A systematic review and meta-analysis of clozapine response rates in schizophrenia
- Forfatter(e)
- Samara, M., Glarou, E., Pinioti, E., Nikolakopoulou, A., Siafis, S., Christodoulou, N., Leucht, S., Lappas, A. S.
- År
- 2026
- Tidsskrift
- Nature Mental Health
- Volum
- 4
- Sider
- 14
- Kategori(er)
- Psykose
- Tiltakstype(r)
- Antipsykotika
- Abstract
Clozapine is the gold standard for treatment-resistant schizophrenia (TRS) and demonstrates superior efficacy in non-TRS. Clozapine response rates have been quantified in TRS, but comparable data for non-TRS groups are sparse. Here we conducted a single-group meta-analysis of randomized controlled trials evaluating clozapine monotherapy efficacy across the schizophrenia spectrum, irrespective of treatment resistance. Primary outcomes included response rates (>= 20% Positive and Negative Syndrome Scale (PANSS) reduction) and absolute/percentage PANSS score changes. Secondary analyses examined >= 50% PANSS reduction rates, author-defined remission criteria and imputed response rates across multiple thresholds (0-75% reduction). Meta-regression and subgroup analyses explored the impact of predefined variables. Sixty randomized controlled trials were included: 27 in non-TRS patients and 33 in TRS. In non-TRS, we found an 81% response rate (95% confidence interval (CI) 69% to 89%), with mean PANSS reductions of 31.1 points (95% CI -38.0 to -24.2), representing a 48.3% improvement (95% CI -57.9% to -38.7%). In TRS, we found a 63% response rate (95% CI 56% to 69%), with mean reductions of 22.4 PANSS points (95% CI -27.4 to -17.4) equating to 31.3% improvement (95% CI -37.1% to -25.6%). Studies with a longer illness duration showed a nonlinear association with worse outcomes. Response declined steeply in the first illness decade (odds ratio 0.80 per year, 95% CI 0.71 to 0.91), from >90% at illness onset to similar to 46% by year 10, before stabilizing with no further time-dependent effects. This meta-analysis provides robust evidence for clozapine's efficacy across all stages of schizophrenia. The duration-of-illness effect underscores the importance of prompt treatment initiation. Clinicians and researchers should consider clozapine earlier in the treatment algorithm and maintain therapeutic optimism even in chronic cases, as substantial response rates persist.