Efficacy and safety of dextromethorphan–bupropion combination (AXS-05) in the treatment of depression: A systematic review and network meta-analysis

This network meta-analysis evaluated the efficacy and safety of the dextromethorphan–bupropion combination (AXS-05) in treating major depressive disorder (MDD). Data were retrieved from multiple databases, including PubMed, Embase, Scopus, Google Scholar, and ClinicalKey, yielding 60 records. After removing duplicates and excluding irrelevant studies, such as reviews, case reports, posters, and studies focusing on unrelated populations (e.g., Alzheimer’s dementia), two randomized controlled trials (RCTs) – Tabuteau et al. (2022) and Iosifescu et al. (2022) – were selected for final analysis. The inclusion criteria focused on RCTs published between 2014 and 2024, involving adult participants (18–65 years) diagnosed with MDD, and reporting on the efficacy and safety of the dextromethorphan–bupropion combination. Studies that did not focus on MDD, were not in English, or lacked control groups were excluded. The findings indicate superior efficacy of the dextromethorphan–bupropion combination, with remission rates of 46.5% and 39.5%, compared to 16.2% for Bupropion alone and 17.3% for placebo. Despite a higher incidence of mild to moderate adverse events (72.9% vs. 64.6% for Bupropion), the combination’s safety profile remained comparable, with no significant increase in treatment discontinuation. These results suggest that AXS-05 is a promising treatment for MDD, warranting further investigation in larger, diverse populations to confirm its long-term efficacy and safety.