NCT07523048

Dextromethorphan-Bupropion on Striatal Activity in Adults With Major Depressive Disorder

Two-Week, Open-Label, Exploratory Neuroimaging Study Evaluating the Effect of Dextromethorphan-HBr Bupropion-HCl on Striatal Reactivity During Reward Processing in Adults With Major Depressive Disorder

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Roger McIntyre · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

This study will look at how a new medication (dextromethorphan and bupropion taken together in one pill) affects the brain in people with depression. All participants will take the medication for two weeks and have brain scans done. Since people with depression often feel reduced enjoyment in day-to-day activities, our goal is to learn if this treatment can change brain activities in ways that could help improve mood and enjoyment in life.

Detailed description

Dextromethorphan-bupropion (DXM/BUP) is a novel, rapid-acting, glutamatergic antidepressant approved by the US FDA in the treatment of adults with MDD, with clinical evidence of antidepressant effect within two weeks of administration. This pilot, two-week, open-label neuroimaging study will examine the effect of DXM/BUP on striatal activity in adults with major depressive disorder (MDD). The region of interest is the striatum, a core structure in the human reward circuit. Adults with a primary diagnosis of MDD currently experiencing a moderate-severe major depressive episode will receive open-label DXM/BUP (150 mg orally, twice daily) for 14 days. Task-based functional MRI scans will be conducted at baseline (Day 1, prior to treatment) and at primary endpoint (Day 14, following treatment) to evaluate changes in striatal activation. During each scan, participants will perform the Effort Expenditure for Rewards Task (EEfRT), a validated measure of reward motivation and effort-based decision-making that is particularly sensitive to anhedonia. Changes in striatal activation associated with open-label DXM/BUP treatment in adults with MDD will be evaluated by comparing pre-treatment and post-treatment fMRI blood-oxygenation level-dependent (BOLD) measures.

Conditions

• Major Depressive Disorder (MDD)

Interventions

Type	Name	Description
DRUG	Dextromethorphan-Bupropion	The generic name of the study drug is dextromethorphan-bupropion (150 mg), which is an oral, extended-release tablet comprised of 45 mg dextromethorphan HBr and 105 mg bupropion HCl. The brand name of this study drug is Auvelity. Eligible participants that provide written informed consent will be assigned to a single-arm, open-label treatment group, for a treatment period of 14 days. Participants in this treatment group will be asked to take one oral dextromethorphan-bupropion extended-release tablet once daily for Days 1-3 of the treatment period. Participants will then be asked to increase their dose to one oral dextromethorphan-bupropion extended-release tablet twice daily, for Days 4-14 of the treatment period.

Timeline

• Start date: 2025-11-21
• Primary completion: 2026-07-01
• Completion: 2027-01-01
• First posted: 2026-04-13
• Last updated: 2026-04-13

Locations

1 site across 1 country: Canada

Regulatory

• FDA-regulated drug study