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Annals of Internal MedicineMedication-Induced Weight Change Across Common Antidepressant Treatments: A Target Trial Emulation Study

Comparative Analysis of Weight Change Among First-Line Antidepressants: Implications for Clinical Practice

A recent observational cohort study examined the weight change associated with eight commonly prescribed first-line antidepressants over a 24-month period, using electronic health record data from eight US health systems. The study found small but significant differences in weight change among the medications, with bupropion showing the least weight gain. This information is crucial for clinicians when considering the potential impact of antidepressant treatment on patients’ weight.

Study Design:

  • Participants: 183,118 patients initiating treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine.
  • Setting: Electronic health record (EHR) data from 2010 to 2019 across eight US health systems.
  • Duration: 24-month observational cohort study.
  • Measurements:
    • Prescription data to determine the initiation of antidepressant treatment.
    • Primary outcome: Mean weight change 6 months after initiation.
    • Secondary outcome: Probability of gaining at least 5% of baseline weight.
    • Analysis method: Inverse probability weighting of repeated outcome marginal structural models to account for baseline confounding and informative outcome measurement.

Key Findings:

  • Weight Gain Comparison to Sertraline:
    • Escitalopram: +0.41 kg (95% CI, 0.31 to 0.52 kg)
    • Paroxetine: +0.37 kg (95% CI, 0.20 to 0.54 kg)
    • Duloxetine: +0.34 kg (95% CI, 0.22 to 0.44 kg)
    • Venlafaxine: +0.17 kg (95% CI, 0.03 to 0.31 kg)
    • Citalopram: +0.12 kg (95% CI, 0.02 to 0.23 kg)
    • Fluoxetine: -0.07 kg (95% CI, -0.19 to 0.04 kg)
    • Bupropion: -0.22 kg (95% CI, -0.33 to -0.12 kg)
  • Risk of Gaining at Least 5% of Baseline Weight:
    • Higher for escitalopram, paroxetine, and duloxetine (10% to 15% increase).
    • Reduced for bupropion (15% decrease).
  • Adherence:
    • Six-month adherence ranged from 28% (duloxetine) to 41% (bupropion).
  • Limitations:
    • Lack of data on medication dispensing.
    • Low medication adherence.
    • Incomplete data on adherence and weight measures over time.

HCN Medical Memo
Clinicians should consider potential weight gain when prescribing antidepressants. This study provides evidence that bupropion is associated with the least weight gain among the first-line treatments, which may be a key consideration for patients concerned about weight changes.

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