The Relationship of Pharmacology to Side Effects

Most traditional neuroleptics have a narrow therapeutic-to-toxic index, and thus, the novel antipsychoticsare the result of a search to substantially widen the distance between the dose that treatspsychosis and the one that produces adverse effects. In vitro binding profiles have been created for theatypical antipsychotics that have been approved by the U.S. Food and Drug Administration (FDA)—clozapine, olanzapine, and risperidone and those that are under FDA review—quetiapine and sertindole.These profiles, which were compared with that of the typical neuroleptic haloperidol, provideguidance for predicting the adverse effects produced by these drugs. Most conventional antipsychoticshave central nervous system effects, particularly extrapyramidal symptoms (EPS) and tardive dyskinesia,sedation, and dulling of cognition. Other adverse effects of the typical antipsychotics includethe neuroleptic malignant syndrome, orthostatic hypotension, changes in liver function, anticholinergicand antiadrenergic side effects, sexual dysfunction, and weight gain. The newer agents have alower incidence of EPS and tardive dyskinesia, while weight gain and changes in blood pressure andliver function tests are adverse effects that have been associated with the use of the newer agents. Thefavorable side effect profile of these new antipsychotics is likely to make patients more willing to continuetreatment, and thus these agents represent a step forward in the treatment of patients with severe,chronic mental illness.