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COMPARATIVE EFFICACY OF BUPROPION VS SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN ANTIDEPRESSANT-NAIVE, OBESE PATIENTS WITH MAJOR DEPRESSIVE DISORDER

Farah Khorassani — Justin Schneider2, Jonathan Prunean3, Gemma Espejo2 1University of California, Irvine School of Pharmacy and Pharmaceutical Sciences, 2University of California, Irvine School of Medicine, 3UCI Alpha Clinic

2026 ASCP Annual Meeting

Background

Antidepressant drug selection in patients with co-morbid obesity is not well-studied. 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. Bupropion, a dopamine and noradrenergic reuptake inhibitor, indicated for MDD also induces weight loss and has demonstrated efficacy in inducing remission when added to an SSRI in obese patients in secondary analyses.

Objective

The purpose of this study is to compare the efficacy of bupropion versus SSRIs in antidepressant-naïve, obese patients with major depressive disorder.

Methods

This was a retrospective observational study utilizing a global cohort of 169 Health Care Organizations grouped into a network within the TriNetX database. Adults aged 18 or over with a diagnosis of a major depressive episode and obesity were grouped into two cohorts: 1) exposure to bupropion (n=166,271) and 2) exposure to SSRIs (n=1,016,277). In both cohorts, pregnant patients given antidepressants prior to their initial MDD diagnosis were excluded. Patients who received antidepressants prior to their first exposure to bupropion or SSRI were also excluded. Both cohorts were propensity matched based on 16 covariates including demographics, comorbid conditions such as anxiety disorders, and medication use such as antipsychotic use. The primary outcome was remission of a major depressive episode. Secondary outcomes included evaluating socioeconomic and psychosocial differences between the groups. Outcomes were observed up to five years after an initial intersectional history of MDD, obesity, and antidepressant intervention.

Results

After propensity matching, 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). A small but statistically significant difference was observed in the secondary composite outcome of socioeconomic and psychosocial health hazards, with a higher incidence among individuals receiving SSRIs compared with those receiving bupropion with absolute risk of 6.8% and 5.8%, respectively (RR 0.86, 95% CI 0.840.88, log-rank p < 0.0001). Kaplan-Maier analysis showed that patients receiving bupropion achieved MDD remission 15% faster than those on SSRIs (Hazard Ratio [HR] 1.15, 95% CI 1.12-1.18, p < 0.0001).

Conclusion

In this large, propensity-matched retrospective observational cohort study of antidepressant-naïve adults with obesity and major depressive disorder, bupropion monotherapy was associated with a small but statistically significant higher rate of remission compared with SSRIs. Additionally, SSRI treatment was associated with a slightly higher incidence of socioeconomic and psychosocial health hazards. Further prospective investigation is needed to assess the clinical significance of these differences in conjunction with other objective remission indicators.