Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis

Mizuno, Yuya, McCutcheon, Robert A., Brugger, Stefan P. and Howes, Oliver D. 2020. Heterogeneity and efficacy of antipsychotic treatment for schizophrenia with or without treatment resistance: a meta-analysis. Neuropsychopharmacology 45 (4) , pp. 622-631. 10.1038/s41386-019-0577-3

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Abstract

Two important clinical questions are whether there is a subtype of schizophrenia which responds differently to clozapine relative to other antipsychotics, and whether greater efficacy of clozapine is dependent on the degree of treatment-resistance. The authors address this by examining both variability and magnitude of response in patients treated with clozapine and other antipsychotics for both treatment-resistant schizophrenia (TRS) and non-resistant schizophrenia. Double-blind randomised controlled trials comparing clozapine with other antipsychotics in patients with schizophrenia were identified using five databases. Standard deviations and means of change in total, positive, and negative symptoms were extracted. Variability ratio (VR) and coefficient of variation ratio (CVR) were used to quantify relative variability in symptom change. Hedges’ g was used to quantify mean differences. Ten TRS studies (n = 822) and 29 non-TRS studies (n = 2566) were meta-analysed. Relative variability in change of total symptoms did not differ significantly between clozapine and other antipsychotics in TRS studies (VR = 1.84; 95%CI, 0.85–4.02). These findings were similar with CVR, and for positive and negative symptoms. Clozapine was superior to other antipsychotics in improving total symptoms in both TRS (g = 0.34; 95%CI, 0.13–0.56) and non-TRS (g = 0.20; 95%CI, 0.08–0.32) studies. Furthermore, clozapine was superior in improving positive symptoms in both study groups, but not for negative symptoms. Pooled effect sizes showed no significant difference between TRS and non-TRS studies. These findings do not support a subtype of schizophrenia which responds specifically to clozapine. Clozapine is more effective than other antipsychotics irrespective of treatment-resistance, arguing for its use more generally in schizophrenia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Additional Information:	This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Publisher:	Springer Nature
ISSN:	0893-133X
Date of First Compliant Deposit:	6 May 2022
Date of Acceptance:	8 November 2019
Last Modified:	08 May 2023 02:53
URI:	https://orca.cardiff.ac.uk/id/eprint/149572

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