Antipsychotic-Induced Obesity: A Literature Review of Pathophysiology, Genetics, and Management Strategies
DOI:
https://doi.org/10.12775/QS.2026.66.74166Keywords
obesity, schizophrenia, psychotic disorders, antipsychotic drugs, mechanism, treatmentAbstract
Background: Obesity is a highly prevalent issue observed in individuals with psychiatric disorders undergoing antipsychotic therapy. It adversely impacts health outcomes. Consequently, it elevates the risk of relapse of the primary psychiatric condition and substantially shortens life expectancy.
Aim of the study: This study aims to review current literature regarding obesity among individuals treated with neuroleptics, analyzing data on its etiology, pathophysiology, and physical/mental health complications, alongside therapeutic management strategies.
Material and methods: This article comprises a comprehensive literature review encompassing recent experimental, observational, and meta-analytic studies focused on antipsychotic-induced obesity. We analyzed data regarding the somatic and psychiatric ramifications of obesity, the effects of neuroleptics on body mass, the role of genetic factors in drug-induced weight gain, and treatment modalities.
Results and conclusions: The literature review demonstrates that obesity severely impacts physical health, precipitates metabolic disturbances, and worsens psychiatric outcomes. Antipsychotic-induced weight gain stems from the interaction of psychotropic substances with specific neural receptors, amplified by genetic susceptibility related to receptor gene polymorphisms. Among non-pharmacological interventions, behavioral therapy yields favorable outcomes. GLP-1 receptor agonists appear effective for long-term weight loss, while transitioning antipsychotic therapy to third-generation neuroleptics serves as another beneficial strategy. In each of the above-mentioned therapies, physical activity and diet were used as the basic treatment.
References
1. Allison, D. B., Mentore, J. L., Heo, M., Chandler, L. P., Cappelleri, J. C., Infante, M. C., & Weiden, P. J. (1999). Antipsychotic-induced weight gain: a comprehensive research synthesis. American journal of Psychiatry, 156(11), 1686-1696. https://doi.org/10.1176/ajp.156.11.1686
2. Rubino, F., Cummings, D. E., Eckel, R. H., Cohen, R. V., Wilding, J. P., Brown, W. A., ... & Mingrone, G. (2025). Definition and diagnostic criteria of clinical obesity. The Lancet Diabetes & Endocrinology, 13(3), 221-262. https://doi.org/10.1016/s2213-8587(24)00316-4
3. Després, J. P. (2001). Health consequences of visceral obesity. Annals of medicine, 33(8), 534-541. https://doi.org/10.3109/07853890108995963
4. Świerczyńska, B., Sekuła, M., Smoluchowski, K., Suchodolska, M., & Undziakiewicz, A. (2020). Mechanisms linking obesity and gastrointestinal cancers. Journal of Education, Health and Sport, 10(8), 346–354. https://doi.org/10.12775/JEHS.2020.10.08.041
5. McWhinney, S., Kolenic, M., Franke, K., Fialova, M., Knytl, P., Matejka, M., ... & Hajek, T. (2021). Obesity as a risk factor for accelerated brain ageing in first-episode psychosis—a longitudinal study. Schizophrenia bulletin, 47(6), 1772-1781. https://doi.org/10.1093/schbul/sbab064
6. Simon, G. E., Von Korff, M., Saunders, K., Miglioretti, D. L., Crane, P. K., Van Belle, G., & Kessler, R. C. (2006). Association between obesity and psychiatric disorders in the US adult population. Archives of general psychiatry, 63(7), 824-830. https://doi.org/10.1001/archpsyc.63.7.824
7. Dąbrowska, J., Wójcik, M., Samek, I., Jańczyk, M., Bator, D., & Milanowska, J. (2020). Obesity and mental health. Journal of Education, Health and Sport, 10(6), 199–205. https://doi.org/10.12775/JEHS.2020.10.06.022
8. Bazo-Alvarez, J. C., Morris, T. P., Carpenter, J. R., Hayes, J. F., & Petersen, I. (2020). Effects of long-term antipsychotics treatment on body weight: A population-based cohort study. Journal of Psychopharmacology, 34(1), 79-85. https://doi.org/10.1177/0269881119885918
9. Gebhardt, S., Theisen, F. M., Haberhausen, M., Heinzel-Gutenbrunner, M., Wehmeier, P. M., Krieg, J. C., Kühnau, W., Schmidtke, J., Remschmidt, H., & Hebebrand, J. (2010). Body weight gain induced by atypical antipsychotics: an extension of the monozygotic twin and sib pair study. Journal of clinical pharmacy and therapeutics, 35(2), 207–211. https://doi.org/10.1111/j.1365-2710.2009.01084.x
10. McCarthy, S., Mottagui-Tabar, S., Mizuno, Y., Sennblad, B., Hoffstedt, J., Arner, P., Wahlestedt, C., & Andersson, B. (2005). Complex HTR2C linkage disequilibrium and promoter associations with body mass index and serum leptin. Human genetics, 117(6), 545–557. https://doi.org/10.1007/s00439-005-1328-6
11. Opgen-Rhein, C., Brandl, E. J., Müller, D. J., Neuhaus, A. H., Tiwari, A. K., Sander, T., & Dettling, M. (2010). Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics, 11(6), 773–780. https://doi.org/10.2217/pgs.10.50
12. Yevtushenko, O. O., Cooper, S. J., O'Neill, R., Doherty, J. K., Woodside, J. V., & Reynolds, G. P. (2008). Influence of 5-HT2C receptor and leptin gene polymorphisms, smoking and drug treatment on metabolic disturbances in patients with schizophrenia. The British journal of psychiatry : the journal of mental science, 192(6), 424–428. https://doi.org/10.1192/bjp.bp.107.041723
13. Vehof, J., Risselada, A. J., Al Hadithy, A. F., Burger, H., Snieder, H., Wilffert, B., Arends, J., Wunderink, L., Knegtering, H., Wiersma, D., Cohen, D., Mulder, H., & Bruggeman, R. (2011). Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication. Psychopharmacology, 216(2), 257–265. https://doi.org/10.1007/s00213-011-2211-x
14. Wang, Y. C., Bai, Y. M., Chen, J. Y., Lin, C. C., Lai, I. C., & Liou, Y. J. (2005). Polymorphism of the adrenergic receptor alpha 2a -1291C>G genetic variation and clozapine-induced weight gain. Journal of neural transmission (Vienna, Austria : 1996), 112(11), 1463–1468. https://doi.org/10.1007/s00702-005-0291-7
15. Lencz, T., Robinson, D. G., Napolitano, B., Sevy, S., Kane, J. M., Goldman, D., & Malhotra, A. K. (2010). DRD2 promoter region variation predicts antipsychotic-induced weight gain in first episode schizophrenia. Pharmacogenetics and genomics, 20(9), 569–572. https://doi.org/10.1097/FPC.0b013e32833ca24b
16. Herken, H., Erdal, M., Aydin, N., Sengul, C., Karadag, F., Barlas, O., & Akin, F. (2009). The association of olanzapine-induced weight gain with peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism in patients with schizophrenia. DNA and cell biology, 28(10), 515–519. https://doi.org/10.1089/dna.2009.0893
17. Wang, Y. C., Bai, Y. M., Chen, J. Y., Lin, C. C., Lai, I. C., & Liou, Y. J. (2005). C825T polymorphism in the human G protein beta3 subunit gene is associated with long-term clozapine treatment-induced body weight change in the Chinese population. Pharmacogenetics and genomics, 15(10), 743–748. https://doi.org/10.1097/01.fpc.0000175600.26893.fa
18. Ruaño, G., Goethe, J. W., Caley, C., Woolley, S., Holford, T. R., Kocherla, M., Windemuth, A., & de Leon, J. (2007). Physiogenomic comparison of weight profiles of olanzapine- and risperidone-treated patients. Molecular psychiatry, 12(5), 474–482. https://doi.org/10.1038/sj.mp.4001944
19. Seeger, T.F., Seymour, P.A., Schmidt, A.W., Zorn, S.H., Schulz, D.W., Lebel, L.A., Mclean, S., Guanowsky, V., Howard, H.R., & Lowe, J. (1995). Ziprasidone (CP-88,059): a new antipsychotic with combined dopamine and serotonin receptor antagonist activity. The Journal of pharmacology and experimental therapeutics, 275 1, 101-13 . https://doi.org/10.1016/s0022-3565%2825%2912023-5
20. Kalarchian, M. A., Marcus, M. D., Levine, M. D., Haas, G. L., Greeno, C. G., Weissfeld, L. A., & Qin, L. (2005). Behavioral treatment of obesity in patients taking antipsychotic medications. Journal of Clinical Psychiatry, 66(8), 1058-1063. https://doi.org/10.4088/jcp.v66n0815
21. Werneke, U., Taylor, D., & Sanders, T. A. B. (2002). Options for pharmacological management of obesity in patients treated with atypical antipsychotics. International Clinical Psychopharmacology, 17(4), 145-160. https://doi.org/10.1097/00004850-200207000-00001
22. Lee, K., Abraham, S., & Cleaver, R. (2022). A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis. General Hospital Psychiatry, 78, 58-67. https://doi.org/10.1016/j.genhosppsych.2022.07.006
23. Maccora, C., Ciuoli, C., Goracci, A., Benenati, N., Formichi, C., Pilli, T., ... & Castagna, M. G. (2020). One month weight loss predicts the efficacy of liraglutide in obese patients: data from a single center. Endocrine Practice, 26(2), 235-240. https://doi.org/10.4158/ep-2019-0169
24. Prasad, F., Agarwal, M., Hahn, M., & Mueller, D. J. (2022). P177. Semaglutide to the rescue: real-world clinical data in patients with antipsychotic-induced weight gain not responding to metformin. Biological Psychiatry, 91(9), S158-S159. https://doi.org/10.1177/20451253231165169
25. Tham, M., Chong, T. W., Jenkins, Z. M., & Castle, D. J. (2021). The use of anti-obesity medications in people with mental illness as an adjunct to lifestyle interventions—effectiveness, tolerability and impact on eating behaviours: a 52-week observational study. Obesity Research & Clinical Practice, 15(1), 49-57. https://doi.org/10.1016/j.orcp.2020.11.002
26. Citrome, L., Kalsekar, I., Baker, R. A., & Hebden, T. (2014). A review of real-world data on the effects of aripiprazole on weight and metabolic outcomes in adults. Current medical research and opinion, 30(8), 1629-1641. https://doi.org/10.1185/03007995.2014.908280
27. De Hert, M., Eramo, A., Landsberg, W., Kostic, D., Tsai, L. F., & Baker, R. A. (2015). Efficacy and safety of aripiprazole once-monthly in obese and nonobese patients with schizophrenia: a post hoc analysis. Neuropsychiatric disease and treatment, 1299-1306. https://doi.org/10.2147/ndt.s80479
28. Henderson, D. C., Fan, X., Copeland, P. M., Sharma, B., Borba, C. P., Boxill, R., ... & Goff, D. C. (2009). Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients. Journal of clinical psychopharmacology, 29(2), 165-169. https://doi.org/10.1097/jcp.0b013e31819a8dbe
29. Verma, A., Ranjan, R., Kumar, P., & Maharshi, V. (2026). Effect of Cariprazine versus Aripiprazole on Cardiometabolic Profile in Patients with Schizophrenia switched from Olanzapine due to Weight gain: A Randomized Controlled Trial. Journal of Psychiatric Research. https://doi.org/10.1016/j.jpsychires.2026.02.037
30. Halaris, A., & Wuest, J. (2019). Metabolic syndrome reversal with cariprazine. Journal of Clinical Psychopharmacology, 39(4), 413-416. https://doi.org/10.1097/jcp.0000000000001074
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Copyright (c) 2026 Krzysztof Brzezicki, Katarzyna Jolanta Kuc, Katarzyna Zegadło, Maciej Dobrucki, Mateusz Cieciora, Małgorzata Kawiorska, Julia Surowiec, Aleksandra Cieciora, Patryk Jakubiak, Wiktoria Ruta Bełcikowska-Skowron
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