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antidepressant treatment and weight gain

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

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


  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

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