other tests may also be used if sinusitis is strongly suspected.
A neck x-ray can reveal arthritis or spinal problems.
Other tests include an MRI (magnetic resonance imaging), EEG (electroencephalogram), lumbar puncture, ultrasound testing, and cerebral angiography, which are only performed if there is reason to suspect an underlying disease.

Headaches indicating a serious underlying problem, such as cerebrovascular disorder or malignant hypertension, are uncommon. (It should again be emphasized that a headache is not a common symptom of a brain tumor.) People with existing chronic headaches, however, might miss a more serious condition believing it to be one of their usual headaches. Such patients should immediately call a doctor if the quality of a headache or accompanying symptoms has changed. Everyone should call a doctor for any of the following symptoms:

Sudden, severe headache that persists or increases in intensity over the following hours, sometimes accompanied by nausea, vomiting, or altered mental states (possible hemorrhagic stroke).
Sudden, very severe headache, worse than any headache ever experienced (possible indication of hemorrhage or a ruptured aneurysm).
Chronic or severe headaches that begin after age 50.
Headaches in the back of the head accompanied by other symptoms, such as memory loss, confusion, loss of balance, changes in speech or vision, or loss of strength in or numbness or tingling in arms or legs (possibility of small stroke in the base of the skull).
Headaches after head injury, especially if drowsiness or nausea are present (possibility of hemorrhage).
Headaches accompanied by fever, stiff neck, nausea, and vomiting (possibility of spinal meningitis).
Headaches that increase with coughing or straining (possibility of brain swelling).
A throbbing pain around or behind the eyes or in the forehead accompanied by redness in the eye and perceptions of halos or rings around lights (possibility of acute glaucoma).
A one-sided headache in the temple in elderly people; the artery in the temple is firm and knotty and has no pulse; scalp is tender (possibility of temporal arteritis, which can cause blindness or even stroke if not treated).
Sudden onset and then persistent, throbbing pain around the eye possibly spreading to the ear or neck unrelieved by pain medication (possibility of blood clot in one of the sinus veins of the brain).

Managing Tension-Type Headaches

Given the very high prevalence of tension-type headaches, some experts express frustration over the lack of serious scientific attention given to this problem. Unfortunately, few tension headache sufferers seek medical help for their problem, and 60% of those with severe headaches use only over-the-counter medications. Many patients fear that they will not be taken seriously by their doctor or believe the widespread misperceptions that their problem is due solely to stress. With medications, relaxation training, lifestyle changes, and other therapies, over 90% of patients can be helped.

Fortunately, most acute tension-type headaches get better without any treatment, and simple over-the-counter pain relievers such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs) can treat mild symptoms.

The most common pain relievers are:

Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol)
Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail)

Acetaminophen may be effective for moderate-to-severe headaches only at high doses (1,000 mg), while NSAIDs can be effective at lower doses. One study indicated that ibuprofen and naproxen were more effective than aspirin or acetaminophen.

There are few proven therapies for treating or preventing chronic tension-type headaches, and studies are weak. To date, the major treatments used for chronic tension-type headache are a group of antidepressants called tricyclics, and cognitive-behavior therapy. Used alone either of these approaches achieves modest benefits, at best. A combination, however, may be very helpful in some cases.

Some research suggests the following steps in treating this condition:

Because many chronic daily headaches are due to over-use of headache medications, withdrawal from such drugs is the first action. (NSAIDs or other painkillers should not be used to prevent chronic tension-type headaches.)
Cognitive behavioral therapies, including relaxation and stress-reduction techniques, should be used next for managing headaches. They should be the first option for children and adolescents with chronic headaches.
If medication withdrawal and psychological methods fail to bring improvement, tricyclic antidepressants are tried next in combination with cognitive therapy.
Physical therapy, massage therapy, or acupuncture may help some people.

If headaches develop because of medication overuse, the patients cannot recover without stopping the drugs. (If caffeine is the culprit, a person may only need to reduce coffee or tea drinking to a reasonable level, not necessarily stop drinking it altogether.) The patient usually has the option of stopping abruptly or gradually and should expect the following course:

Most headache drugs can be stopped abruptly, but the patient should be sure to check with the doctor before withdrawal. Certain non-headache medications, such as anti-anxiety drugs or beta-blockers, require gradual withdrawal.
If the patient chooses to taper off standard headache medications, withdrawal should be completed within three days or shorter. Otherwise the patient may become discouraged.
No matter which approach is used for stopping medication, the patient must expect a period of worsening headache for a few days afterward. Alternative pain relievers may be administered during the first days to help withdrawal.
Most people feel better within 2 weeks, although headache symptoms can persist up to 16 weeks (and in rare cases even longer).

Studies suggest that nearly half of patients with medication-overuse headaches relapse. According to one study, the relapse rate may be much higher for tension headaches (73%) than for migraine headaches (22%). More research is needed to determine the optimal methods for drug withdrawal. On the encouraging side, some patients experience dramatic long-term relief from all headaches afterward.

Medications

The standard treatments for tension-type headaches are non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, and tricyclic antidepressants, usually amitriptyline (Elavil, Endep).

Several pain relievers are helpful for mild-to-moderate headaches. They should not be used to prevent headaches, however.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). NSAIDs are common pain relievers that block prostaglandins, substances that dilate blood vessels and cause inflammation and pain. NSAIDs are usually the first drugs tried for almost any kind of headache. There are dozens of NSAIDs. Aspirin is the most common, but it is not as effective for acute tension-type headache as other NSAIDs. Common NSAIDs include:

Over-the-counter NSAIDs. Aspirin, ibuprofen (Motrin), naproxen (Aleve), ketoprofen (Actron, Orudis KT)
Prescription NSAIDs. Diclofenac (Voltaren, Cataflam, Solaraze), tolmetin (Tolectin), indomethacin (Indocin)

Patients should be aware that long-term use of high-dose NSAIDs may increase the risk for stomach bleeding and heart problems, including heart attack and stroke.

Acetaminophen. Acetaminophen (Tylenol) is a good alternative to NSAIDs when stomach distress, ulcers, or allergic reactions prohibit their use. A high dose (1,000 mg), however, is needed for this drug to be effective for headaches. Midrin (a combination of a drug that narrows blood vessels, a mild sedative, and acetaminophen) may be very helpful for tension-type headaches.

Acetaminophen does have some adverse effects, however, and the daily dose should not exceed 4 grams (4,000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. Acetaminophen may cause serious kidney problems in people who already have kidney disease. It also may interact with certain medications, including the blood thinner warfarin.

Antidepressants known as tricyclics are most often used for prevention of severe chronic tension-type headaches. Newer selective serotonin-reuptake inhibitors (SSRIs) antidepressants are also sometimes used in milder cases.

Tricyclic Antidepressants. Tricyclics are not only useful for depression but also appear to help relieve muscle pain and improve sleep. They are sometimes classified in one of two categories: tertiary or secondary amines:

Tertiary amines include amitriptyline (Elavil) and imipramine (Tofranil). Amitriptyline is the tricyclic most commonly used for tension-type headache. These drugs tend to cause more drowsiness than secondary amines, which may be helpful for patients with sleep problems.)
Secondary amines include desipramine (Norpramin) and nortriptyline (Pamelor, Aventyl). Secondary amines may have fewer side effects than tertiary amines, but they are just as toxic in high amounts.

Unfortunately, these drugs can lose effectiveness over time. Side effects are also fairly common with these medications. Drowsiness is the most common, but may vary by specific drug. In addition, side effects most often reported include dry mouth, constipation, blurred vision, sexual dysfunction, weight gain, trouble urinating, heart rhythm problems, and dizziness. Blood pressure may also drop suddenly when sitting up or standing.

Tricyclics can have serious, although rare, side effects, including heart rhythm problems, which can be dangerous for some patients with certain heart diseases. These drugs can be fatal with overdose.

Selective Serotonin-Reuptake Inhibitors. Selective serotonin-reuptake inhibitors (SSRIs) work by increasing levels of serotonin in the brain. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa). Because they act on serotonin specifically, they have fewer side effects than the older antidepressants, such as monoamine oxidase inhibitors (MAOIs), which affect a number of chemicals in the body. SSRIs take 2 - 4 weeks to be effective in most adults and sometimes longer, up to 12 weeks, so their value for treating headaches is limited.

Side effects may include nausea, stomach problems, agitation, insomnia, mild tremor, impulsivity, temporary weight gain or loss, and sexual dysfunction. Death from overdose is extremely rare. Serious interactions can occur with other antidepressants, such as tricyclics and MAOIs.

Designer Antidepressants. Several drugs target other neurotransmitters, such as norepinephrine, alone or in addition to serotonin, and are showing promise for prevention of tension-type headache. The following are some examples:

In one study, bupropion (Wellbutrin) was as effective as a tricyclic in preventing tension-type headaches.
Nefazodone (Serzone), a fast-acting designer antidepressant, was particularly beneficial in a study of patients with chronic daily headaches. After 3 months of treatment, symptoms were reduced by half in over 70% of patients. Nearly 60% of them said their symptoms improved over 75%.
Venlafaxine (Effexor), a designer antidepressant that targets both serotonin and the brain chemical norepinephrine, is showing promise for preventing chronic tension-type headaches (as well as migraines). In one study, patients who took the extended-release form of the drug for 6 months went from an average of 24 tension headaches a month to 15.
Mirtazapine (Remeron) is a unique antidepressant known as a 5-HT2 blocker. It may indirectly enhance the affects of both serotonin and norepinephrine. In one study, it was as effective in treating chronic tension-type headache as the tricyclic Elavil. Mirtazapine has significantly fewer side effects than tricyclics, although it may slightly raise cholesterol and triglyceride levels. It may also cause blurred vision and slight weight gain.

Mild anti-anxiety drugs are occasionally used as an adjunct in treating chronic headaches to decrease muscle contraction or to calm anxiety symptoms during periods of extreme stress. They include alprazolam (Xanax) and clonazepam (Klonopin). They tend to be highly addictive, however, and patients should therefore use them only on a short-term basis.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea, but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these drugs.

Opioids. Opioids, such as codeine or hydrocodone, are sometimes prescribed for severe headaches, although their use is controversial because of the risk for addiction. Methadone is showing promise for patients who do not respond to standard treatments. These drugs are narcotics, however, and may be subject to abuse. Patients must be monitored and reevaluated regularly. Overuse of these drugs can reduce their effectiveness and lead to medication-overuse headaches, so it is important for a doctor to supervise this type of medication. Long-term, high-dosage use of some of these drugs can also lead to kidney disease and ulcers. Other, less serious side effects include gastrointestinal upset, dizziness, and ringing in the ears (tinnitus).

Sedatives. Barbiturates, particularly butalbital (Butalan) and its combinations (Fioricet, Axocet), are occasionally prescribed if other medications fail to provide relief. These drugs are sedatives that also contain pain relievers. Because they pose a very high risk for alcohol-like intoxication, dependence and drug-induced headaches during withdrawal, they should be used very sparingly. Some experts believe they should not be used at all for headaches.

Valproate. In some studies, the anticonvulsant medication valproate has been effective for stopping headaches in some patients with persistent migraines and tension-type chronic daily headaches. In one study, 75% of patients with either type of headache experienced at least a 50% reduction in headache frequency and severity. Minor side effects occurred in a third of the patients. Other anti-seizure medications are under investigation.

Botulinum Toxin. Botulinum toxin A (Botox) injections are now widely used to relax muscles and reduce skin wrinkles. They are also being investigated for chronic daily headaches, which include tension-type headache. This potentially deadly toxin is very safe when tiny amounts are injected into small muscles. In a 2003 study of various headache types (including tension-type headache), over 85% of all the patients had fewer headaches per month and the intensity of the pain. Several 2005 studies reported that Botox injections every 3 months might help patients with chronic daily headaches have fewer headaches. However, other studies have reported no benefit. Botox is not approved for headache treatment.

It should be noted that Botox also causes headaches in about 1% of cases. In some cases, the headaches can be very severe and long lasting (from 8 days to a month). Some researchers suggest that either a contaminated batch of Botox or a specific injection technique may be the cause, but additional investigation is needed.

Tizanidine. Tizanidine (Zanaflex) is a muscle relaxant that is emerging as a possible effective preventive drug in chronic tension-type headaches. Called an alpha2-adrenergic agonist, it blocks the release and effectiveness of a stress chemical in the body called norepinephrine and may also help prevent muscle spasms. Studies have reported that nearly 70% of patients with chronic tension-type headaches experienced a reduction in headache symptoms of 50% or more. It also appears to help patients experiencing medication-overuse headache to withdraw from medications. Side effects are usually minor and include fatigue and dry mouth, although patients taking the drug need to be monitored periodically for potential liver damage.

Nitric Oxide Synthase Inhibitors. Nitric oxide synthase inhibitors block nitric oxide, which may play a role in increasing nerve activity that leads to headache. Drugs being investigated include L-NG methyl arginine hydrochloride (L-NMMA) and L-NG-nitro-arginine. Studies suggest they may be very helpful in reducing chronic tension-type pain.

Treatment

In cases where abnormalities or injuries in the cervical spine (the spinal bones in the neck) cause headaches, a cervical epidural nerve block may be beneficial in treating and preventing further pain. This procedure involves injecting small amounts of a corticosteroid and anesthetic into spaces between the vertebrae in the neck to block the nerves. Some patients have reported significant pain relief from this procedure.

Dental Adjustment. Some reports suggest that dental adjustment to help teeth bite down evenly might help some people with temporomandibular joint disorder and chronic headaches. The results indicated that dental adjustments may be helpful. A systematic review in 2003, however, reported no headache relief from this approach.

Nociceptive Trigeminal Inhibition. A dental device called the NTI (nociceptive trigeminal inhibition) tension suppression system has been approved for relief of headaches due to jaw clenching during the night. The small plastic mouthpiece is fitted by a dentist and slips over the two front teeth, preventing teeth clenching at night. Preliminary studies report some benefits for relief of migraines and associated tension-type headaches.

Techniques using acupuncture points on the body have become popular for managing pain. Studies do show some benefits.

Standard Acupuncture. A major 2001 analysis of 26 trials of acupuncture suggested that it may have some benefit for tension headache, but the evidence to date is not completely convincing. Some studies comparing short-term acupuncture to sham (dummy) procedures report no benefits. A 2005 study suggested that acupuncture may help tension-type headache, but needling at non-acupuncture points worked just as well. This suggests a placebo effect may account for the headache relief experienced by acupuncture patients.

Acupuncture, hypnosis and biofeedback are all 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.

Percutaneous Electrical Nerve Stimulation. A technique called percutaneous electrical nerve stimulation (PENS) uses low-level electrical pulses delivered through acupuncture needles into soft tissue. Patients are barely aware of the sensation. Some studies are showing some benefits, but strong evidence is still lacking to confirm or refute its benefits.

Acupressure. One acupressure practitioner reports that pressing for 60 seconds on the web space between the forefinger and thumb of the dominant hand erases headache in patients with migraine and tension-type headaches. The specific spot pressed should be the most tender point in the web area. The patient should then lie down for about 15 minutes.

Two investigational procedures called automated or electrical twitch obtaining intramuscular stimulation (ATOIMS or ETOIMS) are showing promise. ATOIMS uses an automated mechanical device that vibrates the muscle using a tiny pin. (The sensation is described as similar to a mosquito bite.) ETOIMS uses an extremely mild electrical current. They can also be used together. Both approaches cause the muscles to twitch and relax, and then the process is stopped. Discomfort is minimal. Small studies are reporting some help in relieving a number of conditions that cause chronic pain, including tension headache.

Spinal manipulation by chiropractors or osteopaths may have some benefits for preventing tension-type headaches. Evidence is stronger on benefits of spinal manipulation for patients with headaches originating from nerve or muscular problems in the neck. Some researchers believe that tension-type headaches relieved by spinal manipulation are probably really caused by neck problems.

In a small 2006 study, daily relaxation exercises combined with three sessions of osteopathic treatment helped reduce the frequency -- but not the intensity -- of tension-type headaches. Another 2006 study suggested that physical therapy that incorporates a craniocervical (head and neck) training program may help reduce tension-type headache frequency, intensity, and duration as well as reduce the need for pain medication. In the 6-week program, patients performed 10-minute exercises twice a day. The exercises were designed to retrain muscles in the head, neck, and shoulders. The benefits of these exercises lasted up to 6 months after the program had ended.

Lifestyle Changes

Good health habits -- including adequate sleep, healthy diet, regular exercise, and good stress management -- are important, along with the following specific measures for headache management. Quitting smoking is essential in reducing the risks for all headaches.

An ancient and potentially effective remedy for tension headaches uses pressure applied to the head (such as a headband or a towel wrapped around the head) plus either heat or cold. In one study, 87% of headache sufferers experienced significant relief, and the rest reported moderate relief while they were wearing special headbands that could be tightened. They applied packs that were frozen or heated in a microwave. (Either heat or cold packs were useful, although people with tension headaches generally preferred cold packs.)

A healthy diet rich in fresh fruits and vegetables and whole grains and low in saturated fats (animal fats) is important to everyone. Fish (particularly oily fish, such as salmon and tuna) and soy are protein sources that may be a good alternative to red meats.

Caffeine. In some people with headaches, caffeine appears to be an excellent companion to medications. One study found that the caffeine equivalent of two and a half of cups of coffee can help treat a tension-type headache by itself. Many medications contain combinations of pain or anxiety relievers and caffeine, which boosts pain-relieving potency and counters drowsiness. Taking ibuprofen along with caffeine is even more effective than either substance alone. (It should be noted that in some people with migraines, the tannin found in coffee or tea may be a trigger for the headache. In addition, withdrawal from caffeine is a major cause of headache.)

Headaches that occur during the night and early morning may be related to sleep disorders. One study reported that treating an underlying sleep disorder, such as sleep apnea or insomnia, in patients who also had headaches resulted in headache cure or improvement in all patients except those who suffered from restless legs syndrome.

Several stress-reduction methods are available that may help counteract the tendency for muscle contraction and uneven blood flow associated with some headaches. Such approaches may be especially helpful for children and pregnant women with chronic headaches. (For information on acupuncture and spinal manipulation, see the Treatment section of this report.)

Among the stress reduction techniques that may be helpful are:

Guided imagery. (This uses body awareness and visualization of pleasant or positive images.)
Biofeedback. This technique works when patients develop awareness of their physical responses and learn to feed this information back to the brain for the purpose of replicating that response. It is often used to reduce muscle tension. One interesting and sometimes effective technique for headaches is called thermal biofeedback. It is based on the concept that hand-warming reduces blood flow to the brain and so relieves headache. The patient learns techniques (such as using specific images) that can raise the temperatures of the hand during a headache. Studies suggest the approach has been helpful in children with tension and migraine headaches.
Autogenic training. This approach combines elements of meditation, relaxation, and self-hypnosis. In one study, it reduced headache frequency and use of medications in patients with tension-type and migraine headaches. It was more successful for tension-type headache.
Massage therapy. In one study, massage therapy of the neck and shoulder muscles reduced the frequency of chronic daily tension-type headaches within the first week of treatment. (It did not have any effect on the intensity of headaches, however.)
Reflexology, an alternative massage method that manipulates the feet, was associated with improvement in 81% of patients with tension or migraine headaches. Patients reported an improvement in energy, well-being, and increased ability to understand the cause of the headaches. In the study, 19% went off medication.
Muscle relaxation exercises.
Self-hypnosis.
Breathing exercises. Studies have reported that correct and rhythmic breathing from the diaphragm can sometimes relieve tension-type headaches. Such breathing exercises may be particularly beneficial when performed with physical movements. (Yoga, in fact, is a practice that combines both and has been helpful in people with headaches.)

Any of these therapies may be used in conjunction with drug therapy.

Numerous herbal remedies are promoted for tension-type headache. It is important that anyone taking herbal or so-called natural remedies be aware of the lack of regulations governing their quality and effectiveness.

Essential Oils. Some patients find relief using two drops of peppermint, eucalyptus, or lavender oil added to one cup of water. The patient soaks a cloth in the solution and applies it as a compress to the head.

Herbs. Generally, manufacturers of herbal remedies and dietary supplements do not need approval from the Food and Drug Administration (FDA) 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 headache:

Feverfew is the most studied herbal remedy for headaches. It does appear to help some people. However, like all effective headache remedies, long-term use can cause a rebound effect. Some experts recommend purchasing feverfew in dried leaf form. Feverfew is generally safe, but side effects can be distressing, particularly canker sores in the mouth (5 - 15% of cases) and stomach distress. Pregnant women or women hoping to become pregnant should not take this herb. People with any blood-clotting disorders should not take it.
Valerian has sedative qualities and is listed on the FDA's list of generally safe products. However, its effects can be dangerously increased if it is used with pharmaceutical sedatives. High doses of valerian can cause blurred vision, excitability, vivid dreams, and changes in heart rhythm.
Comfrey is an herbal remedy used to treat several inflammatory problems. Evidence suggests that comfrey is toxic to the liver. Animal studies have reported a possible cancer risk. It is banned in several countries.

Resources

www.headaches.org -- National Headache Foundation
www.americanheadachesociety.org -- American Headache Society
www.aan.com -- American Academy of Neurology
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.i-h-s.org -- International Headache Society

References

Anderson RE, Seniscal C. A comparison of selected osteopathic treatment and relaxation for tension-type headaches. Headache. 2006 Sep;46(:1273-80.

Fernandez-de-Las-Penas C, Alonso-Blanco C, Cuadrado ML, Gerwin RD, Pareja JA. Myofascial trigger points and their relationship to headache clinical parameters in chronic tension-type headache. Headache. 2006 Sep;46(:1264-72.

Fernandez-de-Las-Penas C, Cuadrado ML, Pareja JA. Myofascial trigger points, neck mobility, and forward head posture in episodic tension-type headache. Headache. 2007 May;47(5):662-72.

Lenaerts ME, Gill PS. At the crossroads between tension-type headache and fibromyalgia. Curr Pain Headache Rep. 2006 Dec;10(6):463-6.

Stovner Lj, Hagen K, Jensen R, Katsarava Z, Lipton R, Scher A, et al. The global burden of headache: a documentation of headache prevalence and disability worldwide. Cephalalgia. 2007 Mar;27(3):193-210.

van Ettekoven H, Lucas C. Efficacy of physiotherapy including a craniocervical training programme for tension-type headache; a randomized clinical trial. Cephalalgia. 2006 Aug;26(:983-91.

Zissis NP, Harmoussi S, Vlaikidis N, Mitsikostas D, Thomaidis T, Georgiadis G, et al. A randomized, double-blind, placebo-controlled study of venlafaxine XR in out-patients with tension-type headache. Cephalalgia. 2007 Apr;27(4):315-24. Epub 2007 Mar 7.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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