Three Dosing Regimens of Dextromethorphan (DXM) Reportedly Used in Major Depressive Disorder

An Open-Label Tolerance Study of Three Dosing Regimens of Dextromethorphan (DXM) Reportedly Used in Major Depressive Disorder

This is an open-label dosing pilot study of 15 patients aged 18-50 years of age with diagnoses of Major Depressive Disorder (MDD) randomized to 1 of 3 treatment arms.

The study will consist of a screening evaluation performed within the course of 2 weeks, followed by an active treatment period of 28 days where treatment arm 1 will take a supervised dose of 300mg DXM every 14 days for 28 days, treatment arm 2 will take the FDA approved maximum daily ingestion for cough (60mg DXM) daily for 28 days, and treatment arm 3 will take 1 supervised dose of 300mg DXM and 60mg for the remaining 28 days. After the active treatment period, subjects will be followed for 65 days with safety and psychiatric assessments at designated timepoints.

Study Overview

• Status: Completed
• Conditions: Smoking; Smoking Cessation; Treatment Resistant Depression; MDD
• Intervention / Treatment: Drug: Dextromethorphan

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must be a man or woman, 18 to 50 years, inclusive
• Subject must meet Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria for MDD without psychotic features based on clinician assessment.
• Subjects must have undergone 3 or fewer antidepressant trials
• Subjects must have moderate to severe depression as determined by a screening Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or greater

Exclusion Criteria:

• Subject has a current diagnosis of Bipolar Affective Spectrum Disorder, obsessive compulsive disorder, or a DSM-V personality disorder
• Subject has had an incomplete response to more than 3 antidepressant trials
• Subject cannot tolerate 60mg DXM as determined by study physician
• Subject meets DSM-5 severity criteria for moderate or severe substance or alcohol use disorder within 6 months of screening, excluding caffeine or nicotine
• Subject has a current clinical diagnosis of autism, dementia, or intellectual disability
• Subject has history of psychosis not attributable to organic/metabolic causes
• Subject has a history of serotonin syndrome or sensitivity
• Subject has taken venlafaxine or a monoamine oxidase inhibitor (MAOI) within 4 weeks prior to screening
• Subject is actively taking an opiate antagonist for any indication
• Subject is taking a higher-than-recommended dosage of serotonergic antidepressant [including but not limited to selective serotonin reuptake inhibitor (SSRI), serotonin-norepinephrine reuptake inhibitor (SNRI), serotonin partial agonist/reuptake inhibitor (SPARI), serotonin antagonist and reuptake inhibitor (SARI) within 4 weeks prior to screening
• Subject is actively suicidal
• Subject has participated in another clinical drug trial within 6 months prior to screening
• Subject has a history or current signs of liver or renal insufficiency
• Subject has a clinically significant condition of any organ system that might adversely impact subject health upon consumption of DXM
• Subject has previous history of intolerance to ketamine or its enantiomers
• Subject has previous history of incomplete antidepressant response to ketamine or its enantiomers
• Subject is currently using DXM for any indication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 1; 60 mg DXM a day for 28 days	Drug: Dextromethorphan; Dextromethorphan will be administered and its tolerability evaluated.
Experimental: Dose 2; 300 mg DXM every 2 weeks for 28 days.	Drug: Dextromethorphan; Dextromethorphan will be administered and its tolerability evaluated.
Experimental: Dose 3; 300mg DXM once, with 60mg DXM daily afterwards	Drug: Dextromethorphan; Dextromethorphan will be administered and its tolerability evaluated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to All-Cause Discontinuation of Dextromethorphan	This will be measured in days from the first administration of the drug until discontinuation.	Up to 90 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Anupama Kumar, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2020
• Primary Completion (Actual): December 7, 2021
• Study Completion (Actual): December 7, 2021

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 9, 2020
• First Posted (Actual): January 13, 2020

Study Record Updates

• Last Update Posted (Actual): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 1, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Respiratory System Agents; Antitussive Agents; Dextromethorphan
• Other Study ID Numbers: IRB00192193

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes