The trajectory of sedative adverse events caused by antipsychotics: a meta-analysis of individual participant data from randomised, placebo-controlled, clinical trials in acute phase schizophrenia

作者：Nobuyuki Nomura, Spyridon Siafis, Johannes Schneider‐Thoma, Lasse Brandt, Jin‐Young Park, Orestis Efthimiou, Josef Priller, John M. Davis, Hiroyoshi Takeuchi, Stefan Leucht · 发表于：The Lancet Psychiatry · 年份：2025 · DOI：10.1016/s2215-0366(25)00025-2 · 被引用次数：10 · 研究领域：Schizophrenia research and treatment、Intensive Care Unit Cognitive Disorders、Healthcare Decision-Making and Restraints

BACKGROUND: Sedative adverse events are common in patients with schizophrenia undergoing antipsychotic treatment, which affects treatment adherence and the patients' quality of life. Although tolerance to sedation is believed to develop, robust evidence documenting the timing of sedation onset and resolution remains elusive. To address this gap, we aimed to assess the dynamics of onset and resolution of sedation across various antipsychotics in patients with schizophrenia. METHODS: In this meta-analysis, we included placebo-controlled, randomised controlled trials (RCTs) of antipsychotic monotherapy for the acute phase of schizophrenia and schizoaffective disorder. We searched PubMed for RCTs from inception until May 6, 2021 and obtained individual participant data of included trials through the Yale University Open Data Access project. We created Kaplan-Meier curves to assess the probability of onset of sedation and resolution from the incidence of sedation across time after treatment initiation. People with lived experience were not involved in this study. This study is registered with PROSPERO, CRD42022351647. FINDINGS: We included a total of 6791 participants (4549 [67·0%] men and 2242 [33·0%] women, with a mean age of 38·0 years [SD 12·4, range 13-81], 1172 [17·3%] were Asian, 1626 [23·9%] were Black, 3654 [53·8%] were White, and 339 [5·0%] were other ethnicities) from 19 RCTs. Sedative adverse events were observed in 582 (8·6%) of 6791 participants and typically occurre...