Approaches to mitigate weight gain associated with antipsychotic use

Abstract

Background

Antipsychotics are vital in the management of multiple psychiatric disorders. Weight gain is a common adverse effect that can impact quality of life and long-term adherence to treatment. The goal of this literature review is to explore posited mechanisms for antipsychotic-induced weight gain (AIWG) and review proposed nonpharmacological and pharmacological interventions to mitigate this weight gain.

Methods

An electronic literature search was performed on PubMed to identify full-text, English-language articles that discussed AIWG. Selected articles were published between 2000 and 2024.

Results

Findings from 68 articles were reviewed and discussed. 27 strategies/agents of varying efficacies were identified. Non-pharmacologic interventions exhibit data in being effective against AIWG. Switching to an antipsychotic with a more favorable side-effect profile can be an appropriate option, but it is associated with an increased risk of relapse. Metformin is the most widely accepted and researched adjunctive treatment, followed by liraglutide and samidorphan. Dulaglutide, semaglutide, topiramate, betahistine, amantadine hydrochloride, berberine, probiotics, dietary fiber, nanoparticle formulation, and reboxetine show promising results in the attenuation of AIWG but need further research to understand their efficacy, metabolic effects, and safety. Melatonin, vitamin D, orlistat, modafinil, and naltrexone currently have very little data and have yet to exhibit compelling results. Lorcaserin, rimonabant, and sibutramine have all been removed from the market in the United States and are not recommended.

Conclusion

Data on AIWG is diverse, but scarce. Further research is needed to better understand the pathophysiology of AIWG and explore long-term effectiveness and safety of promising pharmacologic therapies in this vulnerable patient population.