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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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Risk of specific cardiovascular diseases in obsessive-compulsive disorder
Isomura, K., Sidorchuk, A., Brander, G., Jernberg, T., Rück, A., Song, H., Valdimarsdóttir, U. A., Lichtenstein, P., Larsson, H., Rück, C., et al. (2020) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2020.12.066 · Cited by 34
The Nexus Between Diabetes and Depression: A Narrative Review
Habib, S., Sangaraju, S. L., Yepez, D., Grandes, X. A., & Manjunatha, R. T. (2022) · Cureus · doi:10.7759/cureus.25611 · Cited by 42
“In contrast, some weight loss was noticed with fluoxetine and bupropion [92].”
BackgroundSafety Considerations in Drug Treatment of Depression in HIV-Positive Patients
Watkins, C. C., Pieper, A. A., & Treisman, G. J. (2011) · Drug Safety · doi:10.2165/11592070-000000000-00000 · Cited by 33
Wong, B. C., Chau, C. K., Ao, F., Mo, C., Wong, S., Wong, Y. H., & So, H. (2018) · Depression and Anxiety · doi:10.1002/da.22861 · Cited by 30
Rindler, G. A., Gries, A., & Freidl, W. (2023) · Frontiers in Public Health · doi:10.3389/fpubh.2023.1206283 · Cited by 38
“Following the suggestions from an early review conducted by Fava, older antidepressants such as mirtazapine, within the subgroup of tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), may more frequently increase body weight compared to the newer generation of selective serotonin reuptake inhib…”
MethodDepression, its comorbidities and treatment, and childhood body mass index trajectories
Schwartz, B. S., Glass, T. A., Pollak, J., Hirsch, A. G., Bailey-Davis, L. D., Moran, T. H., & Bandeen‐Roche, K. (2016) · Obesity · doi:10.1002/oby.21627 · Cited by 31
“Some antidepressants have been associated with weight gain, especially in adults (13), and others with weight loss, with different propensities by medication classes.”
BackgroundPsychiatric Medication Use and Weight Outcomes One Year After Bariatric Surgery
Hawkins, M., Leung, S., Lee, A. H., Wnuk, S., Cassin, S. E., Hawa, R., & Sockalingam, S. (2019) · Psychosomatics · doi:10.1016/j.psym.2019.10.009 · Cited by 31
Schneider, M., Pauwels, P., Toto, S., Bleich, S., Grohmann, R., Heinze, M., & Greiner, T. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.05.001 · Cited by 31
Treatment of insomnia – effect of trazodone and hypnotics on sleep
Wichniak, A., Wierzbicka, A. E., & Jarema, M. (2021) · Psychiatria Polska · doi:10.12740/pp/125650 · Cited by 32
Impact of Antiseizure Medications on Appetite and Weight in Children
Buraniqi, E., Dabaja, H., & Wirrell, E. C. (2022) · Pediatric Drugs · doi:10.1007/s40272-022-00505-2 · Cited by 33
“Medications may also impact weight, with certain types of medication, such as tricyclic antidepressants or mirtazapine, more commonly associated with weight gain [19].”
BackgroundRóg, J., Wingralek, Z. J., Nowak, K., Grudzień, M., Grunwald, A., Banaszek, A., & Karakuła‐Juchnowicz, H. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13102819 · Cited by 31
“The KD leads to improved carbohydrate and lipid metabolism, which may inhibit the metabolic disturbances that may occur with many antidepressants and antipsychotic medications [15,30].”
BackgroundSolmi, M., Miola, A., Capone, F., Pallottino, S., Højlund, M., Firth, J., Siskind, D. J., Holt, R. I. G., Corbeil, O., Cortese, S., et al. (2024) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2024.2396396 · Cited by 35
“Despite their efficacy in treating SMIs, weight gain frequently occurs with antidepressants and especially antipsychotics [73,74], which not only contributes to obesity and CVD, but may also lead to medication nonadherence [49,73,75,76].”
The Interconnected Complexity of Diabetes and Depression
Beverly, E. A., & Gonzalez, J. S. (2025) · Diabetes Spectrum · doi:10.2337/dsi24-0014 · Cited by 36
“Overtreat-ment with antidepressants in people with diabetes can lead to a range of issues, including weight gain (93), hypoglycemia (94,95) and/or hyperglycemia (95), increased health care costs (96), medication burden (97), and polypharmacy (98).”
Long, N. E. D., Hyslop, J. R., Raha, S., Hardy, D. B., & Holloway, A. C. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.04.063 · Cited by 34
“It has been suggested that the increased risk of diabetes in patients taking SSRIs is related to drug-induced weight gain (Serretti and Mandelli, 2010) given that obesity is a significant risk factor for the development of T2D.”
BackgroundDandjinou, M., Sheehy, O., & Bérard, A. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-025908 · Cited by 31
“ADs have several side effects and some of them increase weight.(13) There is mounting evidence suggesting that AD classes might be involved in different ways in biological mechanisms such as weight gain, insulin resistance and glucose metabolism dysregulation to induce diabetes.”
BackgroundTsai, H.-P., Hou, P., Mao, F. C., Chang, C., Yang, W., Wu, C., Liao, H.-J., Lin, T.-C., Chou, L.-S., Hsiao, L., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22010409 · Cited by 31
“A conflicting report demonstrated an association of using a selective serotonin transporter inhibitor to enhance serotonin activity with weight loss; however, the effects were short lived, with a return to the original weight during the maintenance period [45].”
BackgroundCariprazine specificity profile in the treatment of acute schizophrenia
Corponi, F., Serretti, A., Montgomery, S., & Fabbri, C. (2017) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000189 · Cited by 30
“When SD of the mean was not available for continuous outcomes in the included studies, it was derived as described previously (Serretti and Mandelli, 2010).”
Self-citationTelo, G., Fontoura, L. F., Avila, G. O., Gheno, V., Brum, M. A. B., Teixeira, J., Erthal, I. N., Alessi, J., & Teló, G. (2024) · Obesity Reviews · doi:10.1111/obr.13696 · Cited by 29
“40 Moreover, pharmacological treatment employed in the management of diabetes, such as insulin, insulin secretagogues, or thiazolidinedione; and of epilepsy, such as antiepileptic drugs that include valproate, carbamaze-pine, and gabapentin, also increase the risk of weight gain.”
BackgroundPortman, D. J., Kaunitz, A. M., Kazempour, K., Mekonnen, H., Bhaskar, S., & Lippman, J. S. (2014) · Menopause The Journal of The North American Menopause Society · doi:10.1097/gme.0000000000000210 · Cited by 33
“appetite and food intake, and increases in body weight during the treatment of psychiatric disorders are common.(23,24) Many psychiatric medications, including SSRIs and SNRIs, can also adversely affect normal sexual response, probably by diminishing the function of the excitatory neurotransmitters dopamine and norepi…”
BackgroundSSRI or CRF antagonism partially ameliorate depressive-like behavior after adolescent social defeat
Bourke, C. H., Glasper, E. R., & Neigh, G. N. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.05.035 · Cited by 28
Fugger, G., Dold, M., Bartova, L., Kautzky, A., Souery, D., Mendlewicz, J., Serretti, A., Zohar, J., Montgomery, S., Frey, R., et al. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109638 · Cited by 30
Self-citationTreviño‐Alvarez, A. M., Sánchez-Ruiz, J. A., Barrera, F. J., Rodríguez-Bautista, M., Romo‐Nava, F., McElroy, S. L., & Barboza, A. B. C. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.03.050 · Cited by 28
Mötteli, S., Provaznikova, B., Vetter, S., Jäger, M., Seifritz, E., & Hotzy, F. (2023) · Nutrients · doi:10.3390/nu15092136 · Cited by 28
“However, despite a higher medication-induced risk for weight gain in the inpatients and the need to prevent metabolic side effects of psychiatric medication [6,7,9], BMI was significantly higher in the outpatients, which indicates the importance of lifestyle factors.”
BackgroundSelective Serotonin Reuptake Inhibitor Drug Interactions in Patients Receiving Statins
Andrade, C. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13f08941 · Cited by 28
Fluoxetine augments ventilatory CO2 sensitivity in Brown Norway but not Sprague Dawley rats
Hodges, M. R., Echert, A. E., Puissant, M. M., et al. (2013) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2013.02.020 · Cited by 27
Joseph, J., & Law, C. A. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.010 · Cited by 26
“Neuropsychiatric therapies are heterogeneous in their long-term efficacy (Geddes et al., 2000; McEvoy and Nathan, 2007; Serretti and Mandelli, 2010), with some having considerable harmful effects (Correll et al., 2009; De Hert et al., 2012; Lozano et al., 2008).”
Kukucka, T., Ferencová, N., Višňovcová, Z., Ondrejka, I., Hrtánek, I., Kovacova, V., Macejova, A., Mlyncekova, Z., & Tonhajzerová, I. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084511 · Cited by 30
“Several studies revealed that the severity of depressive symptoms does not seem to correlate well with drug-induced weight change [18].”
BackgroundCurcumin Reduces Depression in Obese Patients with Type 2 Diabetes: A Randomized Controlled Trial
Yaikwawong, M., Jansarikit, L., Jirawatnotai, S., & Chuengsamarn, S. (2024) · Nutrients · doi:10.3390/nu16152414 · Cited by 28
“Conventional antidepressants, while effective, can induce weight gain by affecting neurotransmitters such as serotonin and histamine, which regulate appetite and metabolism [53,54].”
BackgroundMiidera, H., Enomoto, M., Kitamura, S., Tachimori, H., & Mishima, K. (2020) · Diabetes Care · doi:10.2337/dc19-1175 · Cited by 25
An Updated Approach to Antiobesity Pharmacotherapy: Moving Beyond the 5% Weight Loss Goal
Enright, C., Thomas, E., & Saxon, D. R. (2023) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac195 · Cited by 27
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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