Effects of antidepressants on weight: mechanisms, clinical effects, and management strategies
- Authors: Bairamalov V.A.1, Dautova V.A.1, Bakhareva M.D.2, Zavgorodniaia- Mariams A.S.2, Alyeva L.R.3, Ismikhanov M.M.4, Gazizova A.I.5, Zorina N.A.6, Malinina Y.A.7, Vedernikova V.А.3, Melnik R.K.6, Malyar E.I.1, Shamsutdinova A.R.1, Kicheva B.M.4, Gulieva N.B.3
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Affiliations:
- Bashkir State Medical University
- I.P. Pavlov First St. Petersburg State Medical University
- Privolzhsky Research Medical University
- Rostov State Medical University
- Kazan State Medical University
- The First Sechenov Moscow State Medical University
- Voronezh State Medical University
- Issue: Vol 31, No 3 (2025)
- Pages: 250-262
- Section: Reviews
- Submitted: 01.03.2025
- Accepted: 09.04.2025
- Published: 11.06.2025
- URL: https://medjrf.com/0869-2106/article/view/675281
- DOI: https://doi.org/10.17816/medjrf675281
- EDN: https://elibrary.ru/ERPBGF
- ID: 675281
Cite item
Abstract
Depression and obesity are common conditions that significantly affect the quality of life and public health. In recent decades, depression has become more prevalent, resulting in increased use of antidepressants. Despite their proven efficacy, antidepressants have significant side effects. One of them is weight gain, which can exacerbate obesity and metabolic disorders.
The review discusses the underlying mechanisms of antidepressant effects on weight, including neurotransmitter, inflammatory, and genetic factors. The metabolic profiles of various antidepressant classes are evaluated, with a focus on selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, tricyclic antidepressants, and monoamine oxidase inhibitors. Available weight management strategies are presented, including treatment adjustment, behavioral interventions, pharmacological treatments, and bariatric surgery. The importance of personalized selection of antidepressants and complex management strategies for patients with depression and obesity is emphasized.
Full Text

About the authors
Vyacheslav A. Bairamalov
Bashkir State Medical University
Author for correspondence.
Email: chirach726@gmail.com
ORCID iD: 0009-0003-5626-1752
Russian Federation, Ufa
Vilena A. Dautova
Bashkir State Medical University
Email: vilench9@gmail.com
ORCID iD: 0009-0005-7211-4263
Russian Federation, Ufa
Maria D. Bakhareva
I.P. Pavlov First St. Petersburg State Medical University
Email: bakha.mashereva@gmail.com
ORCID iD: 0009-0005-3197-4769
Russian Federation, Saint Petersburg
Aleksandra S. Zavgorodniaia- Mariams
I.P. Pavlov First St. Petersburg State Medical University
Email: zavgar_m7686@mail.ru
ORCID iD: 0009-0005-4413-4750
Russian Federation, Saint Petersburg
Lala R. Alyeva
Privolzhsky Research Medical University
Email: lala.alyeva@bk.ru
ORCID iD: 0009-0000-5745-0764
Russian Federation, Nizhny Novgorod
Murad M. Ismikhanov
Rostov State Medical University
Email: ismikhanov.murad@bk.ru
ORCID iD: 0009-0007-2887-290X
Russian Federation, Rostov-on-Don
Alina I. Gazizova
Kazan State Medical University
Email: G.alina17@icloud.com
ORCID iD: 0009-0006-2427-9546
Russian Federation, Kazan
Nelly A. Zorina
The First Sechenov Moscow State Medical University
Email: zorinanelly@mail.ru
ORCID iD: 0009-0005-4017-1087
Russian Federation, Moscow
Yana A. Malinina
Voronezh State Medical University
Email: yanamalinin4@yandex.ru
ORCID iD: 0009-0004-3991-4165
Russian Federation, Voronezh
Vladislava А. Vedernikova
Privolzhsky Research Medical University
Email: vladavedernicova@gmail.com
ORCID iD: 0009-0008-4148-1310
Russian Federation, Nizhny Novgorod
Roman K. Melnik
The First Sechenov Moscow State Medical University
Email: romelnyk3@gmail.com
ORCID iD: 0009-0008-3319-6405
Russian Federation, Moscow
Elina I. Malyar
Bashkir State Medical University
Email: elinamalyar@yandex.ru
ORCID iD: 0009-0009-2181-092X
Russian Federation, Ufa
Aigiza R. Shamsutdinova
Bashkir State Medical University
Email: rimovna49@gmail.com
ORCID iD: 0009-0005-9849-2764
Russian Federation, Ufa
Bella M. Kicheva
Rostov State Medical University
Email: bellkicheva@mail.ru
ORCID iD: 0009-0000-0922-2521
Russian Federation, Rostov-on-Don
Narmin B. Gulieva
Privolzhsky Research Medical University
Email: narmin.gulieva28@mail.ru
ORCID iD: 0009-0009-1394-942X
Russian Federation, Nizhny Novgorod
References
- Perry C, Guillory TS, Dilks SS. Obesity and psychiatric disorders. Nurs Clin North Am. 2021;56(4):553–563. doi: 10.1016/j.cnur.2021.07.010 EDN: ZCATTK
- Balashova AV, Mamleeva DV, Machekhina LV, Dudinskaya EN. Metabolic adverse effects of antipsychotics: the state of the problem and management options. Obesity and Metabolism. 2022;19(4):431–441. doi: 10.14341/omet12935 EDN: WDPMME
- Ostroumova OD, Sapozhnikova YuI, Kochetkov AI, Starodubova AV. Drug-induced weight gain. The Journal of General Medicine. 2020;(2):16–24. doi: 10.24411/2071-5315-2020-12207 EDN: QBQFGD
- Gill H, Gill B, El-Halabi S, et al. Antidepressant medications and weight change: a narrative review. Obesity (Silver Spring). 2020;28(11):2064–2072. doi: 10.1002/oby.22969 EDN: YYPUYP
- Treviño-Alvarez AM, Sánchez-Ruiz JA, Barrera FJ, et al. Weight changes in adults with major depressive disorder: A systematic review and meta-analysis of prospective studies. J Affect Disord. 2023;332:1–8. doi: 10.1016/j.jad.2023.03.050 EDN: LOQXVU
- Piché ME, Tchernof A, Després JP. Obesity phenotypes, diabetes, and cardiovascular diseases. Circ Res. 2020;126(11):1477–1500. doi: 10.1161/CIRCRESAHA.120.316101
- Evstifeeva SE, Shalnova SA, Kutsenko VA, et al. Anxiety and depression: ten-year changes of prevalence and its association with demographic and socio-economic characteristics according to the ESSE-RF study. Cardiovascular Therapy and Prevention. 2023;22(S8):68–79. doi: 10.15829/1728-8800-2023-3796 EDN: ZRQCJG
- Bromet E, Andrade LH, Hwang I, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90. doi: 10.1186/1741-7015-9-90 EDN: XKKWUJ
- Brody DJ, Pratt LA, Hughes JP. Prevalence of depression among adults aged 20 and over: United States, 2013–2016. NCHS Data Brief. 2018;(303):1–8.
- Brody DJ, Gu Q. Antidepressant use among adults: United States, 2015–2018. NCHS Data Brief. 2020;(377):1–8.
- Lyubov EB, Vaskova LB, Tiapkina MV. Suicide rates and antidepressant utilization in Russia and its regions. Suicidology. 2017;27(2):49–53. EDN: ZAGQHP
- Damulin IV, Suvorova IA. The current concept of augmentation of treatment efficiency with antidepressant medication. S.S. Korsakov Journal of Neurology and Psychiatry. 2015;115(3):106–112. doi: 10.17116/jnevro201511531106-112 EDN: TVUJRX
- Sepúlveda-Lizcano L, Arenas-Villamizar VV, Jaimes-Duarte EB, et al. Metabolic adverse effects of psychotropic drug therapy: a systematic review. Eur J Investig Health Psychol Educ. 2023;13(8):1505–1520. doi: 10.3390/ejihpe13080110 EDN: EWIQUQ
- McIntyre RS, Kwan ATH, Rosenblat JD, et al. Psychotropic drug-related weight gain and its treatment. Am J Psychiatry. 2024;181(1):26–38. doi: 10.1176/appi.ajp.20230922 EDN: HXVVCG
- Simon MS, Barton BB, Glocker C, Musil R. A comprehensive approach to predicting weight gain and therapy response in psychopharmacologically treated major depressed patients: A cohort study protocol. PLoS One. 2022;17(7):e0271793. doi: 10.1371/journal.pone.0271793 EDN: QVKISC
- Kukucka T, Ferencova N, Visnovcova Z, et al. Mechanisms involved in the link between depression, antidepressant treatment, and associated weight change. Int J Mol Sci. 2024;25(8):4511. doi: 10.3390/ijms25084511 EDN: POZRJD
- Ricardo-Silgado ML, Singh S, Cifuentes L, et al. Association between CYP metabolizer phenotypes and selective serotonin reuptake inhibitors induced weight gain: a retrospective cohort study. BMC Med. 2022;20(1):261. doi: 10.1186/s12916-022-02433-x EDN: GMOWJE
- Anekwe CV, Ahn YJ, Bajaj SS, Stanford FC. Pharmacotherapy causing weight gain and metabolic alteration in those with obesity and obesity-related conditions: A review. Ann N Y Acad Sci. 2024;1533(1):145–155. doi: 10.1111/nyas.15112 EDN: LQXRIU
- Verhaegen AA, Van Gaal LF. Drugs affecting body weight, body fat distribution, and metabolic function-mechanisms and possible therapeutic or preventive measures: an update. Curr Obes Rep. 2021;10(1):1–13. doi: 10.1007/s13679-020-00419-5 EDN: SXUBAU
- El Asmar K, Annan NB, Khoury R, et al. Non-overweight depressed patients who respond to antidepressant treatment have a higher risk of later metabolic syndrome: findings from the METADAP cohort. Psychol Med. 2023;53(14):6560–6569. doi: 10.1017/S0033291722003919 EDN: DRMCXN
- Anagha K, Shihabudheen P, Uvais NA. Side effect profiles of selective serotonin reuptake inhibitors: a cross-sectional study in a naturalistic setting. Prim Care Companion CNS Disord. 2021;23(4):20m02747. doi: 10.4088/PCC.20m02747 EDN: DAQNZB
- Rachdi C, Damak R, Fekih Romdhane F, et al. Impact of sertraline on weight, waist circumference and glycemic control: A prospective clinical trial on depressive diabetic type 2 patients. Prim Care Diabetes. 2019;13(1):57–62. doi: 10.1016/j.pcd.2018.09.003
- Schneider M, Pauwels P, Toto S, et al. Severe weight gain as an adverse drug reaction of psychotropics: Data from the AMSP project between 2001 and 2016. Eur Neuropsychopharmacol. 2020;36:60–71. doi: 10.1016/j.euroneuro.2020.05.001 EDN: JTJBHN
- Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71(10):1259–1272. doi: 10.4088/JCP.09r05346blu
- Petimar J, Young JG, Yu H, et al. Medication-induced weight change across common antidepressant treatments: A Target Trial Emulation Study. Ann Intern Med. 2024;177(8):993–1003. doi: 10.7326/M23-2742 EDN: YRIXNM
- Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study. BMJ. 2018;361:k1951. doi: 10.1136/bmj.k1951 EDN: YGTLYT
- Poppen H, Oehlke K, Van Klompenburg E. Weight gain in veterans taking duloxetine, pregabalin, or both for the treatment of neuropathy. Fed Pract. 2021;38(5):238–242. doi: 10.12788/fp.0111 EDN: FBDYXR
- Kishi T, Ikuta T, Sakuma K, et al. Antidepressants for the treatment of adults with major depressive disorder in the maintenance phase: a systematic review and network meta-analysis. Mol Psychiatry. 2023;28(1):402–409. doi: 10.1038/s41380-022-01824-z EDN: MYKRTY
- Iosifescu DV, Jones A, O'Gorman C, et al. Efficacy and safety of AXS-05 (dextromethorphan-bupropion) in patients with major depressive disorder: a phase 3 randomized clinical trial (GEMINI). J Clin Psychiatry. 2022;83(4):21m14345. doi: 10.4088/JCP.21m14345 EDN: GZXZZP
- Walter TJ, Navarro M, Thiele TE, et al. A preliminary, open-label study of naltrexone and bupropion combination therapy for treating binge drinking in human subjects. Alcohol Alcohol. 2020;55(1):56–62. doi: 10.1093/alcalc/agz076
- Grilo CM, Lydecker JA, Morgan PT, Gueorguieva R. Naltrexone + bupropion combination for the treatment of binge-eating disorder with obesity: a randomized, controlled pilot study. Clin Ther. 2021;43(1):112–122.e1. doi: 10.1016/j.clinthera.2020.10.010 EDN: BBGZBL
- Grilo CM, Lydecker JA, Jastreboff AM, et al. Naltrexone/bupropion for binge-eating disorder: A randomized, double-blind, placebo-controlled trial. Obesity (Silver Spring). 2023;31(11):2762–2773. doi: 10.1002/oby.23898 EDN: WXUDXT
- Economos G, Lovell N, Johnston A, Higginson IJ. What is the evidence for mirtazapine in treating cancer-related symptomatology? A systematic review. Support Care Cancer. 2020;28(4):1597–1606. doi: 10.1007/s00520-019-05229-7 EDN: SDAQSG
- Cao J, Ouyang Q, Wang S, et al. Mirtazapine, a dopamine receptor inhibitor, as a secondary prophylactic for delayed nausea and vomiting following highly emetogenic chemotherapy: an open label, randomized, multicenter phase III trial. Invest New Drugs. 2020;38(2):507–514. doi: 10.1007/s10637-020-00903-8 EDN: RTFVPA
- Ulrich S, Ricken R, Buspavanich P, et al. Efficacy and adverse effects of tranylcypromine and tricyclic antidepressants in the treatment of depression: a systematic review and comprehensive meta-analysis. J Clin Psychopharmacol. 2020;40(1):63–74. doi: 10.1097/JCP.0000000000001153
- Luo Y, Kataoka Y, Ostinelli EG, et al. National prescription patterns of antidepressants in the treatment of adults with major depression in the US between 1996 and 2015: a population representative survey based analysis. Front Psychiatry. 2020;11:35. doi: 10.3389/fpsyt.2020.00035 EDN: IHUMSE
- Shyu BC, He AB, Yu YH, Huang ACW. Tricyclic antidepressants and selective serotonin reuptake inhibitors but not anticonvulsants ameliorate pain, anxiety, and depression symptoms in an animal model of central post-stroke pain. Mol Pain. 2021;17:17448069211063351. doi: 10.1177/17448069211063351 EDN: VOTQUK
- Danilov DS. A 70-year history of tricyclic antidepressants. S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(12):115–123. doi: 10.17116/jnevro2019119121115 EDN: RLSRZL
- Fiedorowicz JG, Brown L, Li J, et al. Obesogenic medications and weight gain over 24 weeks in patients with depression: results from the GUIDED study. Psychopharmacol Bull. 2021;51(4):8–30.
- Suchting R, Tirumalajaru V, Gareeb R, et al. Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: A systematic review and network meta-analysis. J Affect Disord. 2021;282:1153–1160. doi: 10.1016/j.jad.2021.01.021 EDN: ACOFHD
- Chamberlain SR, Baldwin DS. Monoamine oxidase inhibitors (MAOIs) in psychiatric practice: how to use them safely and effectively. CNS Drugs. 2021;35(7):703–716. doi: 10.1007/s40263-021-00832-x EDN: QDMKSB
- Edinoff AN, Swinford CR, Odisho AS, et al. Clinically relevant drug interactions with monoamine oxidase inhibitors. Health Psychol Res. 2022;10(4):39576. doi: 10.52965/001c.39576 EDN: ZMHFZI
- Ricken R, Ulrich S, Schlattmann P, Adli M. Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression. Eur Neuropsychopharmacol. 2017;27(8):714–731. doi: 10.1016/j.euroneuro.2017.04.003 EDN: BRFCWB
- Evans DL, Davidson J, Raft D. Early and late side effects of phenelzine. J Clin Psychopharmacol. 1982;2(3):208–210. doi: 10.1097/00004714-198206000-00007
- Epperson CN, Rubinow DR, Meltzer-Brody S, et al. Effect of Brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord. 2023;320:353–359. doi: 10.1016/j.jad.2022.09.143 EDN: RKRIPS
- Keam SJ. Gepirone extended-release: first approval. Drugs. 2023;83(18):1723–1728. doi: 10.1007/s40265-023-01975-5 EDN: BYLGCL
- Heo YA. Zuranolone: first approval. Drugs. 2023;83(16):1559–1567. doi: 10.1007/s40265-023-01953-x EDN: WEQVHS
- Clayton AH, Lasser R, Parikh SV, et al. Zuranolone for the treatment of adults with major depressive disorder: A Randomized, Placebo-Controlled Phase 3 Trial. Am J Psychiatry. 2023;180(9):676–684. doi: 10.1176/appi.ajp.20220459 EDN: BKJXSB
- Naguy A. Gepironethe latest antidepressant on market state-of-the-art or run-of-the-mill? Asian J Psychiatr. 2024;94:103937. doi: 10.1016/j.ajp.2024.103937 EDN: ASRVPR
- Bielski RJ, Cunningham L, Horrigan JP, et al. Gepirone extended-release in the treatment of adult outpatients with major depressive disorder: a double-blind, randomized, placebo-controlled, parallel-group study. J Clin Psychiatry. 2008;69(4):571–577. doi: 10.4088/jcp.v69n0408
- Keller MB, Ruwe FJ, Janssens CJ, et al. Relapse prevention with gepirone ER in outpatients with major depression. J Clin Psychopharmacol. 2005;25(1):79–84. doi: 10.1097/01.jcp.0000150221.53877.d9
- Montano CB, Jackson WC, Vanacore D, Weisler R. Considerations when selecting an antidepressant: a narrative review for primary care providers treating adults with depression. Postgrad Med. 2023;135(5):449–465. doi: 10.1080/00325481.2023.2189868 EDN: PIUCVQ
- Stogios N, Humber B, Agarwal SM, Hahn M. Antipsychotic-induced weight gain in severe mental illness: risk factors and special considerations. Curr Psychiatry Rep. 2023;25(11):707–721. doi: 10.1007/s11920-023-01458-0 EDN: HHBRVZ
- Pieters L, Blanken T, van Lunteren K, et al. A network model of health-related changes after a lifestyle-enhancing treatment in patients with severe mental illness: the MULTI Study VI. Int J Clin Health Psychol. 2024;24(1):100436. doi: 10.1016/j.ijchp.2024.100436 EDN: IGYJOW
- Finucane FM, Gibson I, Hughes R, et al. Factors associated with weight loss and health gains in a structured lifestyle modification programme for adults with severe obesity: a prospective cohort study. Front Endocrinol (Lausanne). 2023;14:1257061. doi: 10.3389/fendo.2023.1257061 EDN: ODGKYT
- Jerome GJ, Goldsholl S, Dalcin AT, et al. Comparing implementation strategies for an evidence-based weight management program delivered in community mental health programs: protocol for a pilot randomized controlled trial. JMIR Res Protoc. 2023;12:e45802. doi: 10.2196/45802 EDN: BBMMSL
- Speyer H, Jakobsen AS, Westergaard C, et al. Lifestyle interventions for weight management in people with serious mental illness: a systematic review with meta-analysis, trial sequential analysis, and meta-regression analysis exploring the mediators and moderators of treatment effects. Psychother Psychosom. 2019;88(6):350–362. doi: 10.1159/000502293
- Ojo O, Kalocsányiová E, McCrone P, et al. Non-pharmacological interventions for type 2 diabetes in people living with severe mental illness: results of a systematic review and meta-analysis. Int J Environ Res Public Health. 2024;21(4):423. doi: 10.3390/ijerph21040423 EDN: MJGIBP
- Grilo CM, Lydecker JA, Fineberg SK, et al. Naltrexone-bupropion and behavior therapy, alone and combined, for binge-eating disorder: randomized double-blind placebo-controlled trial. Am J Psychiatry. 2022;179(12):927–937. doi: 10.1176/appi.ajp.20220267 EDN: JEGODW
- Faulconbridge LF, Driscoll CFB, Hopkins CM, et al. Combined treatment for obesity and depression: a pilot study. Obesity (Silver Spring). 2018;26(7):1144–1152. doi: 10.1002/oby.22209
- Agarwal SM, Stogios N, Faulkner GEJ, Hahn M. Pharmacological interventions for the prevention of antipsychotic-induced weight gain in people with schizophrenia: a Cochrane systematic review and meta-analysis. Schizophr Bull. 2023;49(4):833–835. doi: 10.1093/schbul/sbad037 EDN: XPABDD
- Speyer H, Westergaard C, Albert N, et al. Reversibility of antipsychotic-induced weight gain: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:577919. doi: 10.3389/fendo.2021.577919 EDN: QMSBOL
- Lee K, Abraham S, Cleaver R. A systematic review of licensed weight-loss medications in treating antipsychotic-induced weight gain and obesity in schizophrenia and psychosis. Gen Hosp Psychiatry. 2022;78:58–67. doi: 10.1016/j.genhosppsych.2022.07.006 EDN: KAUATQ
- Sass MR, Danielsen AA, Köhler-Forsberg O, et al. Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (Sema Psychiatry). BMJ Open. 2023;13(1):e068652. doi: 10.1136/bmjopen-2022-068652 EDN: UFYVYG
- Lau D, Gamble JM. Suicidality among users of glucagon-like peptide-1 receptor agonists: An emerging signal? Diabetes Obes Metab. 2024;26(4):1150–1156. doi: 10.1111/dom.15459 EDN: XFQVJX
- Haugh S, Cromwell P, Kirrane R, Heneghan H. Impact of antidepressant use on post-operative weight loss following bariatric surgery. Ir J Med Sci. 2024;193(2):903–908. doi: 10.1007/s11845-023-03482-8 EDN: YGIZBH
- Jacobs A, Monpellier VM, Torensma B, et al. Influence of mental and behavioral factors on weight loss after bariatric surgery: A systematic review and meta-analysis. Obes Rev. 2024;25(6):e13729. doi: 10.1111/obr.13729 EDN: SRRVET
- Alyahya RA, Alnujaidi MA. Prevalence and outcomes of depression after bariatric surgery: a systematic review and meta-analysis. Cureus. 2022;14(6):e25651. doi: 10.7759/cureus.25651 EDN: NFDWJC
- Woods R, Moga AM, Ribeiro PAB, et al. Evolution of depressive symptoms from before to 24 months after bariatric surgery: A systematic review and meta-analysis. Obes Rev. 2023;24(5):e13557. doi: 10.1111/obr.13557 EDN: JWHHCI
- Hawkins M, Leung SE, Lee A, et al. Psychiatric medication use and weight outcomes one year after bariatric surgery. Psychosomatics. 2020;61(1):56–63. doi: 10.1016/j.psym.2019.10.009 EDN: GQOPON
- Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association Practice Guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868–872. doi: 10.1176/appi.ajp.2020.177901 EDN: SPIQJH
- Lv N, Kringle EA, Ma J. Integrated behavioral interventions for adults with comorbid obesity and depression: a systematic review. Curr Diab Rep. 2022;22(4):157–168. doi: 10.1007/s11892-022-01458-z EDN: LKQEPJ
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