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

Mahak Aggarwal, Jawahar Singh, Khushpreet Kaur, Mohit Thakur, Rohit Guleria

Indian Journal of Psychiatry February 1, 2026 DOI: 10.4103/indianjpsychiatry_979_25 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Case study Case report Peer reviewed
Sample size 3
Population Male patients with alcohol or opioid dependence and depression
Intervention dextromethorphan-bupropion
Topics Addiction Depression
Keywords Anhedonia Antidepressants Dextromethorphan-bupropion
Key findings Dextromethorphan-bupropion led to substantial improvement in depressive symptoms and functioning in three male patients with dual-diagnosis depression after multiple failed antidepressant trials.

Abstract

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. 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. These findings highlight the clinical implications of dextromethorphan-bupropion in dual-diagnosis depression and warrant further controlled studies to establish efficacy and safety.

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Electroconvulsive Therapy, Ketamine, and Esketamine in a Patient with Major Depressive Disorder and Multiple Comorbidities: A Case Report over 10-year Treatment from Adolescence to Adulthood. A patient with treatment-resistant depression and comorbid generalized anxiety... 2025 Case report n = 1
Oral Administration of the NMDA Receptor Antagonist S-Ketamine as Add-On Therapy of Depression: A Case Series Four depressed patients taking standard antidepressants 2009 Case series n = 4
A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment‐resistant depression Patients with enduring eating disorders and treatment-resistant depression 2021 Case series n = 4
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Case report: Intramuscular ketamine or intranasal esketamine as a treatment in four patients with major depressive disorder and comorbid anorexia nervosa Patients with anorexia nervosa and a comorbid depressive disorder treated at a private... 2023 Case report n = 4

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