Melancholia, a severe disturbance of mood, movement, and thought, has been recognized for millennia. It is a brain disease with abnormalities in neurochemical, neurohormonal, metabolic, and electrophysiologic processes.

The syndrome is considered moderately heritable. Under circumstances of stress at critical phases of development, the genetic predisposition is expressed, and the mood disorder develops. A prominent feature of melancholia is an “abnormal stress response state.” Recognizing melancholia is a clinical judgment that combines a signature psychopathology with identifiable hormonal and neurophysiologic perturbations.

Melancholia is well defined in the literature of medicine. Its characteristic psychopathology and laboratory testing are established in evidence, if not yet by consensus. Guidelines for the examination of melancholic patients and the differential diagnosis of depressive syndromes derive from the clinical experience and investigations of many authors. Suicide is a special risk for sufferers of melancholia, and prevention strategies are established.

Two effective treatment modalities for melancholic patients have been developed. Convulsive therapy is the oldest and the most effective intervention; guidelines for its effective application are well known. Medications are also delineated from the evidence, but the therapeutics has been distorted by the pharmaceutical industry. An objective consensus is needed. The efficacy of psychotherapies and other proposed treatment interventions has yet to be substantiated.