REAL-WORLD CLINICAL OUTCOMES OF PATIENTS SWITCHING TO TREATMENT WITH DEXTROMETHORPHAN-BUPROPION (45 MG/105 MG)

Introduction

Dextromethorphan-bupropion (45 mg/105 mg) (Auvelity®) is an oral, N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 agonist approved in the US for the treatment of adults with major depressive disorder (MDD). This study evaluated real-world clinical outcomes after initiation of dextromethorphan-bupropion.

Methods

Adults initiating dextromethorphan-bupropion were identified in US electronic health record (EHR) data collected between August 2022 and March 2025. Outcomes including the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 2-item (GAD-2), Clinical Global Impressions–Severity (CGI-S), and CGI–Improvement (CGI-I) scales, as well as body weight, were evaluated using pairwise comparisons between index (1st Auvelity prescription) and multiple follow-up timepoints.

Results

Among the 217 patients initiating dextromethorphan-bupropion (58% female; mean age: 43 years), most had comorbid anxiety (88.5%) and/or ADHD (79.3%). Sleep disorders were also common, affecting 45.2% of patients, including insomnia in 37.8% and sleep apnea in 11.1%. Metabolic disorders were reported in 21.2%. Most patients (86.6%) had previously used MDD-related treatments; their last MDD-related treatments before starting dextromethorphan-bupropion were SSRIs (35.0%), NDRIs (19.4%), SNRIs (18.4%), antipsychotics (14.3%), and esketamine (5.5%). Dextromethorphan-bupropion was initiated as a monotherapy in 71.9% of the patients. At baseline, patients predominantly fell within the moderate-to-severe range of depressive symptoms (26.6%, moderate; 19.7%, moderately severe; 11.7%, severe); the mean PHQ 9 score was 11.48. Improvements in all outcomes were observed starting from Week 1 after dextromethorphan-bupropion initiation and were significant (P < 0.05) at Week 2, Week 6, and Month 3, including mean changes in GAD-2 (-0.88, -0.74, and -0.89, respectively). For CGI-I scores, 78.0%, 82.5%, and 83.9% of patients showed improvement at Week 2, Week 6, and Month 3, respectively. Body weight remained stable throughout the evaluation period. Significant reductions in PHQ-9 total score (-2.27, 2.97, -3.27; all P < 0.05) and anhedonia, as measured by PHQ-9 Item 1, (-0.33, -0.47, -0.48; all P < 0.05) were observed at Week 2, Week 6, and Month 3, respectively.

Conclusions

In this retrospective EHR analysis, adult patients switching to dextromethorphan-bupropion demonstrated rapid and lasting improvements in both patient-and clinician-rated outcomes over 3 months. Most patients had mental-health related comorbidities and attempted various MDD-related treatments; 80% initiated dextromethorphan-bupropion as a monotherapy.