Weight changes with first-line antidepressants: A 24-month observational cohort study

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Created On: 23/01/2025

Antidepressants are widely prescribed, but there is limited evidence comparing weight changes across specific first-line treatments.

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Key take away

Weight gain varies slightly across first-line antidepressants, with Bupropion showing the least increase. Clinicians may consider the possibility of weight gain when selecting antidepressant treatments.

Background

Antidepressants are widely prescribed, but there is limited evidence comparing weight changes across specific first-line treatments. This observational cohort study spanning 24 months was carried out to evaluate weight fluctuations linked with common first-line antidepressants by simulating a target trial.

Method

This study included electronic health record data from 8 U.S. health systems and 183,118 patients. Antidepressant initiation was identified through prescription data for Bupropion, Citalopram, Duloxetine, Escitalopram, Fluoxetine, Paroxetine, Sertraline, and Venlafaxine.

Population-level effects were estimated relative to Sertraline for mean weight alteration (primary outcome) and for the likelihood of procuring a minimum of 5% of baseline weight (secondary outcome) within six months. Marginal structural models with inverse probability weighting were applied. This approach addressed baseline confounding and informative outcome measurement. Secondary analyses delved into the effects of initiation and adherence to each treatment.

Result

Compared with Sertraline, the projected 6-month weight gain was greater for Escitalopram (0.41 kg), Paroxetine (0.37 kg), Duloxetine (0.34 kg), Venlafaxine (0.17 kg), and Citalopram (0.12 kg); similar for Fluoxetine (−0.07 kg); and lower for Bupropion (−0.22 kg). Duloxetine, Escitalopram, and Paroxetine escalated the likelihood of gaining at least 5% of baseline weight by 10% to 15%. On the other hand, Bupropion was linked with a 15% diminished likelihood. The estimates of initiation and adherence effects illustrated stronger associations but wider confidence intervals. Adherence rates at 6 months ranged from 28% (for Duloxetine) to 41% (for Bupropion).

Conclusion

Minor variations in weight alteration were observed among eight first-line antidepressants, with Bupropion usually associated with the least weight gain. Weight gain considerations may guide antidepressant selection in clinical practice.