Remission outcomes with bupropion versus selective serotonin reuptake inhibitor monotherapy in major depressive disorder with comorbid obesity: A propensity-matched cohort analysis
In brief
Bupropion achieves remission in 8.5% of obese depressed patients versus 7.9% with SSRIs
In a propensity-matched analysis of 165,629 adults with major depression and obesity, bupropion monotherapy led to a modestly higher remission rate (8.5%) than selective serotonin reuptake inhibitors (7.9%). The difference, though statistically significant, is small, and prospective trials with objective remission measures are needed before changing prescribing habits.
- Journal
- Journal of affective disorders (Q1)
- Published
- 20 August 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Farah Khorassani, Justin Schneider, Jonathan Prunean, Gemma Espejo
- PMID
- 42624215
- DOI
- 10.1016/j.jad.2026.122398
Why clinicians should know about it
- Picked for Psychiatry and Mental Health (paper of the day, 22 August 2026): Bupropion shows modestly higher remission than SSRIs in obese MDD
Abstract
Observational and secondary analyses of clinical trials evaluating efficacy of antidepressants suggest that medications with noradrenergic and dopaminergic mechanisms of action may be more effective in managing symptoms of major depressive disorder (MDD) in obese patients than medications that are purely serotonergic. The purpose of this study is to compare the efficacy of bupropion versus SSRIs in patients without a documented antidepressant trial with comorbid MDD and obesity. This was a retrospective, propensity-score matched, observational study utilizing a global cohort within the TriNetX database. Adults aged 18 or over with a major depressive episode and obesity were grouped into two cohorts: 1) exposure to bupropion and 2) exposure to SSRIs. Patients with antidepressant exposure prior to the index event were excluded. Both cohorts were propensity matched based on 16 covariates. The primary outcome was remission of a major depressive episode. Secondary outcomes included evaluating socioeconomic and psychosocial differences between the groups. Each cohort yielded 165,629 patients. The primary endpoint analysis indicated a small but statistically significant difference in MDD remission rates in favor of bupropion with an absolute risk rate of 8.5% compared to 7.9% in the SSRI group (Risk Ratio [RR] 1.07, 95% CI 1.05-1.10, p < 0.0001). Binary outcomes were summarized using risk differences and risk ratios and compared between cohorts using chi-square tests. Our findings suggest bupropion monotherapy was associated with a small but statistically significant higher remission rate compared with SSRIs but further prospective studies using objective remission indicators are needed.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.