Evidence of clozapine's effectiveness in schizophrenia: A systematic review and meta-analysis of randomized trials

Objective: The purpose of this study was to evaluate all available trial-ba sed evidence on the effectiveness of clozapine in schizophrenia as compared with conventional neuroleptics. Method: All randomized, controlled trials comparing clozapine with a conventional neuroleptic in which there was sati sfactory concealment of patients' treatment allocation were located through electronic searches in ail languages of several databases and through cont acting authors of recent trials as well as the manufacturer of clozapine. A t least two independent reviewers assessed trials for inclusion in the stud y and extracted data for meta-analysis. Results: The review included 2,530 randomly assigned participants in 30 trials, most of them short-term. Cloza pine-treated patients showed more clinical improvement and experienced sign ificantly fewer relapses during treatment, although the risk of blood dyscr asias in long-term treatment may be as high as 7%. Scores on symptom rating scales showed greater improvement among clozapine-treated patients, who we re also more satisfied with their treatment. However, there was no evidence that the superior clinical effect of clozapine is reflected in levels of f unctioning; on the other hand, global functional and pragmatic outcomes wer e frequently not reported. Clinical improvement was most pronounced in pati ents with treatment-resistant illness. Conclusions: This metaanalysis confi rms that clozapine is more effective than conventional neuroleptics in redu cing symptoms of patients with both treatment-resistant and nonresistant sc hizophrenia. Future trials should be long-term pragmatic community trials o r should address the effectiveness of clozapine in special patient populati ons. An international standard set of outcomes, including pragmatic assessm ents of functioning, would greatly enhance the comparison and summation of trials and future assessments of effectiveness.