Which Antidepressant Causes the Least Amount of Weight Gain?

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New research found that among 8 first-line antidepressants, bupropion was associated with the least weight gain most consistently.

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In a target trial emulations study, investigators found small differences in mean weight change between 8 first-line antidepressants; bupropion consistently showed the least weight gain, but medication adherence over follow-up was low.1,2

“Patients and their clinicians often have several options when starting an antidepressant for the first time. This study provides important real-world evidence regarding the amount of weight gain that should be expected after starting some of the most common antidepressants,” said Joshua Petimar, lead author of the study and assistant professor of population medicine at the Harvard Pilgrim Health Care Institute. “Clinicians and patients can use this information, among other factors, to help decide on the right choice for them.”3

Investigators from Harvard Medical School and Harvard Pilgrim Health Care Institute studied electronic health records for more than 183,000 adult individuals who initiated treatment with 1 of 8 first-line antidepressants to assess changes in weight by medication at 6, 12, and 24 months after participants started taking it. The 8 medications studied included (1) sertraline, (2) citalopram, (3) bupropion, (4) escitalopram, (5) fluoxetine, (6) venlafaxine, (7) paroxetine, and (8) duloxetine. Participants’ prescription data determined which antidepressant they were initiated with. The investigators then estimated the population-level effects of initiating each treatment, relative to sertraline, on both mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months following initiation. They then used inverse probability weighting of repeated outcome marginal structural models to account for baseline confounding and informative outcome measurement. The effects of initiating and adhering to each treatment protocol were estimated in secondary analyses.

The investigators found differences in medication-induced weight gain both within and between antidepressant subclasses. When compared with 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]). Bupropion users gained 0.22 kg less weight and were 15% less likely to gain at least 5% of their baseline weight than sertraline users. Fluoxetine use was not associated with 6-month weight change compared with sertraline use. Escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight. When the effects of initiation and adherence were estimated, associations were stronger but had wider CIs. The 6-month adherence ranged from 28% (duloxetine) to 41% (bupropion). The study is published in Annals of Internal Medicine.1

“Although there are several reasons why patients and their clinicians might choose 1 antidepressant over another, weight gain is an important side effect that often leads to patients stopping their medication,” said Jason Block, senior author of the study, general internal medicine physician, and associate professor of population medicine at the Harvard Pilgrim Health Care Institute. “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.”3

As weight gain may impact medication adherence, clinicians should consider potential weight gain when initiating patients on antidepressant treatment.

References

1. 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 Jul 2. Online ahead of print.

2. Medication choice may affect weight gain when initiating antidepressant treatment. American College of Physicians. News release. July 1, 2024. Accessed July 3, 2024. https://www.eurekalert.org/news-releases/1049459

3. Weight change across common antidepressant medications. Harvard Pilgrim Health Care Institute. News release. July 1, 2024. Accessed July 3, 2024. https://www.eurekalert.org/news-releases/1049472

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