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The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study.

A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments.

Overall, 74 percent of patients discontinued the study medication before 18 months (1061 …