Chapter 27. Classic Antipsychotic Medications

Henry A. Nasrallah, M.D.; Rajiv Tandon, M.D.
DOI: 10.1176/appi.books.9781585623860.428720



Prior to the introduction of classic antipsychotic medications in the 1950s, treatment for psychotic disorders primarily consisted of humane containment and supportive care. A variety of remedies without empirical support were popular in different cultures for brief periods of time but went out of vogue because they were ineffective. One approach to the treatment of psychosis that survived through the ages was the use of reserpine as a folk medicine in India. In the Ayurveda (the traditional Indian medical system originating 5,000 years ago), Sarpagundha (Rauwolfia serpentina, or Indian snakeroot, from which reserpine is derived) was recommended as the treatment for "unmada" (psychosis). In the early 1950s, reserpine was found to improve psychosis and reduce violent behavior in clinical trials among aggressive mentally ill patients in state hospitals in New York and California, and this led to its introduction as an antipsychotic in 1954 (2 years after chlorpromazine). However, reserpine's popularity declined after 1957 because of its high level of side effects and low safety index. Although the use of reserpine has been completely discontinued in some countries (e.g., the United Kingdom) because of its significant drug interactions and adverse effects, it is available in the United States, where it is still used, albeit very infrequently, as an alternative or augmentation treatment in patients with schizophrenia refractory to other antipsychotic treatment.

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FIGURE 27–1. Chemical structures of various classic antipsychotics.

FIGURE 27–2. Dopaminergic pathways of the brain.

FIGURE 27–3. Clinical benefits of low extrapyramidal side effect (EPS) risk.

FIGURE 27–4. Dose–response curves of classic versus atypical antipsychotic agents for antipsychotic effects versus extrapyramidal side effects.Source. Adapted from Jibson and Tandon 1998.
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TABLE 27–1. First-generation antipsychotics (n = 51)
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TABLE 27–2. Comparison of CUtLASS band I and CATIE phase I
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TABLE 27–3. Relative affinities of classic antipsychotics to various neurotransmitter receptors
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TABLE 27–4. Clinical implications of blockade of different receptors
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TABLE 27–5. Incidence of adverse reactions to classic antipsychotics at therapeutic doses


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Which of the following first-generation antipsychotics belongs to the piperidine phenothiazine class of agents?
Haloperidol, the best-known classic antipsychotic, belongs to which of the following classes of first-generation antipsychotics?
It is believed that D2 blockade of various dopaminergic systems represents the putative mechanism of action of conventional antipsychotics. An adverse effect associated with D2 receptor antagonism in the mesocortical dopaminergic pathway is
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