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DEPRESSION

* Please note that most treatment modalities listed below are based on conventional medicine. PreventDisease.com does advocate the use of any pharmaceutical drug treatments. Long-term drug therapy is detrimental to human health. All drug information is for your reference only and readers are strongly encouraged to research healthier alternatives to any drug therapies listed.

WHAT IS DEPRESSION?

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, also called PMDD) and seasonal affective disorder (SAD).

(The other major mood disorder, not discussed in this report, is bipolar disorder, or manic-depressive illness, which is characterized by periods of depression alternating with episodes of excessive energy and activity. [ See 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 two weeks, and they must represent a change from previous behavior or mood. Depressed mood or loss of interest must be present.

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 should not follow or accompany manic episodes (such as in bipolar or other disorders).
They should 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. [For definition see below. ]

A long-term study conducted in 1997 found that episodes of major depression usually last about twenty weeks. Between 30% and 40% of depressed patients experience sudden attacks of anger that they describe as uncharacteristic and inappropriate.

Symptoms of depression in children may differ from those in adults. They may include:

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

Dysthymia (Chronic Depression)

Dysthymia, or chronic depression, afflicts 3% to 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 two 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 on 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 five years.

Atypical Depression

People with atypical depression generally overeat, oversleep, have a feeling of being weighed down, and have strong feelings of rejection.

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 and which may be replaced by a manic phase. Other 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 under eating and being sleepless.) SAD tends to last about five months in those who live in the northern part of America. It should be noted that 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. Nor does living in a Northern country with long winter nights guarantee a higher risk for depression.

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% to 8% of women in their reproductive years. A diagnosis of PDD depends on having five or more standard symptoms of major depression [ see above ] that occur during most menstrual cycles, with symptoms worsening a week or so before the menstrual period and resolving afterward.

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:

Grief normally has a limited duration. In people without any co-existing emotional disorder, bereavement usually lasts between three and six 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.

WHAT CAUSES DEPRESSION?

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, there is compelling evidence that it is a biologic phenomenon. Data from family, twin, adoption, and genetic studies have confirmed this. There is stronger risk of other family members getting depression with early recurrent forms of depression. 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.

Neurotransmitter Abnormalities

The basic biologic causes of depression are strongly linked to abnormalities in the delivery of certain key neurotransmitters (chemical messengers in the brain), most importantly the following:

Serotonin
Acetylcholine
Catecholamines, a group of neurotransmitters that consists of dopamine, norepinephrine, and epinephrine, also called adrenaline.

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, which has been linked to depression.

Hormonal Abnormalities

Reproductive Hormones. In women, the female hormones estrogen and progesterone most likely play a role in depression. [ See Box Specific Causes of Depression in Women.] Abnormal levels of certain stress and growth hormones may also play some role in depression.

Stress Hormones. Corticotropin-releasing factor (CRF), which is believed to be a stress hormone and a neurotransmitter, is also thought to be involved in depression. Increased CRF concentrations have been found in the cerebrospinal fluid of depressed patients. Other observations of CRF in depressed patients have supported this theory. CRF activity is also associated with sleep and appetite disruptions and with decreased libido.

Alterations in Brain Structure and Function

Patients with major depressive disorder have been found to have smaller hippocampi and amygdalas. (The hippocampus stores memory and activity in the amygdala has been correlated with activation of important emotional states, including anxiety and depression.) There is also evidence to suggest that the activity of certain pathways in the brain, responsible for regulating mood and associated behaviors and thoughts, is altered in depression.

A 2000 study supported previous evidence that in some older people with depression, atherosclerosis, or narrowing of the arteries in the brain, caused depression, rather than chemical or emotional factors.

Depression as Adaptive Strategy

Some experts theorize that low mood is an adaptive response to situations in which expectations fail to match achievements and active efforts produce no benefit (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 thoughtful time 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 cases could certainly occur in highly competitive societies that lack strong social support and where the media holds up unattainable images as desirable.) Such a theory does not, however, rule out biologic or other factors that can contribute to depressive disorders.

Specific Causes of 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.

Hormonal Changes

All women are at risk for emotional swings when they experience extreme hormonal shifts. The role of hormones in depression is not clear, but female hormones undoubtedly play some role in premenstrual dysphoria, postpartum depression, and SAD. These forms of depression recede or stop after menopause. Evidence for hormonal causes of depression is mostly based on observations of depression during specific stages in female development.

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 and 45) were most susceptible to depression, with 22% of this age group reporting symptoms of major depression. Premenstrual dysphoric disorder (severe depression before a period) specifically affects an estimated 3% to 8% of women in their reproductive years. [ See , Report # 79, Premenstrual Syndrome. ]

Postpartum Depression. Nearly every new mother experiences a short period of mild depression following childbirth (known as the "baby blues"). It is not considered postpartum depression, however, unless it persists beyond a week or two and is very severe. Studies have reported that between 8% and 20% of women have diagnosable postpartum depression within three months of delivery, with 5% in one study having suicidal thoughts. One study strongly suggested that the fluctuating levels of estrogen and progesterone accompanying childbirth may play a major role in postpartum depression, at least in women who are sensitive to such changes. Different studies have suggested that the following women may be at higher risk for postpartum depression are the following conditions:

A history of prior depressive episodes.
Being a new mother and having an infant with medical problems.
Psychological distress during or after the pregnancy.
Lacking social support or feeling as if it is lacking.
Having two or more children.

It should be noted that many male partners of new mothers also suffer from depression surrounding the birth of a child.

Depression During Pregnancy. A 2001 study found that depression during pregnancy was more common than depression after pregnancy, with the highest depression scores occurring in week 32. The authors commented that depression during pregnancy is a neglected area, and that the effects of depression on the fetus are largely unknown.

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.

Perimenopause. Depression often occurs around menopause (the perimenopausal period), when, in addition to hormonal changes, other factors (cultural pressures favoring young women, sudden recognition of aging, and sleeplessness) are involved. In one study, over half of perimenopausal women were diagnosed with major depression. (Women taking hormone replacement therapy during this period were just as likely to become depressed as those not on hormonal therapy, but the depression tended to be less severe.)

Postmenopause. One study suggests that average depression scores in women who were past menopause were 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.

Affiliate Behaviors and Oxytocin

A number of studies report that depression in women is more likely to be due to interpersonal problems, while in men depression tends to be attributed to stressful life events. One theory about the higher risk of depression in women concerns affiliate behaviors, which are those that involve activities surrounding relationships, and a peptide called oxytocin (OT).

Oxytocin, which is found in mammals, stimulates certain functions such as milk release during nursing and uterine contraction at labor. Under primitive conditions, the release of OT after puberty also coincided with early mating and breeding. Evidence suggests then that it may also play a role in affiliate behaviors such as maternal caregiving and sexual bonding after puberty. In certain cultures, however, there is a longer delay between puberty and marriage and childbirth. The release of OT, then, and the subsequent inability to mate may create feelings of loss and separation.

This theory is backed up by some research. Some studies suggest that young women most vulnerable to depression are those with risk factors that intensify feelings of separation. Such risk factors include the following:

Insecure attachments with parents
Shyness that limits interactions with others
Not having resources other than people to cope with separation.

This theory would also help explain why the rates of depression in men and women are fairly equal after menopause.

WHAT ARE THE RISK FACTORS FOR DEPRESSION?

Depression is second only to high blood pressure as a chronic condition encountered by primary care physicians. It is estimated that 10% of people who visit their physician suffer from major depression, although it in most cases it goes unrecognized or inadequately treated. Depression is an illness that can afflict anyone, regardless of age, race, class, or gender, and it is sometimes referred to as the common cold of mental illness. Although some evidence suggests the depression has increased over recent decades, one 40-year analysis found the overall rate to be holding steady, although the burden of depression may be shifting to women younger than 45.

Depression in Women

At any given time, five to nine percent of women are depressed, compared to two to three percent 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). [ See Box Specific Causes of 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 group to be depressed. One interesting report suggested 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. Studies of Amish and Orthodox Jewish communities, in which alcohol is not used, report an equal incidence of depression in men and women.

Depression in Children and the Elderly

Experts estimate that 2% of children and between 4% and 8% of teenagers suffer from depression. The highest incidence occurs in girls after puberty, although depression before puberty is more likely to occur in boys. Symptoms for depression in children may differ from those in adults and may be evident only from reports of problems in school. Studies suggest that when children or adolescents are treated, up to 80% will recover. Still, between 25% and 50% of such young people have a recurrence of depression within two years of the first episode.

Depression in the Elderly

Studies have suggested that, in general, a third of the elderly population is depressed. (According to one study, however, only 10% get treatment.) The aging process itself, however, is unlikely to be the cause in all cases. As with depression in young mothers, studies are not clear-cut:

An Italian study 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.)
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, nearly half were depressed, but as their function improved so did their mood.
Interestingly, one study suggested that the more pessimistic an elderly person is, the less likely he or she is to experience depression. Such individuals may be more able to accept the negative experiences that come with age than those with an optimistic personality.
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.

Social Status and Economic Considerations

Low Social and Economic Groups. Being in a low socioeconomic group is a major risk factor for depression. 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 hinge 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 living in California who immigrated to America had half the psychiatric illnesses as native-born Mexican-Americans regardless of their income. But, the longer the immigrants lived in the US, the greater their risk for psychiatric problems. Traditional Mexican cultural influences and social ties, then, 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.

Specific Social and Economic Risk Factors in Women. 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. The following are results of studies suggesting the difficulty of assessing the relationship between a woman's social status and depression, however.

In a report issued by the World Health Organization in 1996 on women worldwide, married women with children had a higher risk for depression than did married childless women, single women, or single or married men.
A survey of women in the Boston area reported, however, that women between the ages of 36 and 44 who had children were significantly less likely to be depressed than childless women. And the more children they had, the less depressed they tended to be. This study targeted older premenopausal women. The difference between this study and others may be due to the presence of older children, who might add a supportive emotional network, rather than dependent toddlers.
The perceived low status and isolation accompanying the role of housewife may play a role in a young mother's depression. A European study reported that depression increased in men and fell in women between 1980 and 1995, a period coinciding with more women entering the work force. (Work outside the home that fails to provide social support, however, will not necessarily help protect against depression.)
Other studies in the US have reported that grandmothers who care for their grandchildren and mothers of toddlers, regardless of whether they worked or not, have a very high risk for depression.

Consequences of Loss

Patients who have had serious bouts of depression usually cite a stressful life event as the precipitating factor for their illness. Recent loss of a loved one is the most frequently reported precipitant of acute depression, but all major (and even minor) losses cause grief. Losing a spouse through divorce or death is a major risk factor for depression in anyone anywhere. Traumatic events, such as abuse or even natural events such as earthquakes, can cause severe immediate or delayed depression from which recovery takes a long time. Most people are able to cope with the emotional pain and eventually move beyond it without becoming chronically depressed. People who develop acute or chronic depression after a loss may have predisposing factors, including genetic or biologic ones, that 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.

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; it may even be misdiagnosed as depression and go undetected.

Headaches. One study reported that nearly half of people with chronic tension headaches met criteria for either anxiety or depression. It wasn't clear whether the psychiatric disorder preceded or followed the onset of headaches. Two further studies found that people who had migraines were far more likely to be depressed (and vice versa) than those who did not have migraines. In fact, a 2000 study showed that 47% of migraine sufferers experienced depression. Some experts believe that a syndrome of migraine headaches, anxiety, and depression, which occurs in some people, is caused by common factors, such as abnormalities in certain 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

A 2001 study showed that smokers with a history of depression who stop smoking are seven times more likely to have another episode of depression than those who don't quit. This risk remains high for at least 6 months. 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 (Zyban, Wellbutrin), which is approved for helping people quit smoking, may be particularly useful in smokers who suffer from depression.

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 to relapses:

A person with borderline personality disorde r acts impulsively and has a poor self-image and unstable relationships. In one study, those with borderline personality disorder and major depression were more likely than those with either condition alone to plan and attempt suicide.
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 Disorders

Sleep abnormalities are an integral part of depressive disorders, with more than 90% of depressed patients experiencing insomnia. A study of male medical students found that young men who experience insomnia are twice as likely to suffer from depression at middle age. Genetic factors may play a role in the association between sleep disorders and depression. In one study of patients diagnosed with depression, family members with certain sleep abnormalities were found to be at greater risk for depression than those with normal sleep patterns. Abnormal sleep patterns often preceded the first episode of depression. Individuals with normal sleep patterns who were from families with abnormal sleep habits also appeared to have an increased risk for mood disorders.

Family History

A family history of mental illness, especially mood disorders, such as bipolar disorder, major depression, and chronic depression, appears to predispose a patient to the development of depression. Children of depressed parents are at high risk for depression and other emotional disorders.

Risk Factors for Seasonal Affective Disorder

Seasonal affective disorder (SAD) affects about one in 20 adults. About 80% of those who suffer from SAD are women. Obviously, people who live in the North are more apt to experience SAD than are Southerners.

HOW SERIOUS IS DEPRESSION?

General Outlook

Major 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 one 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 more severe, prolonged, or if there have been recurrences.

Dysthymic Disorder. In a study of dysthymic disorder, slightly more than half the patients recovered in a five-year period. In the same study, more than three-quarters suffered a major depressive episode. More than 90% recovered, but their risk for another episode was actually higher that patients who suffered just from major depression.

Risk for Suicide

Although an early study reported a risk of suicide in 15% of people with depression, a 2000 study gave strong evidence that the risk is much lower, between 2% to 9%, with the highest risk in patients who are hospitalized for depression. Some studies indicate that dysthymia may even pose a higher risk than episodic major depressive disorder. Some studies report the following for specific groups:

Gender. Depressed men are more likely to commit suicide than depressed women, although suicidal preoccupation or threats of suicide should always be treated seriously, especially in anyone known to be depressed.

Adolescents. In a 2001 study of adolescents, feeling connected with parents and family was protective for young people of both genders and all major ethnic groups. Risk factors included a previous suicide attempt, exposure to violence, either as victim or perpetrator, alcohol or drug use, and school problems. In one study, depression was the major factor in overdose among adolescents. (Impulsivity was the other major contributor to self-poisoning.) A parent should seek help as soon as possible for any child who exhibits signs of severe depression or when suicidal thoughts are expressed.

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.

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). 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.

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.

Heart Disease and Heart Attacks. Many studies have now reported strong associations between depression and an increase in the incidence and severity of heart attacks and death after a heart attack. Depression 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. The data are now suggesting that depression itself may be a true risk factor for heart disease as well as its increased severity. A number of studies have suggested that depression has biologic effects on the heart, including blood clotting and heart rate. A study in 2001, 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. Another 2001 study was the first to relate depression to risk of heart failure in people with hypertension. (On the other hand, studies also suggest that hardening of the arteries in the brain may cause depression, so depression may simply be a marker of severe or emerging heart disease.)

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 also appears to increase the risk for stroke in both women and men, particularly among African Americans. One study, for example, reported that young African American adults with depressive symptoms were at high risk for developing hypertension, an important cause of stroke (Young Caucasian adults with depression were at risk for hypertensive incidents but not hypertension itself.) Another study, published in 2001, confirmed that self-reported mood symptoms correlated with increased mortality 12 and 24 months after a stroke. Researchers speculate that depression and stroke might have common patterns of development.

Neurologic Decline. Depression in the elderly is associated with a decline in mental functioning, regardless of the presence of dementia. 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.

!Obesity!. One study reported that it was associated with childhood depression?

Increasing Sensations of Pain. Depression coincides with high pain scores in people with chronic diseases, such as rheumatoid arthritis.

Breast Cancer. A 2000 study found a link between prior depression and increased rates of breast cancer. Depression and breast cancer are each associated with estrogen levels, which may help explain the association. Other studies have found no link between breast cancer and emotional disorders.

Impact on Others

Effects on the Health of Offspring. One study has found that children of depressed parents are at greater risk for many medical conditions (eg, urinary and genital disorders, headaches, lung problems) and hospitalizations. But depressed children whose parents did not suffer from mood disorders were at no higher risk for medical disorders.

Increased Risk for Addictions. Severely depressed people are at high risk for alcoholism, smoking, and other forms of addiction. Pregnant women who drink may be increasing their child's risk for a future mental illness, as well as increasing their risk for delivering children with birth defects.

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.

Job Bias. In one British study, 60% of personnel directors said that they would never hire anyone for an executive position who had been previously diagnosed with depression. About a quarter of these professionals felt that formerly depressed people couldn't even handle clerical or manual jobs. (As a comparison, only 3% of personnel directors said that they thought diabetes would impair anyone's performance.) This strong bias against psychiatric disorders may be higher in England than in some other countries, but it is still indicative of the prejudices present in many cultures that inaccurately and unfairly separate psychiatric from physical conditions when assessing capability.

Substance Abuse

Alcohol and Drug Abuse. It is estimated that 25% of people with alcohol or drug abuse problems also have major depression. In one 2000 study, women with a history of depression were 2.6 times more likely to drink heavily than were women with no such history.

Smoking. Depression is a well-known risk factor for smoking and increases the danger of starting young. Indeed, nicotine may stimulate receptors in the brain that improve mood in certain people with genetically induced depression.

HOW IS DEPRESSION DIAGNOSED?

Relying on Family Physicians

Most people who are depressed do not seek psychiatric help and must rely on their family doctor. Unfortunately, there are a number of obstacles associated with this approach:

Studies suggest that although at least 10% of patients who visit a physician are suffering from major depression, most cases are unrecognized or inadequately treated. One study, in fact, reported that only 25% of family physicians accurately diagnose depression.
Patients themselves may be unable to sense or admit to their own depression. In one study, although 21% of patients who visited their family physicians were depressed, only one percent described their problem as depression.
To compound the problem, half the physicians in one study admitted to deliberately diagnosing a different problem, such as fatigue, anxiety, insomnia, or headache, in some of their patients who had depression. Reasons for doing this included uncertainty about the diagnosis, a concern that insurers wouldn't reimburse the patient for a diagnosis of depression, or because of the stigma attached to such a diagnosis.
Depression can be confused with other medical illnesses. Weight loss and fatigue, for example, accompany many conditions, some serious, but they can also occur with depression.
Many people lack insurance that will cover mental health costs. Such people are also likely to have adverse socioeconomic situations that increase their risk for depression.

Although not all patients who visit their physician should be screened for depression, certain individuals, such as the following, may be at higher risk and so 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 physician more frequently than expected.

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 consists 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. It is important to note, however, that these tests are limited, and mental health professionals generally diagnose depression based on symptoms and other criteria. [ For diagnostic criteria, see What Is Depression?.]

Diagnosing Depression in Specific Populations

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 may even be a predictor of Alzheimer's disease or an impending physical illness before the symptoms of the disease itself become evident.
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.

Diagnosing Depression in People from Nonwestern Cultures. People from nonwestern 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.

WHAT ARE THE GENERAL GUIDELINES FOR TREATMENT OF DEPRESSION?

Selecting the Optimal Therapeutic Choice

Patients with depression have a number of options, including psychotherapy, antidepressants, or both. The majority of people with acute depression respond to either the first or second trial of therapy. Still, more than two-thirds of people with depression, particularly the elderly, do not receive any therapy for it. Lack of health insurance is a major factor in these low treatment rates.

In general, the treatment choice depends on the degree and type of depression and other accompanying conditions.

Patients with Major Depression. Several approaches to patients with major depression are common:

A combination of antidepressants and structured psychotherapy is very effective for most patients with major depression. One study, for example, reported a response rate of 73% using cognitive behavioral therapy and Nefazodone, a newer antidepressant. Other studies also suggest that benefits persist when cognitive therapy is included in the treatment regimen. (In fact, 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 like vagus nerve stimulation and repetitive transcranial magnetic stimulation have also been found to be effective in some cases of treatment resistant depression.

Patients with Minor Depression. Patients with minor depression (fewer than five symptoms that persist for less than two years) may respond as well to watchful waiting and supportive care as to specific treatments, although this is unclear. 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 Dysthymia. Patients with dysthymia may respond to antidepressants.

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. Those with 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, 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 in order to provide protection from further deterioration or self-harm.

Mental Health Professionals. The only health professionals who can prescribe antidepressants are the following:

Psychiatrists. (These are mental health professionals with MDs.)
Any medical physician with an MD.
Some psychiatric 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 have a degree in psychiatry, psychology, or social work as well as several years of training at a psychoanalytic institute.
Psychologists have graduate-level training, including an internship in a mental healthcare facility.
A clinical social worker has a master's degree and two 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 areas by asking their doctor for a referral or contacting one of the mental health organizations. [See Where Else Can Help be Obtained for Depression, below.]
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 his or her health provider may be the most important component in recovery, as indicated by studies reporting that placebos relieve depression in about half of patients and in some cases actually work better than psychotherapy.
Patients should not be shy about considering a change in their therapist if they lack confidence in their current one.

General Treatment Guidelines for Specific Patient Groups

Pregnant and Nursing Women. Studies to date suggest that neither selective serotonin reuptake inhibitors (SSRIs) nor tricyclic antidepressants pose a higher than normal risk for birth defects or miscarriage when pregnant women take them. Studies on the effects on infants of nursing women taking SSRIs report very low levels of the medications in blood but no observable negative effects on the babies. Such continuing evidence suggesting that antidepressants are unlikely to be harmful during pregnancy and nursing is hopeful news for women with severe depression who are pregnant or wish to conceive. More research is needed, however, and most physicians advise women to avoid, if possible, any medications during pregnancy and nursing.

Children and Adolescents. Treatment choices for children and adolescents with depression varies according to severity:

Mild to Moderate Depression. Children and adolescents with mild to moderate depression should receive psychotherapy before medications are tried. One study suggested that there was very little difference in success rates among three major forms of psychotherapy: cognitive-behavioral therapy, family therapy, or supportive therapy. All achieved about an 80% recovery, with a 30% recurrent rate an average of 4 months after recovery. Severe depression and conflicts with parents made recovery more difficult.
Severe Depression. The American Academy of Child and Adolescent Psychiatry now recommends the SSRI antidepressants for children and adolescents with very severe depression that does not respond to psychotherapy. For best results, these drugs should be combined during the early acute phase with a mixture of psychotherapies, including cognitive-behavioral, interpersonal, and psychodynamic therapies. Initial drug treatments should continue for at least six months, and a maintenance phase should last another year or longer.

If medications are used, tricyclic antidepressants tend to be less useful in adolescents and children than they do in adults, and they have many side effects. MAOIs are also not commonly prescribed. Despite the fact that none of the SSRIs has been approved for use in children and adolescents, SSRIs are frequently prescribed in this age group. Fluoxetine is the most extensively studied SSRI in children. Some of the newer, designer antidepressants, such as nefazodone and venlafaxine, may also be safe and effective in children.

Elderly Adults. Ideally, elderly depressed patients should be treated with a combination of psychotherapy and antidepressants. Some experts recommend only psychotherapy or attention intervention for elderly patients with mild depression. In some older patients, a regular exercise program may even be sufficient to improve mood.

In many cases, however, psychotherapy is not available to elderly patients. Tricyclics are less expensive than SSRIs, but choosing between them may depend on specific conditions in older people:

Of possible significance for people with heart disease or stroke is a 2000 study reporting that the SSRI paroxetine (Paxil) may reduce the risk for blood clotting. (The other antidepressant in the study was a tricyclic antidepressant and had no such effect.) This suggests that the SSRIs may be the drugs of choice for treating patients with depression and a history of heart disease or stroke. The authors even suggest comparing SSRIs with aspirin for reducing blood clotting and for preventing heart disease or strokes in patients without depression. Tricyclic antidepressants, in any case, pose a higher risk than for adverse effects on the heart and possibly the lungs. (The older tricyclics e.g. amitriptyline (Elavil) and imipramine (Tofranil) have other severe side effects in older adults.)
SSRIs have fewer side effects than tricyclics.
It is commonly believed SSRIs pose a lower risk for falls than the older tricyclic antidepressants. Recent studies, however, have found no difference in risk between the two drug classes. (Whether all of the newer antidepressants pose a risk for falls is not yet known.)
Patients with Parkinson's may want to avoid SSRIs because they can increase the risk for tremor and other symptoms of the disease.

WHAT ARE THE DRUGS USED FOR DEPRESSION?

Drug Treatment Guidelines

Major Classes of Antidepressants. Antidepressants are very effective. One study reported that up to 90% of patients with major depression will improve with good compliance and adequate doses of the right antidepressant drug.

The primary target of most major antidepressant drug classes is the transport of the important neurotransmitters serotonin and norepinephrine. Such drug classes are the following:

Selective serotonin-reuptake inhibitors (SSRIs).
Tricyclic antidepressants (TCAs).
Monoamine oxidase inhibitors (MAOIs), including newer MAOIs called selective MAOIs.
A new group of drugs generally referred to as designer-antidepressants are similar to SSRIs, but have been developed to specifically target specific neurotransmitters (brain chemicals) other than, or in addition to, serotonin.
The herbal remedy St. John's Wort is included as a separate category, since it is unregulated and its chemical classification has not yet been determined.

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. Some examples of possible differences among drug classes include the following:

In one study, SSRIs, St. John's Wort, and moclobemide (a European selective MAOI) were better tolerated and had lower dropout rates than tricyclics.
SSRIs and some of the newer antidepressants may be beneficial in treating anxiety and certain subtypes of depressive disorders unresponsive to previous agents, including premenstrual dysphoric disorder and seasonal affective disorder, atypical depression, and recurrent brief depression.
MAOI inhibitors are the most effective antidepressants for atypical depression, but have some severe side effects and restrictive dietary rules.
According to one 2000 study, SSRIs may be more effective in women and tricyclics in men.

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 five to ten days.
Some experts recommend that the patients see their physician every one to two weeks until substantial improvement occurs. It is important to note, however, that it may take four to six weeks before a patient experiences the effects of any antidepressant.
Side effects usually diminish within one to four weeks. (Exceptions may be weight gain and sexual dysfunction.)
If no improvement occurs within three to four weeks, however, and the patient is not overly distressed by side effects, an alternative agent may be tried. More than 80% of patients respond to some antidepressant, although specific agents are helpful for only about half of patients. This suggests that if one medication fails, another has a good chance of being helpful. Newer agents with different mechanisms are being developed all the time that are improving response rates.
In general, patients should stay on antidepressants for at least six months after symptom relief to help prevent relapse. (Patients who improve within two 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 on-going antidepressants are the following:

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

Such patients, then, may need maintenance therapy for at least two years. Experts disagree, however, on the optimal length of maintenance therapy or the appropriate dosage. Once the patient and physician agree on withdrawal, it should be gradual, over two to three months, with monthly follow-ups.

It should be noted that 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. 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. According to one study, as many as 70% of elderly depressed patients did not adhere to antidepressant drug regimens. 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 nearly all 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 mirtazapine, bupropion, or nefazodone, may be effective alternatives. Sildenafil (Viagra), used for erectile dysfunction in men, may help reverse sexual dysfunction from antidepressants in both men and women. More research is in progress. One small study reported that the herbal remedy ginkgo biloba was associated with improved sexual function in patients taking antidepressants.
An increased risk of oral health problems caused by dry mouth is associated with long-term use of most antidepressants. The risks appear to be highest with some of the new designer antidepressants, with multiple drug use, and with the presence of oral infections. 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 serious. A few are mentioned in the individual drug discussions below, but many are not, and patients should inform the physician of any drugs they are taking, including over-the-counter-medications.
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 physician.

Warning Note:

An eight-year study has helped lay to rest very early reports of an association between Prozac and an increased risk for suicidal thoughts and behavior. In this study, there was actually an insignificant reduction in suicidal risk.

Paradoxically, there is some evidence to suggest that antidepressants might revitalize suicidal attempts in patients who were too despondent before treatment to make the effort. Experts warn that caregivers and physicians should be very vigilant for any signs of suicidal intent during the early acute phases of treatment. Patients themselves should be aware of any suicidal thoughts during initial recovery and seek help immediately.

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), fluvoxamine (Luvox), and citalopram (Celexa, Cipramil). Because they act on serotonin specifically, SSRIs have fewer side effects than the older antidepressants, which have more widespread effects in the body. Patients taking SSRIs report not only relief of depressive symptoms but also a higher level of efficiency, more energy, and better relationships with other people.

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, however, are also proving to be effective.
Other nondepressive disorders, including obsessive-compulsive disorder, panic disorder, and bulimia.
Impulsive and aggressive behaviors in psychiatric patients and in people with no mental health problems.
Depression and heart disease. There is some evidence that SSRIs may have benefits for the heart as well as the brain.
of Effectiveness and Use. SSRIs take, on average, two to four 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. Some patients may need to be on maintenance indefinitely. Studies to date have indicated that the standard SSRIs are probably safe, although it is unclear what the duration of treatment should be.

Drug Interactions. SSRIs interact with numerous drugs, and caution should be taken that the physician is well informed of any other medications the patient is taking. Of particular note is sibutramine (Meridia), which is used for weight loss, and which also affects serotonin levels.

Side Effects of SSRIs. Side effects include the following:

Nausea and gastrointestinal problems. These effects usually wear off over time.
Agitation, insomnia, mild tremor, and impulsivity occur in 10% and 20% of people who take SSRIs, these symptoms may be particularly problematic in patients who also suffer from anxiety, sleeplessness, or both. Such side effects may persist. On the other hand, about 20% of SSRI-treated patients experience drowsiness, which may be counteracted by taking the medication at bedtime.
Dry mouth is common and can increase the risk for cavities and mouth sores.
Lack of motivation, fatigue, and mental dullness.
Headache.
Weight Gain. Some weight loss during the first few weeks of treatment may occur, but over time patients on maintenance treatment typically return to their pretreatment weight or gain weight. 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 dysfunction, including delayed or loss of orgasm and low sexual drive, is now a well-known side effect of SSRIs. It should be noted however that in one 2001 study, sexual desire increased in 20% of women and 27% of men taking the SSRI. In patients with normal sexual function, only about 15% of patients experienced greater sexual dysfunction, which was generally mild to moderate and mostly took the form of less sexual interest. Taking a supervised drug "holiday" on the weekend may improve sexual function during that time. (Withdrawal symptoms may develop and include return of depression, sleep problems, exhaustion, and dizziness. Prozac, with its longer duration of action, appears to be associated with a lower risk for withdrawal symptoms than shorter-lasting SSRIs, but a weekend off this drug may not be long enough to restore sexual function.) The physician may recommend other strategies to circumvent sexual dysfunction, including reducing the antidepressant dosage, switching antidepressants, or adding medication to curtail the side effect. Some of the newer, so-called designer antidepressants may have less severe impairment of sexual function.
There have been some reports of worsened glaucoma in patients taking SSRIs. This is a very rare complication and it isn't clear that there is a causal relationship. Patients with glaucoma who take SSRIs should have their eyes examined regularly.
Withdrawal symptoms. Dizziness, muscle weakness or pain, odd sensations in the limbs, nausea, loose stools, visual disturbances, irritability, insomnia, mood worsening, and headaches 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.

Management of SSRI-Induced Side Effects

Elderly people taking these drugs should take the lowest dose possible, and those with heart problems should be monitored closely. Over the years, some patients taking SSRIs have reported a group of side effects, known as extrapyramidal symptoms, which are similar to those in Parkinson's disease and affect the nerves and muscles controlling movement and coordination. They are uncommon, and when they develop they tend to occur within the first month of treatment.
High doses or interactions with other drugs may cause hallucinations, confusion, changes in blood pressure, stiffness, and irregular heart beats. Serious interactions can occur with other antidepressants, such as tricyclics and, of particular note, MAOIs [see below]. 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.
Death from overdose is extremely rare.

Designer Antidepressants

A number of drugs have now been developed that target other neurotransmitters, such as norepinephrine, alone or in addition to serotonin. In general, the advantages of the new designer antidepressants are as follows:

They may be more tolerable 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 on sexual function than SSRIs, and some people have even reported enhanced sexuality with some of them.
They may be more effective for severely depressed patients than the SSRIs.
Some, such as mirtazapine and nefazodone, may also provide relief from insomnia and anxiety, that are common in many depressed patients. (SSRIs and antidepressants that increase uptake of both serotonin and norepinephrine generally pose a higher risk for insomnia.)

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

Bupropion. Bupropion (Wellbutrin, Zyban) is particularly effective for a number of conditions and is also used for smoking cessation. It causes less sexual dysfunction than SSRIs. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures; this side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Venlafaxine. Venlafaxine (Effexo