Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis.

Authors

Nicolette Stogios, Sri Mahavir Agarwal, Kateryna Maksyutynska, Halima Faisal, Lora Lee Pless, Toby Pillinger, Bailey Humber, Valerie H Taylor, Gary Remington, Guy E J Faulkner, Margaret K Hahn

Published in

JAMA psychiatry. Jul 08, 2026. Epub Jul 08, 2026.

Abstract

Significant weight gain is a concerning adverse effect of antipsychotic medications experienced by patients with schizophrenia spectrum disorders (SSDs). Its high prevalence and significant contribution to cardiometabolic morbidity in this population warrant better consensus on the management of antipsychotic-induced weight gain and related comorbidity.
To evaluate the association between pharmacological interventions and changes in body weight among antipsychotic-treated patients with SSDs.
Ovid MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) Search Portal were searched up to December 5, 2025.
Randomized clinical trials examining any pharmacological intervention for weight reduction in antipsychotic-treated patients with SSDs were included. No restrictions to study duration were applied.
A systematic review and frequentist random-effects network meta-analysis was conducted. Certainty in the evidence was assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. The first round of data analysis took place between May 2025 to November 2025 and was updated in December 2025.
The primary outcome was change in body weight following treatment with pharmacological agent vs placebo or standard care. Secondary outcomes included other anthropometric and metabolic parameters.
A total of 95 studies examining 39 individual pharmacological interventions were included in this review (pooled N = 5898). The network meta-analysis found that semaglutide (mean difference [MD], -10.98 kg; 95% CI, -13.33 to -8.62; k = 3; moderate certainty), liraglutide (MD, -5.43 kg; 95% CI, -8.54 to -2.33; k = 2; moderate certainty), topiramate (MD, -3.95 kg; 95% CI, -5.89 to -2.02; k = 5; moderate certainty), metformin (MD, -3.86 kg; 95% CI, -5.02 to -2.70; k = 16; moderate certainty), and exenatide (MD, -2.97 kg; 95% CI, -5.83 to -0.11; k = 3; moderate certainty) were associated with the most significant reductions in body weight compared to placebo. Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. Clinically meaningful weight change of 5% or greater was observed with semaglutide and metformin. Beneficial effects on other metabolic outcomes were also noted with several of the medications, and there were no major concerns with gastrointestinal adverse effects or leaving the study early (ie, dropouts) between interventions.
This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain.

PMID:
42418179
Bibliographic data and abstract were imported from PubMed on 08 Jul 2026.

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