Depression

Highlights

Antidepressants and Young Adult Suicide Risk

Postpartum Depression

First-time mothers have a high risk of developing postpartum depression during the first 3 months following birth, especially the first 10 – 19 days.

Pregnancy and Antidepressant Medication

Treatment-Resistant Depression

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).

Forms of depression
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. See In-Depth Report #66: Bipolar disorder.

Major Depression

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:

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:

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 (Chronic 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.

Atypical Depression

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

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, a tendency to overeat (particularly carbohydrates) and to 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.

Genetic Factors

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.

Biologic Factors

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.

Endocrine glands
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. [See Box: Depression in Women.]

Insomnia and Sleep Disorders

Studies estimate that 20% of people with insomnia suffer from major depression and 90% of people with depression have 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 actually be a symptom of later emotional disorders in some cases.

Depression as Adaptive Strategy

Some experts theorize that low mood is an adaptive response to situations in which expectations fail to match achievements (such as with an unrequited love affair, career failure, or a challenge of authority). In its healthy state, the pain this response causes provides both an incentive to disengage and a passive, withdrawn state that allows a period of thought before changing direction. Depression as a disorder (characterized by pervasive pessimism, low self-esteem and total lack of initiative) may develop if there are constant unachievable objects or goals and there are no positive relationships to help a person change direction. Such a theory does not, however, rule out biologic or other factors that can contribute to depressive disorders.

Depression in Women

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 between the ages of 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. [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. In one study, more than half of perimenopausal women were diagnosed with major depression. Women who had depression before menopause may also have a risk for entering the premenopausal period at a slightly earlier age than women without depression.

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 and Pregnancy

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. A 2001 study found that depression during pregnancy was more common than depression after pregnancy, with the highest depression scores occurring in week 32.

Prenatal depression can affect a mother's sleep, physical activity, adherence to care, and appetite -- all of which can affect the unborn child. Some research suggests that depression during pregnancy may pose a risk for later language and behavior problems in the child later on.

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 to be signs of postpartum depression unless they persist in severe form nearly every day for more than 1 - 2 weeks.

A 2006 study in the Journal of the American Medical Association reported that 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 between 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 breastfeeds
  • 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

Treatment During and After Pregnancy. 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, according to an important 2006 study, women with depression who stop taking antidepressants during pregnancy are five times more likely to have a relapse of depression during pregnancy than women who continue to take their medication. Experts recommend that women who are pregnant or thinking about becoming pregnant should not stop taking antidepressants without first talking to their doctors.

To complicate matters, recent research suggests that 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.

Additional 2006 studies suggested that SSRIs may cause complications if taken later in pregnancy. One study reported that persistent pulmonary hypertension (PPH), a serious lung condition, was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week of pregnancy, compared to mothers who did not take antidepressants. Another study indicated that babies may experience drug withdrawal symptoms if their mothers take SSRIs during the third trimester. Venlafaxine (Effexor), a dual inhibitor antidepressant, has also been associated with birth complications when taken during the last trimester.

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.

Risk Factors

According to a major surveys, more than 13% of Americans experience 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.

Gender and Depression

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 box: 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:

Depression and men
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.

Age and Depression

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.

Social Status and Economic Considerations

The role of society and economics has specific implications for women. [See box: 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:

Family History

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.

Consequences of Loss and Trauma

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.

Accompanying Medical Disorders

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. Thyroid disease can cause depression; however, it may be misdiagnosed as depression and go undetected.

Headaches. 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.

Stroke. Having a stroke increases the risk of developing depression.

Medications

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.

Smoking

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.

Anxiety Disorder

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.

Personality Characteristics and Disorders

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:

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

Insomnia and Sleep Disorders

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.

Risk Factors for Seasonal Affective Disorder

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. Approximately 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.

Risk for Suicide

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, and in the U.S. and 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.]

Effect on Physical Health

Major depression in the elderly or in people with serious illness seems to reduce their survival rates, even independently of any accompanying illness. In one study, even minor depression was associated with a higher risk for a shorter life in men (although not in women). Decreased physical activity and social involvement certainly play a role in the association between depression and illness severity. Some research also suggests, however, that depression produces biologic factors, such as low serotonin levels, which trigger stress-related responses in the body that cause blood clotting problems, inflammation, and damage to organs and cells.

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 increases the incidence and severity of heart attacks, stroke, and death after these events. Depression is also associated with mental decline in older people.

Depression and heart disease
Studies are now showing that depression may contribute to heart disease.

Click the icon to see a depiction of stroke.

Obesity. Both obesity and depression are increasing in Americans. In a 2002 study, for instance, adolescents who were depressed had a high risk for obesity. Conversely, a 2006 study suggested that 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. A 2002 study reported a worse outlook in cancer patients with a history of depressive symptoms -- but not in patients whose depression occurred after the illness.

Impact on Daily Activities and Relationships

Effects of Parental Depression on Children. Depression in parents can have profound effects on their children. It not only increases the risk for depression in their children, but, according to one study, it may even increase a child's risk for many medical conditions (urinary and genital disorders, headaches, lung problems).

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. Major depression, according to a major 2003 survey, accounts for nearly half of the nation's excess lost productive time (in most cases because of reduced performance at work). 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.

Substance Abuse

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:

Screening Tests

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, 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.

Ruling Out Grief and Loneliness

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:

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, an important 2003 study reported that even when depression is diagnosed, only about 20% of Americas with major depression receive adequate treatment. Most patients are treated by their family doctor, who may not have sufficient information or training on dosages or specific drugs that would be best suited for individual cases. Even worse, about half of people with depression, particularly the elderly, do not receive any therapy at all. Lack of health insurance is a major factor in these low treatment rates.

Patients with Major Depression. Numerous studies support a combination of cognitive behavioral therapy (CBT) plus antidepressants (typically an SSRI, such as Prozac) given for at least 60 days. CBT is used to resolve any residual symptoms after medication has been started. Some studies estimate that only 40% of people with chronic depression respond to medications alone compared to 60% who are given combination treatment.

For those who fail medications and psychotherapy, other techniques, such as electroconvulsive therapy (ECT), are safe and effective. In recent years, experimental procedures, such as vagus nerve stimulation and 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. However, according to several important 2006 studies, 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 less than 2 years) may respond well to watchful waiting and supportive care. For example, one study found that newer antidepressants were only modestly helpful in older patients with mild depression. Supportive care that consists only of brief and occasional counseling sessions with the family doctor may be as helpful as antidepressants in some cases.

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.

Choosing a Therapist

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:

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:

Tips for Selecting a Therapist:

Depression in the Elderly

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, Interestingly, in this regard, one study suggested that pessimistic elderly people are less prone to depression than their optimistic peers -- possibly because pessimists are more likely expect and therefore adapt to negative experiences than those with an optimistic personality.

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:

Physical and Mental Consequences of Depression in the Elderly

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. A 2000 study indicated that 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). A 2001 study, for example, reported an association between depression and a greater risk for death from heart problems even in people without a history of heart disease. A 2002 study reported a higher risk for heart failure in women -- although not in men -- with depression. However, simply treating depression does not improve survival rates after a heart attack --only treating heart disease does this.

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.

Stroke. Depression has also been linked to a higher risk for having a stroke and lower survival rates after one. In a 2000 study, patients with severe depression had a 73% higher risk for stroke, and those with moderate depression had a 25% higher risk than average. The risk for stroke in depressed African-Americans in the study was notable, 160% higher than average. Furthermore, a 2001 study confirmed that self-reported negative mood symptoms correlated with increased mortality up to 2 years after a stroke. Some research suggests that injuries in the brain after a stroke can cause depression.

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.

Osteoporosis. Some studies have linked past and current major depression with bone-density loss in women. One explanation for this association is that depressed women have higher levels of the stress hormone cortisol, which may contribute to bone density loss.

Treating Depression in the Elderly

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. A 2006 study of patients over age 70 indicated that the best way to prevent relapse is to continue antidepressant drug therapy for at least 2 years after the patient becomes symptom-free.

The use of antidepressants in the elderly is problematic:

Depression in Children and Adolescents

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:

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 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.

Consequences of Depression in Children and Adolescents

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:

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.

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

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 attributed to the increased use of antidepressants in this population. However, recent evidence has indicated that antidepressants can indeed raise the risk for suicidality (suicidal thoughts and behavior). Children and adolescents 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 Treatment section.]

Treating Depression in Children and Adolescents

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. Children and adolescents with mild-to-moderate depression should receive psychotherapy before medications are tried. Cognitive therapy may be the best approach for children and adolescents with depression. (It may even be helpful in preventing depression in young people whose parents have a history of 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 the SSRI antidepressants 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 to be 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 increased risk for suicidal behavior as well as the lack of any evidence supporting the drug's efficacy in pediatric patients.

For optimal results, SSRIs should be combined during the early acute phase with a mixture of psychotherapies, including cognitive-behavioral, interpersonal, and psychodynamic therapies. A 2004 study of adolescents with depression reported that combination treatment with fluoxetine and cognitive behavioral therapy was more effective than either treatment alone. Initial drug treatments should continue for at least 6 months, and a maintenance phase should last another year or longer.

The FDA is preparing a medication guide on the use of antidepressants in children and adolescents. Preliminary guidelines include the recommendation that caregivers and doctors be vigilant for any signs of suicidal intent or behavioral changes, particularly during the early phases of treatment, and that patients should see their doctor regularly after initiating drug therapy. [For more detailed information, see Suicide Risk and Antidepressant Medications.]

Antidepressants and Drug Treatment Guidelines

Major Classes of Antidepressants and General Treatment Guidelines

Major classes of antidepressants include:

A great deal of leeway exists in choosing an appropriate antidepressant. Overall, they seem to be equally effective, although cost, individual responses, and side effects vary widely.

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

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:

In one study, 41% of patients relapsed after they stopped treatment compared to only 18% who had continued their antidepressants. Patients, then, 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 gradual, 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 his or her 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:

Suicide Risk and Antidepressant Medications

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 associated with 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 December 2006, the FDA announced plans to update the labels of antidepressant medications to include additional warnings about the risk of suicidal thoughts and behavior in young adults (ages 18 - 25).

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:

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

Research continues on antidepressant medications’ suicide risk for adults. It appears that drug-related suicide risk may be age-dependent with the risk decreasing as people age. At this time, the FDA recommends that adults who receive antidepressants follow the standard warnings included with antidepressant medications. Adults should be observed for increased depression or suicidality during the first few months of treatment or following a change in medication dosage. Patients should immediately contact their doctor if depression symptoms worsen or if suicidal thoughts or behavior increase.

Selective Serotonin-Reuptake Inhibitors

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, Asimia, Seroxat), fluvoxamine (Luvox), citalopram (Celexa, Cipramil), and escitalopram (Lexapro, Cipralex). 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:

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 experts recommend withdrawing from medication after a year. If depression recurs, then the patients should go back on the antidepressants.

Side Effects of SSRIs. Side effects may include:

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. Reducing the dose of the antidepressant before stopping it is recommended.

Designer Antidepressants

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 do share some side effects, including dizziness and dry mouth, with other antidepressants. Comparison studies are needed, however, to determine if any of these drugs are superior to standard SSRIs in treating different stages or aspects of depression.

Dual Inhibitors. Dual inhibitors act directly on two neurotransmitters -- norepinephrine and serotonin. On the basis of a review of the literature, in 2002 an expert panel concluded that simultaneous targeting of both serotonin and norepinephrine was currently the optimal approach for patients who failed standard antidepressant therapies.

Other Antidepressants with Effects on Multiple Neurotransmitters.

Selective Noradrenaline Reuptake Inhibitor. Reboxetine (Edronax, Vestra) is at least equal to fluoxetine in reducing depression and improving social functioning, but it has many side effects including insomnia. Reboxetine is available in many countries, but not the United States.

Tricyclic Antidepressants

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

Tricyclics are sometimes grouped into two categories:

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.

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:

Tricyclics can have serious, although rare, side effects:

Monoamine Oxidase Inhibitors (MAOIs)

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 prove ineffective.

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:

Side Effects. MAOIs commonly cause the following side effects:

Azapirones

Azapirones, including buspirone (BuSpar) and gepirone (Ariza, Variza), act on serotonin receptors called 5-HT(1A). Buspirone is primarily used to treat anxiety disorders, but they may have benefits for depression -- particularly gepirone in extended release formulations. Studies on gepirone indicate that it may help some people with major and atypical depression. Buspirone (BuSpar) has shown benefits in treating resistant depression when added to the SSRIs citalopram or fluoxetine. More research is needed to determine the role of these drugs in depression.

Augmentation Strategies

Augmentation strategies generally involve the use of drugs not typically thought of as antidepressants in combination with a standard antidepressant. Such strategies are being used for patients who fail standard therapies or who need to quickly speed up the response of the antidepressant. Augmentation therapies include:

Investigational Drugs

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.

Cognitive Behavioral Therapy

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:

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.

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.

Interpersonal Therapy (IPT)

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.

Supportive Psychotherapy or Attention Intervention

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. A 2000 study reported that it was as effective as other therapies for depressed adolescents.

Problem Solving Therapy

Problem solving therapy trains patients to address current problems by breaking them into smaller manageable parts. They then identify the steps they should make toward positive change. It involves six individual sessions, and some evidence suggests it is as effective as medication in some patients with major depression.

Other Treatments

Electroconvulsive Therapy

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 to be the best treatment for severe depression. It is especially effective for patients with severe depression who experience delusions and hallucinations. Maintenance ECT may also help prevent relapse. In a 2000 study, continued use of ECT in responsive patients, along with long-term antidepressant use, prevented relapse in 73% of patients after 5 years compared to 18% in patients on antidepressants alone.

Candidates for ECT. About 40,000 Americans receive ECT each year. Many are elderly women who are psychiatric inpatients. Many experts urge that ECT be used earlier in the course of major depression, although most insurers or HMOs will not pay for early treatment. ECT may be beneficial for the following patients with severe depression:

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

This procedure is associated with a great deal of anxiety and the patient should be reassured. One form of ECT called right unilateral ECT (RUL ECT) may provide equal therapeutic benefits to more traditional bilaterally applied forms of the therapy, and more importantly, may have a less potentially deleterious effect on memory.

Side Effects. Side effects of ECT may include temporary confusion, memory lapses, headache, nausea, muscle soreness, and heart disturbances. Administering the drug naloxone immediately before ECT may help reduce its adverse effects on concentration and some (but not all) memory impairment. Concerns about permanent memory loss appear to be unfounded. One study that used brain scans before and after ECT found no evidence of cell damage. In another small study of teenagers who had undergone ECT for severe mood disorders, only 1 of 10 reported memory impairment more than 3 years after the treatment.

Phototherapy

Phototherapy is recommended as the first-line treatment for seasonal affective disorder (SAD).

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, the depression is probably caused by other factors.)

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.

Cingulotomy

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.

Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) employs high frequency magnetic pulses that target affected areas of the brain. The intention is similar to electroconvulsive therapy (ECT) but, unlike ECT, it is more precise and has the potential of having the same benefits as ECT. A 2001 review reported that it was superior to sham treatments, although it was not clear whether benefits were significant. Investigators continue to try various techniques that might produce consistent improvements.

Vagus Nerve Stimulation

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 patient may also pass a magnet over the device to give it an extra dose if they sense a seizure coming on.) 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.

Treatment of epilepsy
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.

Acupuncture

Some evidence suggests that acupuncture may help in relieving depression in some women. Small studies, including one in 2001, have found it comparable to medications or psychotherapy. Larger studies are required to confirm its benefits.

Sleep Deprivation

Research suggests that even one night of total sleep deprivation can reduce depression 40 - 60% of the time. Improvement in mood generally occurs during the night or on the following day. About 10 - 15% of people who respond to this treatment have reduced depression only after fully sleeping again. Some people may respond to sleep deprivation that occurs only in the second half of the night (3 - 6 a.m.). However, in 2 - 7% of cases depression may worsen after sleep deprivation.

Lifestyle Changes

St. John's Wort and Other Herbal Remedies

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.

St. John's Wort
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:

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.

Herbs and Supplements

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.

The following are special concerns for people taking natural remedies for depression:

  • St. John's wort. 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. St. John's wort can increase sensitivity to sunlight.
  • Valerian. Valerian has sedative qualities. This herb is listed on the FDA's list of generally safe products. However, its effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. Side effects include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm.
  • Kava. Kava is used for its calming effect for people with anxiety and depression. There have been reports of liver failure and death from this herb. Those at highest risk have existing impaired liver function. Other side effects include itchy, scaly skin, muscle weakness, and problems with coordination. Kava also interacts dangerously with certain medications, including alprazolam, an anti-anxiety drug. It increases the potency of certain drugs, including sleep medications, alcohol, and antidepressants.

Dietary Factors

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. In fact, a 2002 study found a correlation between high sugar consumption and higher rates of depression, although there is no evidence to suggest a causal association.

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. One study reported more depression in patients who had higher ratios of foods rich in omega 6 compared to those containing omega 3 fatty acids. (This imbalance has also been associated with heart disease.)

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

Caffeine. Studies have found an association between moderate consumption of caffeinated beverages and a lower incidence of suicide, indicating that coffee or tea might help reduce depression. One study supported the findings for a lower risk for suicide with moderate coffee intake but reported a higher risk for suicide with high coffee consumption. In such cases, coffee may not be the cause of the higher risk; women who drink such large amounts of coffee may be self medicating their depression. Heavy coffee use may also coincide with a higher risk for abuse of other substances, such as alcohol or cigarettes, which may increase the risk for suicide.

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

Exercise

Increasingly studies are reporting major benefits from exercise for people with depression. The following are some examples:

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, has been found to positively affect mood and may have clinical potential as a technique for improving and stabilizing mood. One study, in fact, suggested that men actually may have better results with yoga than with aerobic exercise. In the study men experienced significantly lower levels of tension, fatigue, and anger after yoga than after swimming. (Yoga and swimming tended to produce equal benefits in women.)


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

Social Support

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

References

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Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ, Viguera AC, et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA. 2006 Feb 1;295(5):499-507.

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Review Date: 12/21/2006
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
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