Antidepressant treatment and weight gain

Evidence with respect to the weight gain associated with different antidepressants was investigated via an observational study (1):

• electronic health record (EHR) data from 2010 to 2019 across 8 U.S. health system
• 183,118 patients
• prescription data determined initiation of treatment with sertraline, citalopram, escitalopram, fluoxetine, paroxetine, bupropion, duloxetine, or venlafaxine
  • investigators estimated the population-level effects of initiating each treatment, relative to sertraline, on mean weight change (primary) and the probability of gaining at least 5% of baseline weight (secondary) 6 months after initiation
  • most common antidepressants prescribed were sertraline, citalopram, and bupropion
  • among selective serotonin reuptake inhibitors (SSRIs), escitalopram and paroxetine were associated with the greatest 6-month weight gain, whereas bupropion was associated with the least weight gain across all analyses
  • using sertraline as a comparator, 6-month weight change was lower for bupropion (difference, 0.22 kg) and higher for escitalopram (difference, 0.41 kg), duloxetine (difference, 0.34 kg), paroxetine (difference, 0.37 kg), and venlafaxine (difference, 0.17 kg)
  • escitalopram, paroxetine, and duloxetine were associated with 10% to 15% higher risk for gaining at least 5% of baseline weight, whereas bupropion was associated with 15% reduced risk
  • study limitations included:
    • study included data only on prescriptions and investigators could not verify whether the medications were dispensed or taken as prescribed
    • missing weight information because most patients did not encounter the health system at exactly 6, 12, and 24 months, only 15%-30% had weight measurements in those months
    • low adherence rates made it difficult to attribute relative weight change at the 12- and 24-month time points to the specific medications of interest
  • study authors concluded:
    • small differences in mean weight change were found between 8 first-line antidepressants, with bupropion consistently showing the least weight gain, although adherence to medications over follow-up was low

Previous evidence had noted (2):

• initiation of antidepressant drugs shows a strong temporal association with weight gain, which is greatest during the second and third years of treatment
• during the second year of treatment, the risk of ≥5% weight gain is 46.3% higher than in a general population comparison group
  • associations are consistent across a wide range of clinical, social, and demographic characteristics

Reference:

1. Young PJ et al. Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study. Ann Intern Med. 2024 Jul 2. doi: 10.7326/M23-2742.
2. Gafoor R, Booth HP, Gulliford MC. Antidepressant utilisation and incidence of weight gain during 10 years' follow-up: population based cohort study. BMJ. 2018 May 23;361:k1951