Efficacy of newer generation antipsychotics in the treatment of schizophrenia.

The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy between risperidone, olanzapine, and quetiapine, there are clear differences in their side-effect profiles and these are briefly summarized. Copyright 2002 Elsevier Science Ltd.