Which first-line antidepressants cause the most weight gain?

Weight gain is a common side effect of antidepressants. It may lead to adverse effects on patients’ long-term metabolic health and lead some to stop taking their prescribed treatment. Although antidepressants overall are associated with weight gain, evidence on comparative weight change for specific first-line treatments is limited.1,2To examine this issue, U.S. researchers compared weight change across common first-line antidepressant treatments by emulating a randomized trial (i.e., by designing their ideal, hypothetical trial and aligning the data to match that trial as closely as possible). The observational cohort study used electronic health record data from 2010–2019 across eight U.S. health systems.1The investigators obtained prescription data for 183,118 adults who were new users of sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine or venlafaxine. They estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary endpoint) and the probability of gaining at least 5% of baseline weight (secondary endpoint) six months after initiation.1 The authors used inverse probability weighting to account for baseline confounding. The effects of initiating and adhering to each treatment protocol were estimated in secondary analyses.1Results showed the following:The most common antidepressant treatments initiated were sertraline (n=37,351 [20%]), citalopram (n=30,184 [16%]) and bupropion (n=27,054 [15%]). The least common was paroxetine (n=7,675 [4%]).Compared to sertraline, estimated six-month weight gain was higher for escitalopram (difference, 0.41 kg [95% CI, 0.31–0.52 kg]), paroxetine (difference, 0.37 kg [CI, 0.20–0.54 kg]), duloxetine (difference, 0.34 kg [CI, 0.22–0.44 kg]), venlafaxine (difference, 0.17 kg [CI, 0.03–0.31 kg]), and citalopram (difference, 0.12 kg [CI, 0.02–0.23 kg])Compared to sertraline, estimated six-month weight gain was similar for fluoxetine (difference, −0.07 kg [CI, −0.19–0.04 kg])Compared to sertraline, estimated six-month weight gain was lower for bupropion (difference, −0.22 kg [CI, −0.33 to −0.12 kg]). Escitalopram, paroxetine and duloxetine were associated with 10%–15% higher risk for gaining at least 5% of baseline weight.Bupropion was associated with a 15% reduced risk for gaining at least 5% of baseline weight. When the effects of initiation and adherence were estimated, weight change associations were stronger but had wider confidence intervals. Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion).The weight change results at 12- and 24-months were limited by low adherence rates, which were 16%–21% at 12 months, and only 4%–5% at 24 months.1The investigators concluded that their study found small differences in mean weight change among eight first-line antidepressants. Bupropion consistently showed the least weight gain, while escitalopram, paroxetine and duloxetine showed the most weight gain. Clinicians could consider potential weight gain when initiating antidepressant treatment, especially for patients with weight and metabolic health concerns.1In a press release accompanying the publication of the study data, senior author Jason Block, a general internal medicine physician and Harvard Medical School associate professor, commented that “Although there are several reasons why patients and their clinicians might choose one antidepressant over another, weight gain is an important side effect that often leads to patients stopping their medication. Our study found that some antidepressants, like bupropion, are associated with less weight gain than others. Patients and their clinicians could consider weight gain as one reason for choosing a medication that best fits their needs.”2 References:Petimar J, Young JG, Yu H, et al. Medication-induced weight change across common antidepressant treatments: a target trial emulation study. Ann Intern Med 2024; published online July 2, 2024. Harvard Pilgrim Health care Institute. Weight change across common antidepressant medications. News release July 1, 2024. (accessed July 3, 2024).

Which first-line antidepressants cause the most weight gain?

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