Next-step treatment for schizophrenia non-responsive to antipsychotics: a systematic review and network meta-analysis

作者：Yuki Furukawa, Nurul Husna Salahuddin, Yaohui Wei, Elisavet Pinioti, David D. Kim, Filip Milosavlijević, Spyridon Siafis, Johannes Schneider-Thoma, Myrto Samara, Irene Bighelli, Stefan Leucht · 发表于：EClinicalMedicine · 年份：2026 · DOI：10.1016/j.eclinm.2026.103988 · 研究领域：Schizophrenia research and treatment、Meta-analysis and systematic reviews、Treatment of Major Depression

Background: Antipsychotics are often insufficient for schizophrenia, but the optimal next-step strategies for non-response remain uncertain. Guidelines recommend some pharmacological, psychological, and non-invasive brain stimulation (NIBS) approaches, but we do not know which one works best. We summarized current evidence for schizophrenia non-responsive to antipsychotics. Methods: We searched the Cochrane Schizophrenia Group registry (up till January 13, 2025), and PubMed up till January 8, 2026 for randomized controlled trials (RCTs) of patients non-responsive to prior antipsychotic treatment, with persistent symptoms after at least one adequate 4-week antipsychotic trial. Raters needed to be masked. The primary outcome was change in overall symptoms analyzed using random-effects network meta-analyses of standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was pre-registered (https://osf.io/wcs5d/). Findings: Fifty-nine RCTs (5409 participants; mean age 39.8 years; 3416 men, 1441 women) were included; 5013 contributed to the primary analysis. Antipsychotic combination therapy (k = 18; n = 575; SMD -0.25, 95% CI -0.46 to -0.04; CINeMA: very low) and electroconvulsive therapy (ECT; k = 5; n = 97; SMD -0.51, -0.96 to -0.06; very low) might be more efficacious than continuing the same antipsychotic. Cognitive behavioral therapy for psychosis (CBTp) showed weak evidence of benefit over continuing the same antipsychotic (k = 5; n = 340; SMD -0.2...