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Review
. 2024 Jan 1;181(1):26-38.
doi: 10.1176/appi.ajp.20230922.

Psychotropic Drug-Related Weight Gain and Its Treatment

Roger S McIntyre  1 , Angela T H Kwan  1 , Joshua D Rosenblat  1 , Kayla M Teopiz  1 , Rodrigo B Mansur  1
Affiliations
Review

Psychotropic Drug-Related Weight Gain and Its Treatment

Roger S McIntyre et al. Am J Psychiatry. .

Abstract

Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.

Keywords: Adverse Effects of Medication; Anticonvulsants; Antidepressants; Antipsychotics; Glucagon-Like Peptide-1 Agonists; Psychotropic Drug-Related Weight Gain.

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Conflict of interest statement

Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China; he has received speaker or consultation fees from AbbVie, Alkermes, Atai Life Sciences, Axsome, Bausch Health, Biogen, Boehringer Ingelheim, Eisai, Intra-Cellular, Janssen, Kris, Lundbeck, Mitsubishi Tanabe, Neumora Therapeutics, Neurawell, Neurocrine, NewBridge Pharmaceuticals, Novo Nordisk, Otsuka, Pfizer, Purdue, Sage, Sanofi, Sunovion, Takeda, and Viatris; and he is CEO of Braxia Scientific Corp. Dr. Rosenblat has received research grant support from the American Psychiatric Association, American Society of Psychopharmacology, Brain and Cognition Discovery Foundation, Canadian Cancer Society, Canadian Institute of Health Research, Canadian Psychiatric Association, Joseph M. West Family Memorial Fund, Labatt Brain Health Network, Physician Services Inc. Foundation, University Health Network Center for Mental Health, and University of Toronto; he has received speaker, consultation, or research fees from Allergan, Boehringer Ingelheim, COMPASS, iGan, Janssen, Lundbeck, and Sunovion; and he was previously the chief medical and scientific officer of Braxia Scientific Corp. Ms. Teopiz has received fees from Braxia Scientific Corp. The other authors report no financial relationships with commercial interests.

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