REVIEW OF: Petimar J et al, Ann Intern Med 2024;177(8):993–1003

STUDY TYPE: Retrospective cohort 

When patients ask about weight changes with antidepressants, providing guidance can be challenging. While bupropion is often considered weight-neutral and paroxetine an offender, how do other common antidepressants compare? This large observational study offers insights.

The study reviewed 10 years of data from 183,118 adults ages 20–80 years who started on a single ­antidepressant. Patients with weight-related health conditions (eg, cancer) were excluded to avoid confounding factors. Using statistical methods to simulate a randomized trial, the researchers compared sertraline—the most commonly prescribed antidepressant—with seven other medications: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, and venlafaxine. Weight change at six months was the primary outcome. Weight changes at 12 and 24 months, and “significant” weight gain (an increase of 5% or more from baseline), were secondary outcomes.

At six months, some antidepressants showed small but measurable differences in weight effects compared to sertraline:

Bupropion: Associated with an average weight loss of 0.5 pounds and a 15% reduced likelihood of significant weight gain

Escitalopram, paroxetine, and duloxetine: Linked to an average weight gain of 0.8 pounds and a 10%–15% increased risk of significant weight gain

Fluoxetine: No significant difference

Notably, only 15% of participants had recorded weight measurements at six months, and participants’ adherence to antidepressant regimens was inconsistent, which limits the reliability of these findings.

CARLAT TAKE

This study was observational and had significant limitations, but it suggests that weight-related differences between antidepressants are modest at best. The changes observed here are unlikely to have a meaningful impact on most patients.