Selection of atypical antipsychotics for the management of schizophrenia

OBJECTIVE: To review the evidence for selecting one atypical antipsychotic agent over another for management of schizophrenia. DATA SOURCES: A literature search of MEDLINE (1966-June 2003), EMBASE (1998-June 2003), and the Cochrane Library was conducted using the following terms: schizophrenia, quetiapine, ziprasidone, olanzapine, aripiprazole, and risperidone. Bibliographies of relevant articles were hand-searched for additional references. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, blinded trials and meta-analyses that directly or indirectly compared greater than or equal to2 atypical antipsychotic agents in the management of schizophrenia are included in this review. Studies comparing an atypical agent with clozapine are not included. DATA SYNTHESIS: A small number of prospective, randomized, blinded trials that compare efficacy and tolerability of olanzapine and risperidone have been published. These trials did not reveal clinically meaningful differences in efficacy but did confirm that their adverse effect profiles are slightly different (more weight gain with olanzapine and more extrapyramidal reactions with risperidone). Direct comparisons between other atypical antipsychotics are not available. Systematic reviews (indirect comparisons) of placebo-controlled or traditional anti psych otic-control led trials suggest similar efficacy for quetiapine, olanzapine, and risperidone when placebo is the comparator and inferior efficacy of quetiapine compared to olanzapine and risperidone when haloperidol is the comparator. The few available economic analyses are difficult to interpret in light of current practice. CONCLUSIONS: Additional randomized, blinded clinical trials directly comparing efficacy, tolerability, and cost-effectiveness are needed to confirm the proposed differences among atypical antipsychotic agents before recommendations can be made with confidence.