Dextromethorphan-bupropion combination in depression with dual diagnosis: Insights from a case series

Background: Major depressive disorder and co-morbid substance use disorder represent a challenging dual diagnosis, characterized by persistent anhedonia, high relapse rates, and poor response to conventional antidepressants. The dextromethorphan-bupropion combination with synergistic glutamatergic and dopaminergic mechanisms provides a new treatment option. Cases: We present three male patients with alcohol or opioid dependence and depression who showed substantial improvement in depressive symptoms and functioning with dextromethorphan-bupropion after multiple failed antidepressant trials. Conclusion: These findings highlight the clinical implications of dextromethorphan-bupropion in dual-diagnosis depression and warrant further controlled studies to establish efficacy and safety.