The new and evolving pharmacotherapy of schizophrenia

Based on the evidence presented here, the following tentative conclusions can be drawn. Atypical antipsychotics (except amisulpride) have shown superiority over placebo in acute schizophrenia. Compared with conventional antipsychotics, they are at least as effective. Generally, analyses employing conservative criteria (e.g., Cochrane reviews) report few efficacy differences between atypical and conventional agents. There are now many well-controlled studies indicating modest advantages for the atypical antipsychotics, however, particularly in specific symptom domains. For the treatment of negative symptoms, olanzapine and to a lesser extent amisulpride seem most promising. Risperidone, olanzapine, and quetiapine display advantages in improving cognitive and depressive symptoms. There are indications that the atypical antipsychotics are associated with decreased likelihood of rehospitalization and improved quality of life. In head-to-head comparisons of atypical antipsychotics, none have shown consistent efficacy advantages. In severely refractory samples, no atypical antipsychotics have consistently been shown to be as effective as clozapine or superior to conventional agents. There are indications, however, that risperidone, olanzapine, and quetiapine have advantages over conventional agents in less severely refractory patients. Few maintenance RCTs have been published, and efficacy advantages for atypical antipsychotics in prospective RCTs in first-episode schizophrenia have not been reported.