Metabolic Effects of the Atypical Antipsychotics

Authors: James Wooten, PharmD


The atypical antipsychotic drugs are mainstays in the treatment of various psychiatric disorders. These newer, second generation agents include clozapine (Clozaril), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify). The newer atypical agents are thought to be as effective as the older, phenothiazine-type antipsychotics and generally better tolerated. These older agents include many drugs, such as haloperidol (Haldol), fluphenazine (Prolixin), and thiothixene (Navane). The “atypical” nature with these new agents generally refers to the varied mechanism these agents have compared with the older, phenothiazine-type drugs. The atypical antipsychotics, to varying degrees, possess the ability to both antagonize the dopamine-2 receptor, as well as the serotonin 5-HT2A receptor, while the older phenothiazines primarily affect only the dopamine receptor. This dual mechanism of the atypical antipsychotics may contribute to their effectiveness in treating a wide variety of psychiatric disturbances, including schizophrenia, acute mania, bipolar mania, psychotic agitation, and bipolar maintenance. Clinical research has demonstrated the effectiveness of these second generation agents, but whether they are always safer than the older phenothiazines is debatable. Their use has been supplanted by the atypical antipsychotics, primarily because the older agents are thought to cause a higher incidence of extrapyramidal side effects and potentially permanent tardive dyskinesia. Now there are reports of serious side effects with the atypical antipsychotics, such that physicians must understand the potential risks these drugs may pose to their patients.1–6

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1. Food and Drug Administration Center for Drug Evaluation and Research. Available athttp://www.fda.gov/cder/index.html. Accessed April 23, 2007.
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