Major depressive disorder (also known as clinical depression, major depression, unipolar depression, or unipolar disorder) is a mental disorder typically characterized by a pervasive low mood, low self-esteem, and loss of interest or pleasure in usual activities. The term was selected by the American Psychiatric Association for the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) classification for the symptom cluster, and has become widely used since. The general term depression is often used to describe the disorder, but since it is also used to describe temporary sadness or a depressed mood, more precise terminology is preferred in clinical use and research. Major depression is an often disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States around 3.4% of people with major depression commit suicide, and up to 60% of all people who commit suicide have depression or another mood disorder.

The diagnosis of major depressive disorder is based on the patient's self-reported experiences, behavior reported by relatives or friends, and mental state. There is no laboratory test for major depression, although physicians generally request tests for physical conditions that may cause similar symptoms. The most common time of onset is between the ages of 30 and 40 years, with a later peak between 50 and 60 years. Major depression occurs about twice as frequently in women as in men, although men are at higher risk for suicide.

Most patients are treated in the community with antidepressant medication and supportive counseling, and some with psychotherapy. Admission to hospital may be necessary in cases associated with self-neglect or a significant risk of harm to self or others. A minority with severe illness may be treated with electroconvulsive therapy (ECT), under a short-acting general anaesthetic. The course of the disorder varies widely, from a once-only occurrence lasting months to a lifelong disorder with recurrent major depressive episodes. Depressed individuals have a shorter life expectancy than those without depression, being more susceptible to medical conditions such as heart disease. Sufferers and former patients may be stigmatized.

The understanding of the nature and causes of depression has evolved over the centuries; nevertheless, many aspects of depression are still not fully understood, and are the subject of debate and research. Psychological, psycho-social, evolutionary and biological causes have been proposed. Psychological treatments are based on theories about personality, interpersonal communication, and unduly negative thoughts. The monoamine chemicals serotonin, norepinephrine, and dopamine are naturally present in the brain and assist communication between nerve cells. Monoamines have been implicated in depression, and most antidepressants work to increase the active levels of at least one.

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