The CATIE schizophrenia trial: Results, impact, controversy

The CATIE (Clinical Antipsychotic Trials for Intervention Effectiveness) Schizophrenia Trial was designed to examine fundamental issues about second-generation antipsychotic (SGA) medications (olanzapine, risperidone, quetiapine, and ziprasidone)-their relative effectiveness and their effectiveness compared to a first-generation antipsychotic (FGA), perphenazine. This article reviews these and other findings from this important trial and offers a perspective regarding their meaning for practice and their significance for the advancement of research in psychiatry. The primary outcome measure, time to discontinuation, served as an index of effectiveness and was remarkably short; only 26% of subjects completed the 18-month trial on the medicine to which they were initially randomized. Subjects receiving olanzapine experienced a slightly longer time to discontinuation. Based on this single criterion, olanzapine showed greater effectiveness than the other agents despite its association with significant metabolic disturbance, especially weight gain. Perphenazine unexpectedly showed comparable levels of effectiveness and produced no more extrapyramidal side effects than the other agents. Despite modest prolactin elevation, risperidone was the best-tolerated medication. Ziprasidone was associated with weight loss and with positive impact on lipids and blood glucose. In Phase 2, clozapine demonstrated better effectiveness compared to other SGAs for subjects who discontinued their Phase 1 medication because of efficacy. Olanzapine and risperidone showed greater effectiveness in the tolerability pathway. CATIE secondary outcomes are currently being examined. Improvements in cognition were modest among all the agents in Phase 1, and perphenazine was no less effective in improving cognitive performance than the SGAs. Cost-effectiveness analysis revealed a significant advantage for perphenazine, due to the impact of the high-priced, brand-name SGAs on overall health care costs.