CNS Spectrums

Original Research

Efficacy of olanzapine in comparison with clozapine for treatment-resistant schizophrenia: evidence from a systematic review and meta-analyses

Juliano S Souzaa1a3 c1, Monica Kayoa1, Ivson Tassella1, Camila Bertini Martinsa2 and Helio Elkisa1a3

a1 Schizophrenia Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

a2 Institute of Mathematics and Statistics, University of São Paulo, São Paulo, Brazil

a3 Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil

Introduction Clozapine is considered the gold standard for the treatment of patients with treatment-resistant schizophrenia (TRS); however, randomized controlled trials (RCT) of olanzapine showed efficacy similar to clozapine in patients with TRS.

Methods A systematic review was conducted comparing clozapine with olanzapine in patients with TRS. Meta-analyses were performed for single outcome measures. Response to treatment was measured by the percentage of responders, or mean change or endpoint values of psychotic symptoms scales. Effect sizes were shown as relative risks (RR), or standardized mean differences, with 95% confidence intervals.

Findings Seven RCT were included, comprising 648 patients. Five meta-analyses were performed. Olanzapine and clozapine had similar effects on dropout rates (RR = 0.93, CI95% = 0.77–1.12), PANSS total endpoints (SMD = 0.21, CI95% = –0.04–0.46), and PANSS total mean changes (SMD = 0.08, CI95% = –0.01–0.027). Clozapine was superior to olanzapine for PANSS positive (SMD = 0.51, CI95% = 0.17–0.86) and negative (SMD = 0.50, CI95% = 0.16–0.85) subscales. There was a trend toward high doses of olanzapine producing higher effect sizes for this drug.

Conclusions The results of this study suggest that clozapine is significantly more efficacious than olanzapine in improving positive and negative symptoms in TRS patients.

(Received August 30 2012)

(Accepted November 07 2012)

(Online publication December 20 2012)

Key words

  • clozapine;
  • olanzapine;
  • treatment-resistant schizophrenia;
  • meta-analysis;
  • systematic review;
  • schizophrenia


c1 Address for correspondence: Juliano Santos Souza, University of São Paulo Medical School, Projesq–Schizophrenia Program, Rua Ovidio Pires de Campos 785, São Paulo SP-05403-010, Brazil. Email


*  The authors would like to thank Dr. Carlos B. Pereira, Dr. Ricardo Moreno, and Dr. Orestes Forlenza for their valuable critical comments and suggestions for the manuscript, and also Carolina Rehem, for her library assistance.