Key Takeaways
Extended Takeaways
- In this 6-week trial, patients started dextromethorphan-bupropion 45 mg-105 mg once daily for 3 days and then twice daily thereafter, with a significant advantage over placebo on the primary endpoint by week 6 (least-squares mean difference, −3.87; 95% confidence interval [CI], −1.39 to −6.36; P = .002).
- Early efficacy was accompanied by early remission: at week 2, remission rates were 16.9% with dextromethorphan-bupropion versus 7.5% with placebo (treatment difference, 9.4%; 95% CI, 1.9%–16.8%; P = .013).
- By week 6, both remission and response separated meaningfully from placebo, with remission in 39.5% versus 17.3% and clinical response in 54.0% versus 34.0%, suggesting benefit beyond symptom score change alone.
- Functional and patient-reported outcomes also improved, with statistically significant advantages versus placebo on QIDS-SR-16, MADRS-6, Q-LES-Q-SF, and PGI-I at all time points, and on the Sheehan Disability Scale at week 2 and every time point thereafter.
- Adverse events were more common with dextromethorphan-bupropion than placebo (61.7% vs 45.1%), and discontinuations due to adverse events were 6.2% versus 0.6%, so clinicians should balance the efficacy signal with somewhat higher early tolerability burden.
- The study population excluded treatment-resistant depression, psychotic or bipolar disorders, substance use disorder within the past year, clinically significant risk of suicide, and seizure history, so applicability is strongest for nonpsychotic MDD without these complicating features.
