Antipsychotic-Induced Weight Gain: Dose-Response Meta-Analysis of Randomized Controlled Trials

作者：Hui Wu, Spyridon Siafis, Tasnim Hamza, Johannes Schneider‐Thoma, John M. Davis, Georgia Salanti, Stefan Leucht · 发表于：Schizophrenia Bulletin · 年份：2022 · DOI：10.1093/schbul/sbac001 · 被引用次数：125 · 研究领域：Schizophrenia research and treatment、Electrolyte and hormonal disorders、Pharmacological Receptor Mechanisms and Effects

BACKGROUND: Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis. METHODS: We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. We estimated the dose-response curves by conducting random-effects dose-response meta-analyses. We used the restricted cubic spline to model the dose-response relationship. The primary outcome was mean weight gain in kg from baseline to endpoint, the secondary outcome was the number of patients with clinically important weight gain. FINDINGS: Ninety-seven studies with 333 dose arms (36 326 participants) provided data for meta-analyses. Most studies were short-term with median duration of 6 weeks (range 4 to 26 weeks). In patients with acute exacerbation, amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone produced mild weight gain in comparison to placebo (mean difference at any dose≤1 kg), while more significant weight gain was observed by all other drugs. For most drugs, dose-response curves showed an initial dose-related increase in weight which plateaued at higher doses, while for others there was no plateau and some even had bell-shaped curves, meaning less ...