Antipsychotic drugs can ameliorate the types of delusions and hallucinations characteristic of bipolar disorder (see depression) and schizophrenia. The first drug of this type was reserpine, whose use dates from ancient Hindu medicine but whose reintroduction as an antipsychotic agent in 1954 marked the beginning of the large-scale use of antipsychotic drugs. Because of side effects, including depression, reserpine has been supplanted by phenothiazine drugs. The phenothiazine chlorpromazine (Thorazine) was the first to be widely applied to mental disorders and remains one of the standard drugs. Drugs of the phenothiazine family are most useful in the treatment of schizophrenia. They are thought to act in part by blocking dopamine receptors at the synapse, reducing brain activity. The phenothiazines and clozapine have been credited with a revolutionary transformation of mental health care, enabling increasing numbers of psychotic persons to function outside the hospital. Antipsychotic drugs may have negative side effects, such as the dulling of physical and mental functioning, tardive dyskinesia, and sedation.

Antianxiety drugs, including the propanediol meprobamate (Miltown or Equanil), and the more recent benzodiazephines—such as diazepam (Valium)—have found wide use in reducing tension and anxiety among individuals with less serious mental disorders, but may lead to addiction if abused. Although they form a chemically diverse group, the physiological effects of each are similar; in small doses they relieve anxiety by reducing muscular tension, and in larger doses they produce sedation, sleep, and anesthesia (see depressant). Antianxiety drugs are the most frequently prescribed pharmaceuticals in the United States.

Antidepressants appeared in the late 1950s, and have been used in the treatment of individuals suffering from major depression or the depression phase of bipolar disorder. Antidepressants include the tricyclics and monoamine oxidase (MAO) inhibitors. These drugs have the effect of increasing the concentration in the nervous system of catecholamines such as epinephrine. The toxic effects of the MAO inhibitors have been largely overcome in recent years, and the drugs are still used in many instances. They have been supplanted in many uses, however, by tricyclic compounds, such as amitriptyline (Elavil), and the newer serotonin increasers, such as fluoxetine (Prozac) and sertraline HCL (Zoloft). Tricyclics are chemically similar to phenothiazines, but that activate rather than tranquilize (see stimulant). The choice of an antidepressant often has more to do with its side effects than efficacy.

The element lithium, in the form lithium carbonate, has been widely used as an antimanic in cases of bipolar disorder (manic-depression), particularly to control manic episodes. Lithium alters the transport of sodium ions in nerve and muscle cells and affects the metabolism of catecholamines; the exact mechanism of action is unknown. The hallucinogenic drugs, such as mescaline and LSD, have been of research interest because they often mimic natural psychotic states.