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Because of its side-effect profile, clozapine is the only available antipsychotic that should not be administered as a first-line agent for schizophrenia or schizoaffective disorder. However, this does not mean that clozapine is ineffective in these disorders. Early trials comparing clozapine with haloperidol and chlorpromazine indicated that clozapine was at least as effective as the other agents for acutely psychotic patients. In the chlorpromazine comparison (Fischer-Cornelssen and Ferner 1976), the advantages were most apparent for the more severely ill patients. The comparison with haloperidol (Honigfeld et al. 1984) was carried out in a more severely ill group of patients and found a substantial advantage for clozapine. A report by Shopsin et al. (1979) compared clozapine, chlorpromazine, and placebo in 31 newly admitted patients with acute illness. Clozapine was found to be superior to both chlorpromazine and placebo. Taken together, these early studies indicate that clozapine is effective for treatment of a broad range of individuals with acute psychosis. In China, for example, clozapine is commonly prescribed as a first-line antipsychotic for acute schizophrenia.

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