Antipsychotic Drugs

Antipsychotics are medications that target psychotic symptoms such as delusions and hallucinations. These medications, also known as neuroleptics or major tranquilizers, are also commonly used as mood stabilizers and for nonspecific sedation. The array of antipsychotics is expanding, as new agents are developed with wider applications than those of the older medications. Many substances can produce psychosis, which is often treated with antipsychotic drugs. With one notable exception, antipsychotic drugs have little abuse potential.

Psychosis is defined by Stedman's Medical Dictionary as "a mental and behavioral disorder causing gross distortion or disorganization of a person's mental capacity, affective response, and capacity to recognize reality, communicate, and relate to others." All antipsychotics treat psychosis by blocking postsynaptic dopamine (D2) receptors in the brain. Antipsychotic efficacy appears to occur in a window of 60% to 80% D2 receptors blockade. Antagonism below 60% confers less antipsychotic effect, whereas blockade of more than 80% of the receptors produces extrapyramidal symptoms.

There are two categories of antipsychotics, typical and atypical, which differ by their receptor activities. These categories are also known as first generation and second generation antipsychotics. In addition to D2 blockade, atypical antipsychotics are active at serotonin receptors (5-HT2) and other dopamine receptor subtypes. Atypical agents are thought to bind less tightly to D2 receptors and occupy these receptors more intermittently than do typical antipsychotics. These variations explain the differences in therapeutic effects and side effects, which may be more benign in the atypical drugs. Other important distinguishing factors between these two classes include cost and Food and Drug Administration (FDA)-approved indications. The atypical agents are newer and much more expensive than the typical agents. The atypical agents have FDA indications as mood stabilizers and are used to treat acute mania and depression and to provide maintenance in bipolar disorder.