• Joshua Petimar, Jessica G Young, Han Yu, Sheryl L Rifas-Shiman, Matthew F Daley, William J Heerman, David M Janicke, W Schuyler Jones, Kristina H Lewis, Pi-I D Lin, Carly Prentice, John W Merriman, Sengwee Toh, and Jason P Block.
• Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (J.P., J.G.Y.).
• Ann. Intern. Med. 2024 Aug 1; 177 (8): 9931003993-1003.

BackgroundAntidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited.ObjectiveTo compare weight change across common first-line antidepressant treatments by emulating a target trial.DesignObservational cohort study over 24 months.SettingElectronic health record (EHR) data from 2010 to 2019 across 8 U.S. health systems.Participants183 118 patients.MeasurementsPrescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine. The investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation. Inverse probability weighting of repeated outcome marginal structural models was used to account for baseline confounding and informative outcome measurement. In secondary analyses, the effects of initiating and adhering to each treatment protocol were estimated.ResultsCompared with that for sertraline, estimated 6-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31 to 0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20 to 0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22 to 0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03 to 0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02 to 0.23 kg]); similar for fluoxetine (difference, -0.07 kg [CI, -0.19 to 0.04 kg]); and lower for bupropion (difference, -0.22 kg [CI, -0.33 to -0.12 kg]). Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion).LimitationNo data on medication dispensing, low medication adherence, incomplete data on adherence, and incomplete data on weight measures across time points.ConclusionSmall differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low. Clinicians could consider potential weight gain when initiating antidepressant treatment.Primary Funding SourceNational Institutes of Health.

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