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

Author(s)

Elton Diniz ; Lais Fonseca ; Deyvis Rocha ; Alisson Trevizol ; Raphael Cerqueira ; Bruno Ortiz ; André R. Brunoni ; Rodrigo Bressan ^[8] ; Christoph U. Correll ; Ary Gadelha

• Document type: Journal article
• Source: Revista Brasileira de Psiquiatria; v. 45, n. 5, p. 448-458, 2023-11-27.

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. Registration number: PROSPERO CRD42018092033. (AU)

• FAPESP's process: 19/06009-6 - Non-implantable neuromodulation therapies: a perspective for the depressed brain
• Grantee: Geraldo Busatto Filho
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 11/50740-5 - Prevention in schizophrenia and bipolar disorder from neuroscience to the community: a multiphase, multimodal and translational platform for research and intervention
• Grantee: Rodrigo Affonseca Bressan
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/10861-7 - A Phase-I bilateral project using a sham-controlled, factorial design of transcranial direct current stimulation and theta-burst stimulation to investigate the effects on multimodal assessments of prefrontal cortex functioning
• Grantee: Andre Russowsky Brunoni
• Support Opportunities: Regular Research Grants