An Electronic Health Records Study of Long-Term Weight Gain Following Antidepressant Use
Open accessAbstract
IMPORTANCE: Short-term studies suggest antidepressants are associated with modest weight gain but little is known about longer-term effects and differences between individual medications in general clinical populations. OBJECTIVE: To estimate weight gain associated with specific antidepressants over the 12 months following initial prescription in a large and diverse clinical population. DESIGN, SETTING, AND PARTICIPANTS: We identified 22,610 adult patients who began receiving a medication of interest with available weight data in a large New England health care system, including 2 academic medical centers and affiliated outpatient primary and specialty care clinics. We used electronic health records to extract prescribing data and recorded weights for any patient with an index antidepressant prescription including amitriptyline hydrochloride, bupropion hydrochloride, citalopram hydrobromide, duloxetine hydrochloride, escitalopram oxalate, fluoxetine hydrochloride, mirtazapine, nortriptyline hydrochloride, paroxetine hydrochloride, venlafaxine hydrochloride, and sertraline hydrochloride. As measures of assay sensitivity, additional index prescriptions examined included the antiasthma medication albuterol sulfate and the antiobesity medications orlistat, phentermine hydrochloride, and sibutramine hydrochloride. Mixed-effects models were used to estimate rate of weight change over 12 months in comparison with the reference antidepressant, citalopram. MAIN OUTCOME AND MEASURE: Clinician-recorded weight at 3-month intervals up to 12 months. RESULTS: Compared with citalopram, in models adjusted for sociodemographic and clinical features, significantly decreased rate of weight gain was observed among individuals treated with bupropion (β [SE]: -0.063 [0.027]; P = .02), amitriptyline (β [SE]: -0.081 [0.025]; P = .001), and nortriptyline (β [SE]: -0.147 [0.034]; P < .001). As anticipated, differences were less pronounced among individuals discontinuing treatment prior to 12 months. CONCLUSIONS AND RELEVANCE: Antidepressants differ modestly in their propensity to contribute to weight gain. Short-term investigations may be insufficient to characterize and differentiate this risk.
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A more recent study using electronic health records included 22,610 patients with 19,244 patients prescribed an antidepressant for at least 3 months.
“The study included 22,610 patients with 19,244 patients prescribed an antidepressant for at least 3 months.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [71]
As controls, weight loss agents including orlistat, phentermine, and sibutramine all resulted in decrease in weight.
“As controls, they also included weight loss agents including orlistat, phentermine, and sibutramine, which all resulted in decrease in weight (Table 5).71”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [71]
All antidepressants caused weight gain rather than weight loss.
“All antidepressants caused weight gain rather than weight loss.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [71]
After adjusting for socio-demographic and clinical features, bupropion, amitriptyline, and nortriptyline caused significantly less weight gain than citalopram.
“After adjusting for socio-demographic and clinical features, bupropion, amitriptyline, and nortriptyline caused significantly less weight gain than citalopram.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [71]
Among patients who completed the study and had a weight measured at the 12-month point, in addition to the above three antidepressants, escitalopram also caused significantly less weight gain than citalopram.
“Among patients who completed the study and had a weight measured at the 12-month point, in addition to the above three antidepressants, escitalopram also caused significantly less weight gain than citalopram.”
From Addressing the Side Effects of Contemporary Antidepressant Drugs: A Comprehensive Review (2018) · cites this paper as [71]
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- Authors
- Blumenthal, S. R., Castro, V. M., Clements, C. C., Rosenfield, H. R., Murphy, S. N., Fava, M., Weilburg, J. B., Erb, J. L., Churchill, S. E., Kohane, I. S., Smoller, J. W., & Perlis, R. H.
- Affiliations
- Massachusetts General Hospital (US)
- Depression Clinic and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston
- Brigham and Women's Hospital (US)
- Information Systems, Partners HealthCare System, Boston, Massachusetts
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2014-08-01
- Volume
- 71
- Issue
- 8
- Pages
- 889
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC9980723
- OpenAlex
- W2025786817
- Cited by
- 151
- References
- 23
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 11 · 2023: 9 · 2022: 14 · 2021: 2 · 2020: 10 · 2019: 10 · 2018: 20 · 2017: 18 · 2016: 21 · 2015: 14 · 2014: 1
- FWCI
- 13.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Pfizer
- National Institutes of Health (R01NH100286)
- National Institute of Mental Health (R01MH100286)
- 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, long-term weight change, bupropion, amitriptyline, nortriptyline, duloxetine, citalopram, fluoxetine, paroxetine, sertraline, venlafaxine, mirtazapine, antidepressant side effects
- MeSH terms
- Adult, Amitriptyline, Antidepressive Agents, Tricyclic, Female, Humans, Male, Middle Aged, New England, Nortriptyline, Prospective Studies, Citalopram, Weight Gain, Body Mass Index, Bupropion, Antidepressive Agents, Second-Generation, Young Adult, Electronic Health Records
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