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

Recruiting now · Phase 2

Conditions studied: Major Depressive Disorder (MDD)

In brief

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.

Key facts

Study ID

NCT07523048

Run by

Roger McIntyre

People needed

30

Starts

2025-11-21

Expected to finish

2027-01-01

Last updated by the study team

2026-04-13

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Capable of providing voluntary, written, informed consent prior to study enrollment.
• Male or female between the age of 18 to 65 years, inclusive.
• Meets DSM-5-TR criteria for a Major Depressive Disorder and currently experiencing a Major Depressive Episode (MDE) without psychotic features. Diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI) conducted by a delegated physician or trained research study staff.
• Must present with a current MDE with moderate to severe intensity, as determined by the Montgomery-Åsberg Depression Rating Scale (MADRS) total score equal to or greater than 21 and Clinical Global Impression Scale-Severity (CGI-S) total score equal to or greater than 4.
• Lifetime history of less than five prior adequate trials of a pharmacologic treatment for depression.
• Deemed safe and eligible by the study doctor, study investigator, trained research staff and/or fMRI technicians/trained staff to participate in fMRI scans according to intake screening form and (if applicable) related medical documentation (e.g., doctor notes, medical charts documenting medical/dental implants, pacemakers).
• Access to reliable internet for the entire study period and an internet-based device (i.e., a smartphone, laptop, desktop or tablet).
• Must have the ability to speak and read English. This is due to the diagnostic and study assessments being administered in English.
• Note: there is no inclusion/exclusion based on prior history of manual-based psychotherapy (e.g., cognitive behavioural therapy).

You may not qualify if…

• Currently has symptoms of mania or hypomania or mixed state bipolar disorder, as determined by the Young Mania Rating Scale (YMRS) score greater than 12.
• Current symptoms of psychosis or a substance use disorder within the past 12 months. Other select secondary psychiatric comorbidities (e.g. anxiety disorders, trauma-related disorders) will not be excluded according to the clinical judgment of an investigator.
• Lifetime history of a primary psychotic disorder (including, but not limited to, schizophrenia or schizoaffective disorder).
• Failure of five or more prior trials of pharmacological treatment for depression.
• Lifetime history of failure of electroconvulsive therapy (ECT) or repetitive transcranial magnetic stimulation (rTMS).
• Lifetime history of treatment with intravenous racemic ketamine and/or intranasal esketamine for depression.
• History of non-response to a prior trial of dextromethorphan-bupropion
• Hypersensitive to bupropion in any formulation
• Duration of current MDE greater than 2 years
• Recreational cannabis use daily, weekly or cannabis use disorder.
• History of neurological disorders (including, but not limited to, uncontrolled seizure disorder, history of stroke within past 12 months, major head injuries, aneurysmal vascular disease [including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels], arteriovenous malformation, or intracerebral hemorrhage).
• Are actively suicidal (e.g., any suicide attempts within the past 12 months) or are at serious suicidal risk as indicated by any current suicidal intent, including a plan, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) (score of "YES" on suicidal ideation Item 4 or 5 within 3 months prior to Visit 1 [Screening]) and/or based on clinical evaluation by the Investigator; or are homicidal, in the opinion of the Investigator. Participants who are currently hospitalized for MDD symptoms or suicidality are not allowed into the study.
• Pregnant or breastfeeding women or women who intend to become pregnant in the next 6 months. Patients who are sexually active must agree to use a highly effective contraceptive method (as outlined in section 9.7).
• Current or history of severe hepatic or renal impairment.
• Use of prohibited concomitant medications [e.g., antidepressants, monoamine oxidase inhibitors (MAOIs), CYP2B6 or CYP2D6 inhibitors]. See section 9 for details on contraindications, side effects, prohibited concomitant medication, warnings and precautions with the investigational agent.
• Any medical or psychiatric history that may exclusionary for fMRI scanning, including but not limited to:
• Cardiac pacemaker
• Surgical aneurysm clips
• Neurostimulator
• Implanted pumps
• Metal fragments in body/eyes
• Pregnancy
• Nitroglycerin patch
• Certain cochlear implants
• Weight> 440 lbs

Where it is running

• Brain and Cognition Discovery Foundation — Toronto, Ontario, Canada (enrolling)

Full record on ClinicalTrials.gov

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