Antipsychotic Drugs in Schizophrenia: Relative Effects in Patients With and Without Treatment Resistance

How antipsychotic drugs compare in schizophrenia, and especially in medication-refractory schizophrenia, is a subject of considerable interest. Two network meta-analyses and 1 direct comparison meta-analysis recently compared antipsychotics in schizophrenia patients with and without documented treatment resistance. One network meta-analysis of antipsychotic drugs in non-refractory patients found clear efficacy advantages for clozapine, amisulpride, olanzapine, and risperidone. One network meta-analysis of antipsychotic drugs in refractory patients found a clear efficacy advantage for olanzapine; surprisingly, in this meta-analysis, clozapine was superior to first-generation but not second-generation antipsychotics. One direct comparison meta-analysis found clozapine generally superior to first- and second-generation antipsychotics, with advantages more clearly apparent in studies that were 3 months in duration or less. Drug discontinuation and adverse effect data from these meta-analyses are presented, and issues arising from the results are briefly discussed. At the risk of oversimplification, it appears that clozapine retains its preeminence in medication-refractory schizophrenia and that clozapine and olanzapine are both associated with superior efficacy outcomes in non-refractory patients. Interestingly, haloperidol, generally considered a reference neuroleptic and a reference comparator drug, fared poorly in most comparisons.