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Prior to the 1950s, pharmacologic therapy for schizophrenia primarily involved the administration of sedatives-hypnotics, such as barbiturates, to calm patients during their periods of acute agitation. The discovery of chlorpromazine and haloperidol enabled treatment specifically aimed at the underlying physiologic disturbance. Although these drugs were effective against the positive signs of psychosis (e.g., delusions, hallucinations, disorganized thought), they provided no treatment for the negative signs (e.g., avolition, alogia, social withdrawal). Furthermore, these drugs were associated with significant adverse effects.

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In the 1990s, the second generation of therapeutic drugs, or atypical antipsychotics, were released for use. These drugs are characterized by minimal extrapyramidal side effects when taken at effective dosages and activity against the negative signs of schizophrenia. In 2002, aripiprazole, termed a third-generation antipsychotic, was released for use in the treatment of schizophrenia (Table 174-1).

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Table 174-1 Common Antipsychotics
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These drugs were originally referred to as major tranquilizers, because of their ability to calm patients. Because they are not simply sedatives, this term is inappropriate. These drugs were also termed neuroleptics, which refers to their ability to slow movement. With the advent of the atypical antipsychotics, it became clear that antipsychotic properties do not necessarily parallel neuroleptic properties. For this reason, the preferred term is antipsychotics. Although antipsychotic is a useful term, these drugs are sometimes administered to treat other conditions, such as agitation, nausea and emesis, various headache conditions; to suppress hiccups; and to control various involuntary motor disorders, such as Tourette syndrome, Huntington chorea, and basal ganglia disorders.

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Antipsychotics can be categorized by structure, pharmacologic profile, or class. Because there are so many structurally diverse compounds, classification by structure is difficult. Currently >50 different antipsychotics are available worldwide, with others in various stages of development. A useful method of classifying antipsychotics is according to their relative receptor-binding profiles (Table 174-2).1 In overdose, the clinical toxicity is primarily an exaggerated effect of the pharmacologic activity.

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Table 174-2 Relative Receptor Affinity of Selected Antipsychotics

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