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Meta-Analysis
. 2023 Sep-Oct;45(5):448-458.
doi: 10.47626/1516-4446-2023-3126. Epub 2023 Sep 17.

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Elton Diniz  1 , Lais Fonseca  1 , Deyvis Rocha  1 , Alisson Trevizol  2 , Raphael Cerqueira  1 , Bruno Ortiz  1 , André R Brunoni  3 , Rodrigo Bressan  4 , Christoph U Correll  5 , Ary Gadelha  1
Affiliations
Meta-Analysis

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Elton Diniz et al. Braz J Psychiatry. 2023 Sep-Oct.

Abstract

Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis.

Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%.

Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.

Keywords: Schizophrenia; clozapine; meta-analysis; prevalence; treatment-resistant.

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Conflict of interest statement

RB has received research grants from Janssen Cilag, Novartis, and Roche; has been a forum consultant for Janssen, Novartis, and Roche; and has participated in speaker bureaus for Ache, Janssen, Lundbeck, and Novartis. CUC has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedIn- Cell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris; has provided expert testimony for Janssen and Otsuka; has served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; has received grant support from Janssen and Takeda; has received royalties from UpToDate; and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma, and Quantic. AG has been a consultant and/or advisor to or has received honoraria from Aché, Daiichi-Sankyo, Torrent, Bayer, Cristalia, and Janssen. ARB has received in-kind support from Flow Neuroscience and MagVenture, unrelated to the present study. The other authors report no conflicts of interest.

Figures

Figure 1
Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart. AP = antipsychotic; TRS = treatment-resistant schizophrenia.
Figure 2
Figure 2. Forest plot of treatment-resistant schizophrenia (TRS) prevalence across all studies (intent-to-treat [ITT]; more conservative [MC2]).
See this image and copyright information in PMC

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