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Developed starting in the 1950s, the typical antipsychotics are effective against the positive signs of psychosis (e.g., delusions, hallucinations, disorganized thought), but they provided no treatment for the negative signs (e.g., avolition, alogia, social withdrawal). In addition, numerous adverse side effects associated with these agents lead to poor patient compliance. The second-generation drugs, or atypical antipsychotics, have been available starting in the 1990s. These drugs are characterized by minimal extrapyramidal side effects when taken at effective dosages and have activity against the negative signs of schizophrenia (Table 180-1). Third-generation agents are being developed to minimize the adverse side effects seen with the first- and second-generation agents.

TABLE 180-1Common Antipsychotics

Antipsychotics were originally referred to as major tranquilizers, because of their ability to calm patients, but 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's syndrome, Huntington's chorea, and basal ganglia disorders.


Currently more than 50 different antipsychotics are available worldwide. Classification by structure is difficult; a more useful method is classification according to their relative receptor-binding profiles (Table 180-2).1 In overdose, the clinical toxicity is primarily an exaggerated effect of the pharmacologic activity.

TABLE 180-2Relative Receptor Affinity of Selected Antipsychotics

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