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

Hui Wu, Spyridon Siafis, Tasnim Hamza, Johannes Schneider-Thoma, John M Davis, Georgia Salanti, Stefan Leucht

Schizophrenia bulletin 2022 May 07

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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. 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. 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 weight gain to be associated with higher doses. Second-generation antipsychotics do not only differ in their propensity to produce weight gain, but also in the shapes of their dose-response curves. This information is important for dosing decisions in clinical practice. © The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Citation

Hui Wu, Spyridon Siafis, Tasnim Hamza, Johannes Schneider-Thoma, John M Davis, Georgia Salanti, Stefan Leucht. Antipsychotic-Induced Weight Gain: Dose-Response Meta-Analysis of Randomized Controlled Trials. Schizophrenia bulletin. 2022 May 07;48(3):643-654