Efficacy and tolerability of pharmacological interventions for schizophrenia non-responsive to prior treatment: a systematic review and network meta-analysis

作者：Myrto Samara, Andreas S. Lappas, Elisavet Pinioti, Eleni Glarou, Iwo Fober, Christos Christogiannis, Spyridon Siafis, Nikos Christodoulou, Bartosz Helfer, Dimitris Mavridis, Stefan Leucht · 发表于：EClinicalMedicine · 年份：2025 · DOI：10.1016/j.eclinm.2025.103291 · 被引用次数：11 · 研究领域：Schizophrenia research and treatment、Treatment of Major Depression、Meta-analysis and systematic reviews

Background: Treatment-resistant schizophrenia (TRS) poses significant challenges for both clinicians and patients. This systematic review and network meta-analysis (NMA) aimed to compare the efficacy and tolerability of all available pharmacotherapy options. Methods: We systematically searched MEDLINE, Cochrane Central, Embase, PsycINFO, ClinicalTrials.gov, WHO trials registry, and FDA website through March 2025 for randomised controlled trials (RCTs) comparing pharmacological treatments for TRS. NMA estimated pooled effects, with the primary outcome being overall symptom change. Secondary outcomes included treatment response, individual symptom domains, discontinuation, adverse events, quality of life, and functioning. Effect sizes were reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes, with 95% confidence intervals (CIs). Meta-regression and sensitivity analyses explored variability in findings. Findings: 150 RCTs with 11,375 patients examined 78 drug options or placebo. Clozapine showed superior efficacy for overall symptoms compared to haloperidol, chlorpromazine, quetiapine, and sulpiride (SMDs 0.35 to 1.00). It slightly outperformed olanzapine for positive symptoms (SMD 0.19; 95% CI 0.00 to 0.37) and risperidone for response rates (OR 0.64; 95% CI 0.41 to 1.01). Clozapine combinations with amisulpride, duloxetine, memantine, mirtazapine, topiramate, and ziprasidone improved overall symptoms more than ...