Comparative efficacy of antipsychotics in the treatment of schizophrenia: a critical assessment

Because of their broader spectrum of efficacy and lower risk of short- and long-term motor side-effects in comparison to first generation 'typical' antipsychotics (FGAs), second generation 'atypical' antipsychotics (SGAs) are rapidly becoming the standard of antipsychotic pharmacotherapy. It is unclear, however, as to how different SGAs compare in efficacy since the multitude of studies and integrative reviews seemingly provide discrepant information in this regard. To address this issue, we critically review three distinct approaches to analysis of data from randomized controlled clinical trials of the efficacy of SGAs in the treatment of schizophrenia and schizoaffective disorder: (i) comparing average improvement in symptomatology with different SGAs; (ii) comparing average improvement observed with different SGAs relative to haloperidol; and (iii) head-head trials comparing one SGA to another. We discuss the strengths and limitations of each approach with reference to the reports in which it was applied to assess comparative antipsychotic efficacy. We conclude that the most informative picture is obtained by using each of these strategies, looking at all available data, and then putting all the results together. Data thus far do not support claims of differential efficacy among SGAs with the singular exception of clozapine possibly still being the gold standard of antipsychotic efficacy in otherwise treatment-refractory schizophrenia. Dosing appears to be a critical variable in optimizing efficacy.