In a clinical trial emulation study, researchers found small differences in mean weight change among eight first-line antidepressants; bupropion consistently showed the least weight gain, but medication adherence during follow-up was low.1,2
“Patients and their doctors often have several options when they first start taking an antidepressant. This study provides important real-world evidence about how much weight gain to expect after starting some of the most common antidepressants,” said Joshua Petimar, senior author of the study and an adjunct professor of population medicine at the Harvard Pilgrim Health Care Institute. “Doctors and patients can use this information, among other factors, to help decide which option is right for them.”3
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Researchers at Harvard Medical School and the Harvard Pilgrim Health Care Institute studied electronic medical records of more than 183,000 adults who initiated treatment with one of eight first-line antidepressants to assess medication-associated weight changes at 6, 12, and 24 months after participants began taking the medication. The eight medications studied were (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 on. The researchers then estimated the population-level effects of starting 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 after initiation. They then used inverse probability weighting from repeated outcome marginal structural models to account for baseline confounders and the informativeness of the outcome measures. The effects of starting and adhering to each treatment protocol were estimated in secondary analyses.
The researchers found differences in drug-induced weight gain both within and between antidepressant subclasses. Compared with sertraline, the estimated weight gain at 6 months was greater for escitalopram (difference of 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 initial weight than sertraline users. Fluoxetine use was not associated with weight change at 6 months compared with sertraline use. Escitalopram, paroxetine, and duloxetine were associated with a 10% to 15% higher risk of gaining at least 5% of initial weight. When the effects of baseline and adherence were estimated, the associations were stronger but had wider confidence intervals. Adherence at 6 months ranged from 28% (duloxetine) to 41% (bupropion). The study is published in Annals of Internal Medicine.1
“While there are a number of reasons why patients and their doctors may choose one antidepressant over another, weight gain is a major side effect that often leads patients to stop taking their medication,” said Jason Block, senior author of the study, a physician in general internal medicine and associate professor of population medicine at Harvard Pilgrim Health Care Institute. “Our study found that some antidepressants, such as bupropion, are associated with less weight gain than others. Patients and their doctors might consider weight gain as a reason to choose a medication that better fits their needs.”3
Because weight gain may affect adherence to drug therapy, physicians should consider potential weight gain when initiating antidepressant therapy with patients.
References
1. Petimar J, Young JG, Yu H, et al. Drug-induced weight change in common antidepressant treatments: a clinical trial emulation study. Ana Medical InternJuly 2, 2024. Online ahead of print.
2. Choice of medication may affect weight gain when starting antidepressant treatment. American College of Physicians. Press release. July 1, 2024. Accessed July 3, 2024. https://www.eurekalert.org/news-releases/1049459
3. Weight change as a function of common antidepressant medications. Harvard Pilgrim Health Care Institute. Press release. July 1, 2024. Accessed July 3, 2024. https://www.eurekalert.org/noticias/1049472
