ANTIDEPRESSANT

any member of a class of drugs used in psychiatry to relieve depression. Such a drug commonly belongs to one of three chemical types: a tricyclic antidepressant (so called because its molecules are composed of three rings), a monoamine oxidase (MAO) inhibitor, or a serotonin reuptake inhibitor. Introduced in the late 1950s, antidepressant drugs have been used most widely in the management of major mental depression. Chemically speaking, depression is apparently caused by reduced quantities or reduced activity of the monoamine neurotransmitters serotonin and norepinephrine within the brain. All antidepressants achieve their effects by inhibiting the body's reabsorption or inactivation of these neurotransmitters, thus allowing them to accumulate and remain in contact longer with their receptors in nerve cells; these changes seem to be important in elevating mood and relieving depression. The tricyclic antidepressants act by inhibiting the inactivation of norepinephrine and serotonin within the brain. The tricyclics include imipramine, amitriptyline, desipramine, nortriptyline, and a number of other compounds. These drugs relieve symptoms in a high proportion (more than 70 percent) of depressed patients. As with the MAOs, the antidepressant action of tricyclic drugs may not become apparent until two to four weeks after treatment begins. The possible side effects include dry mouth, blurred vision, constipation, dizziness, and difficulty in urination. Cerebral and cardiac toxicity have been observed in some individuals. The monoamine oxidase inhibitorschiefly isocarboxazid, phenelzine, and tranylcyprominein general are used only after treatment with tricyclic drugs has proved unsatisfactory, because these drugs' side effects are unpredictable and their complex interactions are incompletely understood. The MAOs apparently achieve their effect by interfering with the action of monoamine oxidase, an enzyme that is involved with the breakdown of norepinephrine, serotonin, and dopamine within nerve cells. In the 1980s a new type of antidepressant called a serotonin reuptake inhibitor proved markedly successful. Called fluoxetine, it apparently achieves its therapeutic effect by interfering solely with the reabsorption of serotonin within the brain, thus allowing that neurotransmitter to accumulate there. Fluoxetine often relieves cases of depression that have failed to yield to tricyclics or MAOs, and it also produces fewer and less serious side effects than those drugs. It had thus become the single most widely used antidepressant by the end of the 20th century.