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Meta-Analysis
. 2018 Oct;138(4):281-288.
doi: 10.1111/acps.12954. Epub 2018 Sep 14.

Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis

C Okhuijsen-Pfeifer  1 , E A H Huijsman  1 , A Hasan  2 , I E C Sommer  3 , S Leucht  4 , R S Kahn  1   5 , J J Luykx  1   6   7   8
Affiliations
Meta-Analysis

Clozapine as a first- or second-line treatment in schizophrenia: a systematic review and meta-analysis

C Okhuijsen-Pfeifer et al. Acta Psychiatr Scand. 2018 Oct.

Abstract

Objective: No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta-analysis therefore focus on the use of clozapine as first-line or second-line treatment in non-treatment-resistant patients.

Methods: Articles were eligible if they investigated clozapine compared to another antipsychotic as a first- or second-line treatment in non-treatment-resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random-effects meta-analyses.

Results: Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta-analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges' g = 0.220, P = 0.026, 95% CI = 0.026-0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges' g = 0.274, P = 0.030, 95% CI = 0.027-0.521).

Conclusion: The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first- or second-line treatment. Only large clinical trials may comprehensively probe disease stage-dependent superiority of clozapine and investigate overall tolerability.

Keywords: antipsychotics; first-episode; meta-analysis; schizophrenia.

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Figures

Figure 1
Figure 1
Flow diagram of the systematic review and meta‐analyses selection process.
Figure 2
Figure 2
(a) Forest plot showing meta‐analytic results of response to clozapine vs. other antipsychotics. Squares (whiskers represent 95% confidence intervals) indicate the effect sizes of the individual studies. The size of the squares reflects the sample size of each individual study. Diamonds represent summary statistics. CI, confidence interval; other AP, risperidone/chlorpromazine/thioridazine; CLZ, clozapine. (b) Forest plot showing meta‐analytic results of response to clozapine vs. risperidone. Squares (whiskers represent 95% confidence intervals) indicate the effect sizes of the individual studies. The size of the squares reflects the sample size of each individual study. Diamonds represent summary statistics. CI, confidence interval; RISP, risperidone; CLZ, clozapine. [Colour figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

Comment in

  • Clozapine as an early-stage treatment.
    Homan P, Kane JM. Homan P, et al. Acta Psychiatr Scand. 2018 Oct;138(4):279-280. doi: 10.1111/acps.12965. Acta Psychiatr Scand. 2018. PMID: 30240545 No abstract available.

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