Clinical benefits and considerations of dextromethorphan and bupropion administered separately for managing depression: A case report.
The mental health clinician February 1, 2026 Parna Haghparast, Busuyi Olotu, Carol Yuan
Only about half of people with major depressive disorder respond to their first antidepressant, and around 30% do not achieve remission despite multiple treatments. For those who fail several first-line agents, options include switching to older or non-generic antidepressants, augmenting with antipsychotics, or using electroconvulsive therapy, transcranial magnetic stimulation, or esketamine. Non-generic antidepressants can be costly and require prior authorization. A new combination therapy, dextromethorphan/bupropion, has shown early promise, with efficacy seen as early as week one, but cost and insurance limits may lead to using its components separately. This case report describes a 31-year-old man with treatment-resistant depression and alcohol use disorder whose symptoms improved on bupropion and dextromethorphan, offering observations for managing such cases.