Antidepressant Weight Gain Is Lowest With Bupropion

Across 8 different first-line antidepressants, weight gain is lowest with bupropion, according to study results published in Annals of Internal Medicine.

Patients with major depressive disorder (MDD) who are treated with antidepressant medications often report weight gain as a side effect. However, evidence on comparative weight change for specific first-line treatments is scarce.

To fill this knowledge gap, researchers performed an observational cohort study to evaluate antidepressant weight gain over 24 months associated with sertraline, citalopram, bupropion, duloxetine, venlafaxine, paroxetine, escitalopram, and fluoxetine. The researchers used electronic health record data collected between 2010 to 2019 across 8 health systems in the United States to identify prescription data on adult patients (20-80 years of age) who received the 8 common, first-line antidepressant treatments of interest. Patients were required to have a weight measurement in the 3 months before initiation to establish a baseline weight, and those who received more than 1 antidepressant medication were excluded from analyses.

A total of 183,118 participants were included in the present study. Participants had a mean (SD) age of 48.2 (15.7) years, 65% were women, and 79% were White. Most individuals were diagnosed with either depression (36%) or anxiety (39%). The mean (SD) baseline weight of participants was 84.0 (23.0) kilograms.

“ Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma.

The investigators found that the most commonly initiated antidepressant were sertraline (20%), citalopram (16%), and bupropion (15%), while paroxetine was least commonly prescribed (4%). The median length of medication adherence was 4 months for most antidepressants, with the exception of paroxetine and duloxetine at 3 months.

Relative to sertraline, weight change at 6 months was lower for bupropion (-0.22 kg) and higher for escitalopram (0.41 kg), duloxetine (0.34 kg), paroxetine (0.37 kg), and venlafaxine (0.17 kg). The risk of gaining at least 5% of baseline weight was 15% lower for bupropion compared with sertraline, with a risk ratio (RR) of 0.85 (95% CI, 0.81-0.89). In contrast, the risk of weight gain was significantly higher for escitalopram (RR, 1.15), duloxetine (RR, 1.10), and paroxetine (RR, 1.14).

The researchers found that these results were largely replicated at longer time points, as the weight gain associated with bupropion was significantly lower than the weight gain associated with sertraline at both 12 months (-0.71 kg) and 24 months (-0.91 kg) after medication initiation. Duloxetine and venlafaxine were also associated with less weight gain than sertraline at 24 months (-0.69 kg and -0.59 kg, respectively).

Sensitivity analyses confirmed these findings, demonstrating greater weight reduction for bupropion relative to sertraline when accounting for baseline depression or anxiety.

The investigators concluded, “Clinicians and patients could consider these differences when making decisions about specific antidepressants, especially given the complex relationships of obesity and depression with health, quality of life, and stigma.”

Study limitations include a lack of data on mediation dispensing, incomplete data on medication adherence, and low medication adherence across antidepressants.

Disclosure: Some study authors reported affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.