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The Merck Manual of Medical Information--Home Edition
Section 7. Mental Health Disorders
Chapter 84

Depression and Mania

Depression and mania represent the two major poles of mood disorders. Mood disorders are psychiatric illnesses in which emotional disturbances consist of prolonged periods of excessive depression or elation (mania). Mood disorders are also called affective disorders. Affect (emphasis on the first syllable) means emotional state as revealed through facial expressions and gestures.

Sadness and joy are part of the normal experience of everyday life and are different from the severe depression and mania that characterize mood disorders. Sadness is a natural response to loss, defeat, disappointment, trauma, or catastrophe. Sadness may be psychologically beneficial because it permits a person to withdraw from offensive or unpleasant situations, which may aid recovery.

Grief or bereavement is the most common of the normal reactions to a loss or separation, such as the death of a loved one, divorce, or romantic disappointment. Bereavement and loss don't generally cause persistent, incapacitating depression except in people predisposed to mood disorders.

Success and achievement normally incite feelings of elation. However, elation can sometimes be a defense against depression or a denial of the pain of loss. People who are dying sometimes have brief periods of elation and restless activity, and some recently bereaved people may even become elated rather than grieve normally. In people predisposed to mood disorders, these reactions may be the prelude to mania.

Although 25 to 30 percent of all people will experience some form of excessive mood disturbance during their life, only about 10 percent will have a disorder severe enough to require medical attention. Of these, a third have long-lasting (chronic) depression, and most of the remainder have recurring episodes of depression. Chronic and recurring depressions are termed unipolar. Nearly 2 percent of the population have a condition called manic-depressive illness or bipolar disorder, in which periods of depression alternate with periods of mania (or with periods of less severe mania known as hypomania).


Depression is a feeling of intense sadness; it may follow a recent loss or other sad event but is out of proportion to that event and persists beyond an appropriate length of time.

After anxiety, depression is the most common psychiatric disorder. An estimated 10 percent of the people who see their doctors for what they think is a physical problem are actually experiencing depression. Depression typically begins in the 20s, 30s, or 40s. People born in the latter part of the 20th century seem to have higher rates of depression than those of previous generations, in part because of higher rates of substance abuse.

An episode of depression typically lasts for 6 to 9 months, but in 15 to 20 percent of the people, it lasts for 2 years or more. Episodes generally tend to recur several times over a lifetime.


The causes of depression aren't fully understood. A number of factors may make a person more likely to experience depression, such as a family tendency (heredity), side effects of certain medications, an introverted personality, and emotionally upsetting events, particularly those involving a loss. Depression may also arise or worsen without any apparent or significant life stress.

Women are twice as likely as men to experience depression, though the reasons aren't entirely clear. Psychologic studies show that women tend to respond to adversity by withdrawing into themselves and blaming themselves. In contrast, men tend to deny adversity and throw themselves into activities. Of biologic factors, hormones are the ones most involved. Changes in hormone levels, which can create mood changes shortly before menstruation (premenstrual tension) and after childbirth (postpartum depression), might play some role in women. Similar hormonal changes may occur with the use of oral contraceptives in women who have experienced depression. Abnormal thyroid function, which is fairly common in women, may also be a factor.

Depression that follows a traumatic event, such as the death of a loved one, is called situational depression. Some people become temporarily depressed in reaction to certain holidays (holiday blues) or meaningful anniversaries, such as the anniversary of a loved one's death. Depression without an apparent precipitating event is called endogenous depression. These distinctions, however, aren't very important, since the effects and treatment of the depression are similar.

Depression may also occur with, or be caused by, a number of physical diseases or disorders. Physical disorders may cause a depression directly (such as when thyroid disease affects hormone levels, which can induce depression) or indirectly (such as when rheumatoid arthritis causes pain and disability, which can lead to depression). Often, depression that results from a physical disorder has both direct and indirect causes. For example, AIDS may cause depression directly if the human immunodeficiency virus (HIV), which causes AIDS, damages the brain; AIDS may cause depression indirectly by having an overall negative impact on the person's life.

Various prescription drugs, most notably drugs used to treat high blood pressure, can cause depression. For unknown reasons, corticosteroids often cause depression when they are produced in large amounts as part of a disease, as in Cushing's syndrome, but they tend to cause elation when they are given as medication.

A number of psychiatric conditions can predispose a person to depression, including certain anxiety disorders, alcoholism and other substance abuse disorders, schizophrenia, and the early phase of dementia. (see box Physical Disorders That Can Cause Depression in this chapter)


Symptoms typically develop gradually over days or weeks. A person entering a depression may appear slow and sad or irritable and anxious. A person who tends to withdraw, speak little, stop eating, and sleep little is experiencing what is called a vegetative depression. A person who, in addition, is very restless--wringing the hands and talking continuously--is experiencing what is called an agitated depression.

Many people with depression can't experience emotions--including grief, joy, and pleasure--normally; in the extreme, the world appears to have become colorless, lifeless, and dead. Thinking, speech, and general activity may slow down so much that all voluntary activities stop. Depressed people may be preoccupied with intense feelings of guilt and self-denigrating ideas and may not be able to concentrate well. They are often indecisive and withdrawn, feel progressively helpless and hopeless, and think about death and suicide.

Most depressed people have difficulty falling asleep and awaken repeatedly, particularly early in the morning. A loss of sexual desire or pleasure in general is common. Poor appetite and weight loss sometimes lead to emaciation, and in women menstrual periods may stop. However, overeating and weight gain are common in milder depressions.

In about 20 percent of depressed people, the symptoms are milder but the illness lasts years, often decades. This dysthymic variant of depression often begins early in life and is associated with distinct changes in personality. People with this condition are gloomy, pessimistic, humorless, or incapable of having fun; passive and lethargic; introverted; skeptical, hypercritical, or constantly complaining; and self-critical and full of self-reproach. They are preoccupied with inadequacy, failure, and negative events, sometimes to the point of morbid enjoyment of their own failures.

Some depressed people complain of having a physical illness, with various aches and pains or fears of calamity or of becoming insane. Others think they have illnesses they believe to be incurable or shameful, such as cancer or sexually transmitted diseases, and that they are infecting other people.

About 15 percent of depressed people, most commonly those with severe depression, have delusions (false beliefs) or hallucinations, seeing or hearing things that aren't there. They may believe that they have committed unpardonable sins or crimes or may hear voices accusing them of various misdeeds or condemning them to death. In rare cases, they may imagine that they see coffins or deceased relatives. Feelings of insecurity and worthlessness may lead severely depressed people to believe that they are being watched and persecuted. These depressions with delusions are termed psychotic depressions.

Thoughts of death are among the most serious symptoms of depression. Many depressed people want to die or feel they are so worthless that they should die. As many as 15 percent of people with severe depression exhibit suicidal behavior. A suicide plan represents an emergency situation, and someone with such a plan should be hospitalized and kept under supervision until treatment reduces the risk of suicide. (see page 411 in Chapter 85, Suicidal Behavior)


A doctor is usually able to diagnose depression from its signs and symptoms. A previous history of depression or a family history of depression helps to confirm the diagnosis.

Sometimes standardized questionnaires are used to help measure the degree of depression. Two such questionnaires are the Hamilton Depression Rating Scale, conducted verbally by an interviewer, and the Beck Depression Inventory, a self-administered questionnaire.

Laboratory tests, usually blood tests, may help a doctor determine the cause of some depressions. This is particularly useful for women, in whom hormonal factors could contribute to depression.

In cases that are difficult to diagnose, doctors may perform other tests to confirm the diagnosis of depression. For example, because sleep problems are such a prominent sign of depression, doctors who specialize in diagnosing and treating mood disorders may use a sleep electroencephalogram to measure the time it takes for rapid eye movement sleep (the period during which dreaming occurs) to begin after the person falls asleep. (see page 301 in Chapter 64, Sleep Disorders) Normally, it takes about 90 minutes. In a person with depression, it usually takes less than 70 minutes.

Prognosis and Treatment

An untreated depression may last 6 months or longer. Although mild symptoms persist in many people, functioning tends to return to normal. Nonetheless, most people with depression experience repeated episodes of depression, an average of four to five times over a lifetime.

Depression today is usually treated without hospitalization. However, sometimes a person should be hospitalized, especially if he is seriously contemplating suicide or has attempted it, is too frail because of weight loss, or is at risk for heart problems because of severe agitation.

Medications are the cornerstone of treatment for depression today. Other treatments include psychotherapy and electroconvulsive therapy. Sometimes a combination of these different therapies is used.

Drug Treatment

Several types of drugs--tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, and psychostimulants--are available, but they must be taken regularly for at least several weeks before they begin to work. The chances that any given antidepressant will work for a particular person are about 65 percent.

The adverse effects vary with each type of drug. The tricyclic antidepressants often cause sedation and lead to weight gain. They can also be associated with an increased heart rate, a decrease in blood pressure when the person stands, blurred vision, dry mouth, confusion, constipation, difficulty in starting to urinate, and delayed orgasm. These effects are called anticholinergic effects and are often more pronounced in the elderly. (see box, page 41)

Antidepressants that are similar to the tricyclic antidepressants have other adverse effects. Venlafaxine may slightly raise the blood pressure. Trazodone has been associated with painful erection (priapism). Maprotiline and bupropion taken in quickly escalating doses can induce seizures. However, bupropion doesn't cause sedation, doesn't affect sexual function, and is often useful in patients with depression and slowed thinking.

Types of Antidepressants

Tricyclic and similar antidepressants



Selective serotonin reuptake inhibitors


Monoamine oxidase inhibitors




The selective serotonin reuptake inhibitors (SSRIs) represent a major improvement in the treatment of depression in that they tend to cause fewer adverse effects than the tricyclic antidepressants. Also they are generally quite safe in people who have depression and a coexisting physical disorder. Although they can cause nausea, diarrhea, and headache, these adverse effects are either mild or go away with continued use. For these reasons, doctors often select SSRIs first when treating depression. SSRIs are particularly useful in the treatment of dysthymia, which requires long-term drug therapy. Moreover, SSRIs are quite effective in obsessive-compulsive disorder, panic disorder, social phobia, and bulimia (an eating disorder), which often coexist with depression. The main disadvantage of SSRIs is that they commonly cause sexual dysfunction.

Monoamine oxidase inhibitors (MAOIs) represent another class of antidepressant drug. However, people who use MAOIs must adhere to a number of dietary restrictions and follow special precautions. For example, they should not eat foods or beverages that contain tyramine, such as beer on tap, red wines (including sherry), liqueurs, overripe foods, salami, aged cheeses, fava or broad beans, yeast extracts (marmite), and soy sauce. They must avoid drugs such as phenylpropanolamine and dextromethorphan, found in many over-the-counter cough and cold remedies, which cause the release of adrenaline and can cause a sudden and severe rise in blood pressure. Certain other drugs should also be avoided by people who take MAOIs, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, and meperidine (a painkiller).

People taking MAOIs usually are instructed to carry an antidote, such as chlorpromazine or nifedipine, at all times. If a severe, throbbing headache occurs, they should take the antidote at once and go to the nearest emergency room. Because of the difficult dietary restrictions and necessary precautions, MAOIs are rarely prescribed except for depressed people who haven't improved with other antidepressants.

Psychostimulants, such as methylphenidate, are generally reserved for depressed people who are withdrawn, slowed, and fatigued or who haven't improved after using all other classes of antidepressants. Their abuse potential is high. Because psychostimulants tend to work quickly (within a day) and facilitate ambulation, they are sometimes prescribed for elderly depressed people who are convalescing from surgery or a protracted illness.


Psychotherapy used with antidepressants can greatly enhance the results of medication. (see page 389 in Chapter 80, Overview of Mental Health Care) Individual or group psychotherapy can help the person gradually resume former responsibilities and adapt to the normal pressures of life, building on the improvement made by drug treatment. With interpersonal psychotherapy, the person receives supportive guidance for adjusting to changes in life roles. Cognitive therapy can help change a person's hopeless and negative thinking. Psychotherapy alone may be just as effective as drug therapy for milder depressions.

Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is used to treat severe depression, particularly when the person is psychotic, is threatening to commit suicide, or is refusing to eat. This type of therapy is usually very effective and can relieve depression quickly, unlike most antidepressants, which can take up to several weeks. The speed with which electroconvulsive therapy takes effect can save lives.

With electroconvulsive therapy, electrodes are placed on the head and an electric current is applied to induce a seizure in the brain. For reasons that aren't understood, the seizure alleviates depression. Usually five to seven treatments, one treatment every other day, are given. Because the electric current can cause muscle contractions and pain, the person receives general anesthesia during treatments. Electroconvulsive therapy may cause some temporary (rarely permanent) loss of memory.


Mania is characterized by excessive physical activity and feelings of extreme elation that are grossly out of proportion to any positive event. Hypomania is a milder form of mania.

Although a person can have depression without manic episodes (unipolar disorder), mania most commonly occurs as a part of manic-depressive illness (bipolar disorder). (see page 409 in this chapter) The few people who appear to experience only mania may actually have mild or brief depressive episodes. Mania and hypomania are less common than depression, and they are also less easily recognized--while extreme and protracted sadness may prompt a visit to a doctor, elation much less commonly does (because people with mania are unaware that anything is wrong with their mental state or behavior). A doctor must rule out an underlying physical disease in a person who is experiencing mania for the first time, without a previous depressive episode.

Physical Disorders That Can Cause Mania

Side effects of drugs

Antidepressants (most)


Syphilis (late stage)


Hormonal disorders

High levels of thyroid hormone

Connective tissue disease

Systemic lupus erythematosus

Neurologic disorders

Brain tumors
Head injury
Huntington's chorea
Multiple sclerosis
Sydenham's chorea
Temporal lobe epilepsy

Symptoms and Diagnosis

Manic symptoms typically develop rapidly over a few days. In the early (milder) stages of mania, the person feels better than normal and often appears brighter, younger, and more energetic.

A person who is manic is generally elated but may also be irritable, cantankerous, or frankly hostile. He typically believes he is quite well. A lack of insight into his condition, along with a huge capacity for activity, can make the person impatient, intrusive, meddlesome, and aggressively irritable when crossed. Mental activity speeds up (a condition called flight of ideas). The person is easily distracted and constantly shifts from one theme or endeavor to another. The person may have false convictions of personal wealth, power, inventiveness, and genius and may temporarily assume a grandiose identity, sometimes believing that he is God.

The person may believe he is being assisted or persecuted by others or have hallucinations, hearing and seeing things that aren't there. The need for sleep decreases. A manic person is inexhaustibly, excessively, and impulsively involved in various activities (such as risky business endeavors, gambling, or perilous sexual behavior) without recognizing the inherent social dangers. In extreme cases, mental and physical activity is so frenzied that any clear link between mood and behavior is lost in a kind of senseless agitation (delirious mania). Immediate treatment is then required, because the person may die of sheer physical exhaustion. In less severely overactive mania, hospitalization may be needed to protect the person and his family from ruinous financial or sexual behavior.

Mania is diagnosed by its symptoms, which are typically obvious to the observer. However, because people with mania are notorious for denying that there is anything wrong with them, doctors usually have to obtain information from family members. Questionnaires aren't used as widely as in depression.

Symptoms of Mania


  • Elation, irritability, or hostility
  • Momentary tearfulness

Other psychologic symptoms

  • Inflated self-esteem, boasting, grandiose behavior
  • Racing thoughts, new thoughts triggered by word sounds rather than meaning, tendency to be distracted easily
  • Heightened interest in new activities, increased involvement with people (who are often alienated because of the person's intrusive and meddlesome behavior), buying sprees, sexual indiscretions, foolish business investments

Psychotic symptoms

  • Delusions of exceptional talent
  • Delusions of exceptional physical fitness
  • Delusions of wealth, aristocratic ancestry, or other grandiose identity
  • Having visions or hearing voices (hallucinations)
  • Paranoia

Physical symptoms

  • Increased activity level
  • Possible weight loss from increased activity and inattention to diet
  • Decreased need for sleep
  • Increased sexual desire


Untreated episodes of mania end more abruptly than those of depression and are typically shorter, lasting from a few weeks to several months. Because mania is a medical and social emergency, a doctor makes all attempts to treat the patient in a hospital.

A drug called lithium can reduce the symptoms of mania. Because lithium takes 4 to 10 days to work, a drug that works rapidly, such as haloperidol, is often given at the same time to control excited thought and activity. However, haloperidol can cause muscle stiffness and unusual movements. Therefore, haloperidol is given in small doses, in combination with a benzodiazepine, such as lorazepam or clonazepam, which enhances haloperidol's antimanic effects while reducing its unpleasant side effects.

Manic-Depressive Illness

Manic-depressive illness, also called bipolar disorder, is a condition in which periods of depression alternate with periods of mania or lesser degrees of excitement.

Manic-depressive illness affects slightly less than 2 percent of the population to some degree. The illness is believed to be hereditary, although the exact genetic defect is still unknown. Manic-depressive illness is equally common in men and women and typically begins in the teens, 20s, or 30s.

Symptoms and Diagnosis

Manic-depressive illness usually begins with depression and includes at least one period of mania at some time during the illness. Episodes of depression typically last 3 to 6 months. In the most severe form of the illness, called bipolar I disorder, depression alternates with intense mania. In the less severe form, called bipolar II disorder, short depressive episodes alternate with hypomania. Symptoms of bipolar II disorder often recur in certain seasons, for example, depression occurs in the fall and winter, and brief excitement occurs in the spring or summer.

In an even milder form of manic-depressive illness, called cyclothymic disorder, periods of elation and depression are less severe, typically last for only a few days, and recur fairly often at irregular intervals. Although cyclothymic disorder may ultimately evolve into manic-depressive illness, in many people cyclothymic disorder never leads to major depression or mania. Having a cyclothymic disorder may contribute to a person's success in business, leadership, achievement, and artistic creativity. However, it may also cause uneven work and school records, frequent change of residence, repeated romantic breakups or marital failure, and alcohol and drug abuse. In about a third of people with cyclothymic disorder, these symptoms can lead to a mood disorder that requires treatment.

The diagnosis of manic-depressive illness is based on the distinctive pattern of symptoms. A doctor determines whether the person is experiencing a manic or depressive episode so that the correct treatment can be given. About one in three people with bipolar disorder experience manic (or hypomanic) and depressive symptoms simultaneously. This condition is known as a mixed bipolar state.

Prognosis and Treatment

Manic-depressive illness recurs in nearly all cases. Episodes may sometimes switch from depression to mania, or vice versa, without any period of normal mood in between. Some people cycle more rapidly through episodes than others. Up to 15 percent of the people with manic-depressive illness, mostly women, have four or more episodes a year. People who cycle rapidly are more difficult to treat.

Manic or hypomanic episodes in manic-depressive illness can be treated like acute mania. Depressive episodes are treated like depression. However, most antidepressants can cause swings from depression to hypomania or mania and sometimes cause rapid cycling between them. Therefore, these drugs are used for only short periods, and their effect on mood is closely monitored. At the first sign of a swing to hypomania or mania, the antidepressant is stopped. Antidepressants least likely to cause mood switching are bupropion and the monoamine oxidase inhibitors. Optimally, most people with manic-depressive disorder should be given mood-stabilizing drugs, such as lithium or an anticonvulsant.

Lithium has no effect on normal mood but reduces the tendency toward mood swings in about 70 percent of the people with manic-depressive illness. A doctor monitors the level of lithium in the blood with blood tests. Possible adverse effects of lithium include tremor, muscle twitching, nausea, vomiting, diarrhea, thirst, excessive urination, and weight gain. Lithium can make acne or psoriasis worse, can cause the blood levels of thyroid hormone to fall, and rarely can cause excessive urination. A very high level of lithium in the blood can cause a persistent headache, mental confusion, drowsiness, seizures, and abnormal heart rhythms. Adverse effects are more likely to occur in the elderly. Women who are trying to become pregnant must stop taking lithium, because lithium can (rarely) cause heart defects in a developing fetus.

Newer drug treatments have evolved over the past several years. These include the anticonvulsants carbamazepine and divalproex. However, carbamazepine can seriously reduce the number of red and white blood cells, and divalproex can cause liver damage (primarily in children). With careful monitoring by a doctor, these problems are rare, and carbamazepine and divalproex are useful alternatives to lithium, especially for people with the mixed or rapid cycling form of manic-depressive illness who haven't responded to other treatments.

Psychotherapy is often recommended for those taking mood stabilizing drugs, mostly to help them stay with the therapy. Some people taking lithium feel less alert, less creative, and less in control than normal. However, an actual decrease in creativity is uncommon, particularly since lithium allows people with manic-depressive illness to lead a steadier life, improving their overall work performance. Group therapy is often useful for helping people and their spouses or relatives understand the illness and better cope with it.

Phototherapy is sometimes used to treat people with manic-depressive illness, especially those who have milder and more seasonal depression: autumn-winter depression and spring-summer hypomania. With phototherapy, the person is placed in a closed room that is bathed in artificial light. The light is controlled to mimic the season that the therapist is trying to create: longer days for summer and shorter days for winter. If the dose of light is excessive, the person may switch to hypomania or, in some cases, eye damage can occur. Therefore, phototherapy should be supervised by a doctor who specializes in the treatment of mood disorders.

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