Efficacy of Dextromethorphan-Bupropion Versus SSRIs in the Treatment of Major Depressive Disorder

Efficacy of Dextromethorphan-Bupropion Versus SSRIs in the Treatment of Major Depressive Disorder: A Randomized Controlled Trial

The study aims to compare the antidepressant effects of a dextromethorphan-bupropion combination versus standard SSRI therapy in adult patients with major depressive disorder. Participants will be randomized into two groups: one receiving dextromethorphan-bupropion and the other receiving an SSRI (e.g., sertraline or escitalopram). Treatment will last for 6 weeks, with assessments at baseline and study completion. The primary outcome will be the remission rate measured by a validated depression rating scale. Secondary outcomes include change in depressive symptoms severity and safety/tolerability measures.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Drug: Dextromethorphan-Bupropion; Drug: SSRIs

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • KPK
    • Nowshera, KPK, Pakistan, 25770
      • Combined Military Hospital
    • Nowshera, KPK, Pakistan, 25770
      • Department of Psychiatry, Combined Military Hospital Nowshera

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Diagnosed with major depressive disorder (MDD) per DSM-5 criteria.

Baseline depression score indicating moderate to severe depression

Ability to provide informed consent

Willing to comply with study requirements

Exclusion Criteria:

History of bipolar disorder, schizophrenia, or other psychotic disorders

Current substance use disorder (within past 6 months)

Active suicidal ideation requiring urgent intervention

Pregnancy or breastfeeding

Known hypersensitivity to study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dextromethorphan-Bupropion Group; Participants will receive a fixed-dose combination of dextromethorphan-bupropion, dosed according to approved guidelines for major depressive disorder, administered orally for 6 weeks.	Drug: Dextromethorphan-Bupropion; Participants will receive a fixed-dose combination of dextromethorphan-bupropion, dosed according to approved guidelines for major depressive disorder, administered orally for 6 weeks.
Active Comparator: SSRI Group; Participants will receive an SSRI at standard therapeutic doses, administered orally for 6 weeks.	Drug: SSRIs; Participants will receive an SSRI at standard therapeutic doses, administered orally for 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Depression Severity (measured by HAMD-17)	Change from baseline in depressive symptom scores, measured using the Hamilton Depression Rating Scale, 17-item version (HAMD-17; score range 0-52, with higher scores indicating worse depression severity).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission Rate	Proportion of participants achieving remission, defined as a depression rating scale score below the clinical threshold.	6 weeks

Collaborators and Investigators

• Sponsor: Asad Ullah Jan
• Collaborators: Combined Military Hospital Nowshera

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2025
• Primary Completion (Actual): November 30, 2025
• Study Completion (Actual): December 31, 2025

Study Registration Dates

• First Submitted: April 26, 2025
• First Submitted That Met QC Criteria: April 26, 2025
• First Posted (Actual): May 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Membrane Transport Modulators; Neurotransmitter Uptake Inhibitors; Serotonin Agents; Pharmacologic Actions; Chemical Actions and Uses; Selective Serotonin Reuptake Inhibitors
• Other Study ID Numbers: CMHNSR-REF-16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to confidentiality concerns and lack of infrastructure for data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No