Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics.

OBJECTIVE To review the efficacy of placebo in comparison with atypical and typical antipsychotics for the treatment of schizophrenia and schizoaffective disorder and to evaluate the pertinence of using placebo in clinical trials with antipsychotics. METHOD Trials in which the atypical antipsychotics were compared with typical antipsychotics and placebo were included. A search was conducted using the terms 'amisulpride', 'aripiprazole', 'clozapine', 'olanzapine', 'quetiapine', 'risperidone', 'sertindole', 'ziprasidone' and 'zotepine'. Main efficacy parameters were calculated using the proportion of 'events' (defined as a deterioration or lack of improvement by at least 20% in Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale) and the pooled relative risk with random effects, with their respective 95% confidence intervals. We also calculated the necessary sample sizes in studies in which the study drug is compared to a typical antipsychotic or placebo. RESULTS The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. CONCLUSIONS Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.