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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Standard antidepressants leave residual symptoms such as cognitive and sleep disturbances.
“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]
Amitriptyline and mirtazapine consistently showed weight gaining effects throughout acute and long-term treatment.
“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]
A meta-analysis showed that SSRIs including citalopram, escitalopram, fluoxetine, sertraline, paroxetine and SNRIs including venlafaxine and duloxetine were associated with weight loss compared with placebo.
“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]
Imipramine and bupropion showed significant weight loss effects for both acute and long term treatment.
“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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“Indeed, in addition to antipsychotics, patients often consume anxiolytics, antidepressants, and other mood stabilizers with well-documented side effects of increased appetite and weight gain [72].”
BackgroundWeight Considerations in Psychotropic Drug Prescribing and Switching
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“A meta-analysis 30 suggested that some antidepressants might cause weight change during long-term treatment.”
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“It’s those Pills that are Ruining Me”
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“Weight changes, especially weight gain, are unwanted side effects of many antidepressants and may contribute to co-morbidities and non-adherence to treatment regimens (Fava, 2000; Serretti and Mandelli, 2010).”
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The Impact of General Medical Conditions in Obsessive-Compulsive Disorder
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The interface of depression and diabetes: treatment considerations
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Musculoskeletal Pain, Fear Avoidance Behaviors, and Functional Decline in Obesity
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“Nortriptyline was associated with modest weight gain with acute (<12 weeks) use but not when used longer than 4 months.(110) Interestingly, a systematic review of adverse events associated with the use of antidepressants as a class found higher depression severity and 3 or more comorbid psychiatric diagnoses were asso…”
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“…increase in mean weight in study participants treated with vortioxetine during this study was comparable with that observed in the placebo group (0.8 kg) of a meta-analysis of long-term (> 8 months) placebo-controlled clinical studies that involved 12 antidepressants (Serretti and Mandelli, 2010).”
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“1 pISSN 1738-1088 / eISSN 2093-4327 Clinical Psychopharmacology and Neuroscience 2018;16(1):1-6 Copyrightc 2018, Korean College of Neuropsychopharmacology”
BackgroundSelf-citationVortioxetine (Lu AA21004) in the long-term open-label treatment of major depressive disorder
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Effect of caloric restriction on depression
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“Conversely, though other studies suggest that BDNF does not play an essential role in the regulation of energy expenditure [72], BDNF-deficient mice show hyperphagia and consequent obesity [73].”
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“antidepressants, the so-called selective serotonin reuptake inhibitors, have modest effects on body weight in short-term trials.(209,210) However, with long-term use of these drugs in general,”
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- 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 › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Pharmacology › 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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