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Antidepressants and Body Weight: A Comprehensive Review and Meta-Analysis
Abstract
OBJECTIVE: Psychotropic drugs often induce weight gain, leading to discomfort and discontinuation of treatment and, more importantly, increasing the risk of obesity-related illnesses such as diabetes mellitus, hypertension, and coronary heart disease. There is evidence that antidepressant drugs may induce a variable amount of weight gain, but results are sparse and often contradictory. DATA SOURCES: We performed a literature search using the MEDLINE, ISI Web of Knowledge, and Cochrane research databases for all publications available to January 2009. We used the following keywords: antidepressant, psychotropic drugs, body weight, weight gain, obesity, overweight, adverse event, side effects, SSRIs, tricyclic antidepressants, and the name of each antidepressant active compound together with body weight or other keywords. Studies reporting body weight changes during treatment with different antidepressants were selected for eligibility. Finally, 116 studies were included in the analysis. DATA EXTRACTION: Weight change mean and standard deviation and size of each group were recorded. Missing means and standard deviations were directly calculated by using information available in the article when possible. Non-placebo-controlled studies were compared to a virtual placebo sample, whose mean and standard deviation were derived by the weighted mean of means and standard deviations of all placebo samples. Methodological quality of studies, heterogeneity, publication bias, and effect of treatment duration were systematically controlled. DATA SYNTHESIS: Quantitative results evidenced that amitriptyline, mirtazapine, and paroxetine were associated with a greater risk of weight gain. In contrast, some weight loss occurs with fluoxetine and bupropion, although the effect of fluoxetine appears to be limited to the acute phase of treatment. Other compounds have no transient or negligible effect on body weight in the short term. However, the effect of each antidepressant may vary greatly depending on an individual's characteristics and generally became more evident in the long term to a variable degree across compounds. CONCLUSIONS: Despite the fact that some analyses were done on only a few studies due to the difficulty of finding reliable information in literature, to our knowledge, this is the first comprehensive meta-analysis to allow comparison of different antidepressants as regards their impact on body weight. Data presented may be helpful for a more accurate treatment selection in patients at risk of obesity or related medical illness.
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“the persistence of some residual symptoms (e.g., cognitive and sleep disturbances)”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [5]
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“The sedative antidepressants may also induce a weight gain, what is particularly shown for mirtazapine but not for trazodone [23].”
From Effects of Antidepressants on Sleep (2017) · cites this paper as [23]
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“Amitriptyline and mirtazapine consistently showed weight gaining effects throughout acute and long-term treatment.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [70]
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“A meta-analysis further showed that SSRIs including citalopram, escitalopram, fluoxetine, sertraline, paroxetine and SNRIs including venlafaxine and duloxetine were associated with weight loss compared with placebo.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [70]
In the citing paper
“Imipramine and bupropion showed significant weight loss effects for both acute and long term treatment (Table 5).70”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [70]
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BackgroundDepression therapy for somatic diseases
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Kautzky, A., Heneis, K., Stengg, K., Fröhlich, S., & Kautzky‐Willer, A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111096 · Cited by 6
“CR findings in mental health are promising as most psychopharmacological agents bear a risk of weight gain and potentially deflect glucose metabolism to diabetogenic states [61].”
BackgroundRanjan, P., Vikram, N. K., Kumari, A., Chopra, S., Choranur, A., Pradeep, Y., Puri, M., Malhotra, A., Ahuja, M., Meeta, et al. (2022) · Journal of Family Medicine and Primary Care · doi:10.4103/jfmpc.jfmpc_51_22 · Cited by 5
“Among the antidepressants, amitriptyline, mirtazapine, and paroxetine are associated with greater weight gain as compared to other medications.[132] Similarly, antipsychotics are associated with weight gain, with clozapine and olanzapine being associated with the highest risk of weight gain.”
BackgroundFluoxetine for adult overweight or obese people
Meléndez, G., Serralde-Zúñiga, A. E., Garay, A. G. G., Rodríguez‐Carmona, Y., & Galicia, C. S. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011688 · Cited by 5
Cardiometabolic Risk and Monitoring in Psychiatric Disorders
Samaras, K. (2016) · Springer eBooks · doi:10.1007/978-3-319-32480-7_18 · Cited by 5
Mendoza, K. A., Stockinger, D. E., Cukrov, M., Roberts, J. A., & Hwa, G. G. C. (2021) · Journal of Medical Primatology · doi:10.1111/jmp.12512 · Cited by 5
Hannoodee, H., Khalili, M. A., Theik, N. W. Y., Raji, O. E., Shenwai, P., Shah, R., Kalluri, S. R., Bhutta, T. H., & Khan, S. (2021) · Cureus · doi:10.7759/cureus.16998 · Cited by 5
“Thus, place patients on those medications are at an increased risk of ACS and its complication including all-cause bleeding, death, and stroke [35-41].”
BackgroundSymptom networks in major depressive disorder and treatment response: special focus on TRD
Kautzky, A., Bartova, L., Dold, M., Souery, D., Montgomery, S., Zohar, J., Mendlewicz, J., Fabbri, C., Serretti, A., Tretiakov, E. O., et al. (2025) · European Psychiatry · doi:10.1192/j.eurpsy.2025.2454 · Cited by 6
“However, decreased appetite can be easily targeted by treatment, and response in this symptom domain was more easily predictable by machine learning classification models than other symptoms such as emotional or anxious symptoms [14, 46].”
Self-citationGut microbiome and glial cell dialog: Role of TCM in the treatment of depression
Zhang, X., Chen, X., Ruan, S., Wang, H., Xu, Y., Fu, H., Lin, S., Efferth, T., Tian, Y., Li, C., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157196 · Cited by 4
Treviño‐Alvarez, A. M., Gluck, M. E., McElroy, S. L., & Barboza, A. B. C. (2024) · Brain Sciences · doi:10.3390/brainsci14080841 · Cited by 4
“Fluoxetine and bupropion were associated with weight loss, while other antidepressants had no significant effect on body weight [51].”
BackgroundPharmakotherapie der Essstörungen—Ein Update
Bauman, T., & Voderholzer, U. (2025) · Der Nervenarzt · doi:10.1007/s00115-025-01804-y · Cited by 4
Casanova, F., O’Loughlin, J., Lewis, C. M., Frayling, T. M., Wood, A. R., & Tyrrell, J. (2022) · International Journal of Epidemiology · doi:10.1093/ije/dyac052 · Cited by 4
“An antidepressant–obesity interaction, if real, would fit with previous studies highlighting weight gain during antidepressant treatment.(9,10) Several BMI variants demonstrated a nominal interaction with MD, with all variants demonstrating a stronger effect on BMI in people with depression.”
BackgroundResultZurchimitten, G., Camerini, L., Izídio, G. S., & Ghisleni, G. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111154 · Cited by 4
Prise en charge des troubles du comportement alimentaire dans la schizophrénie
Kouidrat, Y., Amad, A., Renard, N., Corneille, F., Lalau, J., & Loas, G. (2016) · Soins Psychiatrie · doi:10.1016/j.spsy.2015.04.011 · Cited by 4
Mel, V. N. D., Korman, N., McArdle, P., et al. (2018) · Australasian Psychiatry · doi:10.1177/1039856218772253 · Cited by 4
Leveraging Population‐Based Clinical Quantitative Phenotyping for Drug Repositioning
Brown, A. S., Rasooly, D., & Patel, C. J. (2017) · CPT Pharmacometrics & Systems Pharmacology · doi:10.1002/psp4.12258 · Cited by 4
“Using the normoglycemic cohort, we performed comprehensive association testing between prescription drug use and either fasting blood glucose or blood glucose following an oral glucose tolerance test, adjusting for age, sex, race, and BMI.”
MethodPrecision medicine in mood disorders
Serretti, A. (2022) · Psychiatry and Clinical Neurosciences Reports · doi:10.1002/pcn5.1 · Cited by 4
“14 Following the findings of those studies, and others available in literature, it is possible to implement a precision medicine strategy that is based on clinical information.”
BackgroundSelf-citationGutiérrez, L., Pérez, A. M. L., Catalá, P., Écija, C., Collado‐Mateo, D., Gil-Arias, A., & Peñacoba, C. (2023) · Applied Sciences · doi:10.3390/app13021191 · Cited by 4
Hühne-Landgraf, A., Laurent, K., Frisch, M. K., Wehr, M. C., Rossner, M. J., & Landgraf, D. (2023) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2023.06.002 · Cited by 4
“…of disorders usually imposes a severe burden on affected individuals and often presents challenges to therapists treating both conditions; for example, psychotropic drugs often have metabolic side effects and can only be used with caution in the presence of preexisting metabolic conditions (3,4).”
BackgroundKozela, M., Stepaniak, U., Koziara, K., Karpińska, I. A., Major, P., & Matyja, M. (2024) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-024-01645-9 · Cited by 4
“This observation is inconsistent with the results of studies that indicate body weight gain as an adverse effect of mental disorders treat-ment [26–29].”
BackgroundResultRautio, N., Jokelainen, J. J., Oksa, H. H., Saaristo, T., Moilanen, L., Vanhala, M. J., Peltonen, M., Korpi-Hyövälti, E., Tuomilehto, J. O., Uusitupa, M. I. J., et al. (2013) · Primary care diabetes · doi:10.1016/j.pcd.2013.10.005 · Cited by 4
“[26] A.”
BackgroundLong-term antidepressant treatment in general practice: changes in body mass index
Chiwanda, L., Cordiner, M., Thompson, A. T., et al. (2016) · BJPsych Bulletin · doi:10.1192/pb.bp.115.052472 · Cited by 4
de Bruin, I. J. A., Klop, C., Wyers, C. E., Overbeek, J. A., Geusens, P., van den Bergh, J. P., Driessen, J. H. M., & de Vries, F. (2019) · Osteoporosis International · doi:10.1007/s00198-019-04851-9 · Cited by 4
Liu, Y.-T., Chau, Y., Hsu, S., Chu, C., & Chen, C.-Y. (2012) · Asia-Pacific Psychiatry · doi:10.1111/j.1758-5872.2012.00223.x · Cited by 4
“Unfortunately, most antipsychotics and mood stabilizers are associated with weight gain and increase the risk of obesity in psychiatric patients (Chengappa et al., 2002; Leucht et al., 2009; Nasrallah, 2003; Serretti and Mandelli, 2010).”
BackgroundAffections métaboliques et psychiatrie
Duval, F. (2013) · Encyclopédie médico-chirurgicale. Psychiatrie · doi:10.1016/s0246-1072(13)60022-x · Cited by 4
Psychopharmakotherapie bei Herz-Kreislauf-Erkrankungen
Cordes, J., Lange‐Asschenfeldt, C., Hiemke, C., & Kahl, K. G. (2012) · Der Internist · doi:10.1007/s00108-012-3070-1 · Cited by 4
Fuller, M. A. (2016) · Springer eBooks · doi:10.1007/978-1-4939-2528-5_34 · Cited by 4
Metadata
- Authors
- Serretti, A., & Mandelli, L.
- Affiliations
- University of Bologna (IT)
- Corresponding author
- Serretti, Alessandro
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2010-10-15
- Volume
- 71
- Issue
- 10
- Pages
- 1259-1272
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2030270520
- Cited by
- 621
- References
- 0
- Citations by year
- 2026: 40 · 2025: 44 · 2024: 46 · 2023: 41 · 2022: 42 · 2021: 41 · 2020: 33 · 2019: 36 · 2018: 37 · 2017: 36 · 2016: 31 · 2015: 47 · 2014: 40 · 2013: 49 · 2012: 41
- FWCI
- 25.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- antidepressants, weight gain, body weight, psychotropic drugs, obesity, amitriptyline, mirtazapine, paroxetine, fluoxetine, bupropion, tricyclic antidepressants, selective serotonin reuptake inhibitors, adverse drug reactions, treatment discontinuation
- MeSH terms
- Antidepressive Agents, Body Weight, Clinical Trials as Topic, Humans, Time Factors, Weight Gain, Weight Loss
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