Prescribed for a range of psychiatric conditions including depression, anxiety, chronic pain, and post-traumatic stress disorder, antidepressants have become the most frequently prescribed class of medications in the United States. The percentage of American adults using antidepressants rose from 11% in 2009-2010 to 14% in 2017-2018. While antidepressants rank among the most frequently prescribed drugs, data comparing weight fluctuations for primary treatment options remains scarce.

A study recently published in the Annals of Internal Medicine aimed to compare weight changes associated with eight common first-line antidepressant treatments using a target trial emulation approach. This comprehensive observational cohort study examined the association between common first-line antidepressant treatments and weight changes over time. Utilizing electronic health record (EHR) data from 2010 to 2019 across eight diverse U.S. health systems, the research analyzed 183,118 patients aged 20-80 years who were new users of specified antidepressants. The study focused on eight commonly prescribed antidepressants: sertraline (used as the reference treatment), citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, and venlafaxine. Employing a target trial emulation approach, the researchers estimated the effects of initiating each antidepressant on mean weight change at 6, 12, and 24 months after treatment initiation.

The study found small differences in mean weight change among the antidepressants (Figure). Compared to sertraline, estimated 6-month weight gain was higher for escitalopram (0.41 kg), paroxetine (0.37 kg), duloxetine (0.34 kg), venlafaxine (0.17 kg), and citalopram (0.12 kg). Fluoxetine showed a similar weight change to sertraline, while bupropion was associated with weight loss (-0.22 kg). Escitalopram, paroxetine, and duloxetine were associated with a 10-15% higher risk of gaining at least 5% of baseline weight, whereas bupropion was associated with a 15% reduced risk. .

The study utilized advanced statistical techniques, specifically inverse probability weighting of repeated outcome marginal structural models, to address potential biases from baseline confounding factors and selective outcome measurement. Researchers conducted both intention-to-treat and per-protocol analyses to provide a comprehensive evaluation. Medication adherence rates at the six-month mark showed considerable variation, with duloxetine having the lowest rate at 28% and bupropion the highest at 41%.

The findings suggest that clinicians should consider potential weight gain when initiating antidepressant treatment, particularly given the low adherence rates observed. Bupropion consistently showed the least weight gain among the medications studied. This information could help guide decision-making for patients and providers, especially for those with weight or metabolic health concerns.

The study was funded by the National Institutes of Health and published in the Annals of Internal Medicine on July 2, 2024. The results of this large-scale, real-world study contribute to the growing body of evidence on antidepressant-associated weight changes and may help inform clinical practice in the selection of first-line antidepressant treatments.

Reference:
Petimar J et al. Ann Intern Med. 2024;177(8):993-1003. Abstract.