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Clinical benefits and considerations of dextromethorphan and bupropion administered separately for managing depression: A case report.

Parna Haghparast, Busuyi Olotu, Carol Yuan

The mental health clinician February 1, 2026 DOI: 10.9740/mhc.2026.02.030 via PubMed

Summary

AI-generated from the abstract

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.

Study at a glance

Characteristics Case report Peer reviewed
Sample size 1
Population 31-year-old male with treatment-resistant depression and alcohol use disorder
Interventions bupropion dextromethorphan
Topics Depression
Keywords Bupropion Cost Dextromethorphan Over the counter
Key finding A 31-year-old man with treatment-resistant depression and alcohol use disorder experienced symptom improvement on bupropion and dextromethorphan.

Abstract

MDD can affect anyone regardless of age, and it often starts during late teens or early adulthood. Although some patients with MDD have an adequate response to medications, only approximately 50% respond to the first treatment, and approximately 30% do not achieve remission despite multiple interventions. Several strategies exist for treating patients who have failed multiple first-line agents, including switching to first-generation antidepressants or to antidepressants unavailable in generic. Other options include augmenting the current antidepressant with other medications such as antipsychotics. Alternatively, augmentation with electroconvulsive therapy, transcranial magnetic stimulation, or esketamine nasal spray can be considered. Prescribing antidepressants unavailable in generic limits accessibility to patients due to cost and prior authorization process. Dextromethorphan/bupropion, a new combination therapy, has shown promise in the treatment of MDD with efficacy seen as early as week 1. Although commercially available, cost and insurance limitations may necessitate consideration of separate administration of its components. This case report describes a 31-year-old male with a history of treatment-resistant depression and alcohol use disorder who experienced symptom improvement on bupropion and dextromethorphan. This case shares observations and clinical considerations of using such combinations in the management of treatment-resistant depression in the context of substance use disorder.

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