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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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“However, less evidence is available regarding the long-term impact of antidepressants on weight, and some associations appear to be transient (19-24).”
BackgroundEffects of novel antidepressant drugs on mesenchymal stem cell physiology
Ferroni, L., Gardin, C., Bellin, G., Vindigni, V., Pavan, C., & Zavan, B. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108853 · Cited by 14
“Fluoxetine is the most prescribed SSRI, as it is well tolerated by patients, it is not associated with weight gain, but with weight loss during the acute phase of treatment [7,8].”
BackgroundKochavi, B., Mendelowitsch, S., Enoch‐Levy, A., Yaroslavsky, A., Toledano, A., Modan‐Moses, D., & Stein, D. (2020) · International Journal of Eating Disorders · doi:10.1002/eat.23301 · Cited by 14
Lee, S. H., Mastronardi, C. A., Li, R. W., Paz-Filho, G., Dutcher, E. G., Lewis, M. D., Vincent, A. D., Smith, P. N., Bornstein, S. R., Licinio, J., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-018-0351-z · Cited by 12
Scala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 13
Self-citationPsychopharmacological Considerations for Gender-Affirming Hormone Therapy
Kim, H.-H., Goetz, T. G., Grieve, V. L. B., & Keuroghlian, A. S. (2023) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000373 · Cited by 15
Zeng, P., Jiang, C. S., Cao, J., Li, M., & Lin, F. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.07.080 · Cited by 13
Can botulinum toxin improve mood in depressed patients?
Han, C., Park, G., Wang, S., Lee, S.-Y., Lee, S.-J., Bahk, W., & Pae, C. (2012) · Expert Review of Neurotherapeutics · doi:10.1586/ern.12.92 · Cited by 12
Keenan, R. J., Chan, J., Donnelly, P. S., Barnham, K. J., & Jacobson, L. H. (2018) · Neurobiology of Stress · doi:10.1016/j.ynstr.2018.09.008 · Cited by 13
“A number of studies have associated antidepressant treatment such as fluoxetine with inhibition of weight gain in humans (Halford et al., 2007; Li et al., 2005; Michelson et al., 1999; Serretti and Mandelli, 2010) and in rodents (Grignaschi and Samanin,”
BackgroundPlaeke, P., Eede, F. V. D., Gys, B., Beunis, A., Ruppert, M., Man, J. D., Winter, B. Y. D., & Hubens, G. (2019) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-019-01784-z · Cited by 13
Zhang, J., Zhang, Z., Zhang, J., Zheng, Z., Yao, Z., Qu, S., & Huang, Y. (2019) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2019/3424698 · Cited by 13
“Paroxetine, SSRI used in this research, is associated with a greater risk of weight gain among antidepressants [39].”
Lin, C., Chung, C., Chen, L., Chien, W., & Chou, P. (2019) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.7910 · Cited by 13
La relación entre la obesidad y estados depresivos
Rodrigo Alonso, K., & Olivos, C. (2020) · Revista Médica Clínica Las Condes · doi:10.1016/j.rmclc.2020.02.004 · Cited by 15
The Potential Role of Serotonergic Hallucinogens in Depression Treatment
Psiuk, D., Nowak, E., Cholewa, K., Łopuszańska, U., & Samardakiewicz, M. (2021) · Life · doi:10.3390/life11080765 · Cited by 12
Chang, J. P., Iqbal, A. Z., Do, Q. L., Yaseen, M., Wu, S., Malau, I. A., Zailani, H., & Su, K. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107857 · Cited by 13
Levy, D. M., Arush, O. B., Carmi, L., Juven‐Wetzler, A., & Zohar, J. (2024) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2024.152486 · Cited by 15
Long, N. E. D., Hyslop, J. R., Nicholson, C. J., Morrison, K. M., Gerstein, H. C., & Holloway, A. C. (2013) · Reproductive Sciences · doi:10.1177/1933719113477493 · Cited by 12
“Postnatally, there was no effect of bupropion on food consumption or body weight in either the mothers or their offspring despite the fact that bupropion treatment has been reported to cause decreased food consumption in nonpregnant rats and result in weight loss in humans.(37,38) The lack of any effect of development…”
Prevalence and Factors Associated With Psychiatric Medication Use in Bariatric Surgery Candidates
Hawkins, M., Lee, A., Leung, S., Hawa, R., Wnuk, S., Yanofsky, R., & Sockalingam, S. (2018) · Psychosomatics · doi:10.1016/j.psym.2018.11.007 · Cited by 11
Chirokikh, A., Uddin, S. M. Z., Areikat, N., Jones, R., Duque, E., Connor, C., Hadjiargyrou, M., Thanos, P. K., & Komatsu, D. E. (2022) · Bone · doi:10.1016/j.bone.2022.116637 · Cited by 13
Senior, D., McCarthy, M., Ahmed, R., Klein, S., Lee, W. X., Hadjiargyrou, M., Komatsu, D. E., Steiner, H., & Thanos, P. K. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100127 · Cited by 12
“Combined use of MP and FLX has been shown to induce changes in body weight and behavior [10] as well as in gene regulation in the striatum that mimic effects of cocaine, and that have been previously associated with an increased risk for addictive-like behaviors [5].”
BackgroundRapid Weight Gain Associated With Edema After Use of Paroxetine and Venlafaxine
Uğuz, F. (2014) · Clinical Neuropharmacology · doi:10.1097/wnf.0000000000000012 · Cited by 12
“Systematic reviews reported that whereas paroxetine was related to a greater risk of weight gain compared to other antidepressants except amitriptyline and mirtazapine, venlafaxine had a minimal effect on weight gain.(2,3) The mechanisms of weight gain secondary to antidepressant medications are unclear.”
ResultAntidepressant Use and Glycemic Control in Diabetic Population: A Meta-analysis
Khapre, M. P., Kant, R., Sharma, D., & Sharma, A. (2020) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_258_20 · Cited by 12
Blampied, M., Tylianakis, J. M., Bell, C., Gilbert, C., & Rucklidge, J. J. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.05.077 · Cited by 11
Almazan, E., Schwartz, J. L., & Gudzune, K. A. (2023) · Clinical Obesity · doi:10.1111/cob.12609 · Cited by 12
Bozdağ, D., van Voorthuizen, J., Korpel, N. L., Lentz, S. B. I., Gürer-Orhan, H., & Kamstra, J. H. (2024) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2024.116937 · Cited by 12
Ovlyakulov, B., Hu, B., Kan, H.-Y., Guo, Q., Li, X., Fan, H.-H., Wu, H., Wang, J., Zhang, X., & Zhu, J. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112715 · Cited by 11
Shell, A. L., Williams, M. K., Patel, J. S., Vrany, E. A., Considine, R. V., Acton, A. J., & Stewart, J. C. (2022) · Journal of Behavioral Medicine · doi:10.1007/s10865-022-00356-9 · Cited by 11
“…person with depression and hyperphagia, it might be important to avoid antidepressants with weightincreasing effects (e.g., paroxetine and mirtazapine) and instead prescribe antidepressants with weight-decreasing effects (e.g., bupropion and fluoxetine; Domecq et al., 2015; Serretti et al., 2010).”
BackgroundMcIntyre, R. S., Fayyad, R. S., Guico‐Pabia, C. J., & Boucher, M. (2015) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.14m01741 · Cited by 11
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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