The Roles of Efficacy, Safety, and Tolerability in Antipsychotic Effectiveness: Practical Implications of the CATIE Schizophrenia Trial

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) series of studies has set a standard for trials in schizophrenia. Included in the 3-phase National Institute of Mental Health-sponsored series were 1460 patients drawn from 57 sites in 24 states. This was designed as a “real-world”practical clinical trial, including a broad array of patients and asking straightforward, clinically relevant questions. The primary aim was to compare the available atypical agents olanzapine, quetiapine, risperidone, and ziprasidone—to each other and to the typical agent perphenazine—with regard to drug effectiveness and tolerability. In general, the various agents studied were similar, with olanzapine being relatively the most effective, as measured by treatment discontinuation. This might be due in part to the more optimal dosing of olanzapine compared with the other antipsychotics. In the study arm that included clozapine, that agent was shown to be more effective than olanzapine, quetiapine, or risperidone. Perphenazine tended to perform as well as the atypical agents. Except for clozapine, olanzapine clearly had the greatest metabolic side effect burden, and ziprasidone, the least. Perphenazine had the most motor side effects, although the rate was modest.