Repurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder

NCT05181527 | Completed Phase 4

• 1 other identifier: AIIMSBBSR/PGThesis/21-22/74
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Therapeutic latency, lack of efficacy, and adverse drug reactions are the major concerns in current antidepressant therapies. One-third of the patients with major depressive disorder do not respond to conventional antidepressants that act through the monoaminergic system. To overcome these treatment hurdles, add-on therapy to standard antidepressant drugs may lead to better therapeutic outcomes. The recent discovery of the rapid and sustained antidepressant effect of subanesthetic dose of ketamine led to many extensive clinical and preclinical research in the recent past and has established the possibilities of NMDA receptors as a potential drug target for depression. As repeated doses of ketamine are related to abusive potential and adverse effects, the search for a similar antidepressant agent with a better safety profile is essential. Dextromethorphan has the property of noncompetitively blocking N-methyl-D-aspartate receptors (like ketamine) with additional serotonin transporter and norepinephrine transporter inhibitory action. So, the investigators expect that adding dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) regimen can improve clinical outcomes in major depressive disorder. The literature search found that to date, there is no randomized controlled trial on Dextromethorphan as add-on therapy to first-line antidepressants like SSRIs. So, the present randomized controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to SSRIs in major depressive disorder.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in severity in depressive symptoms

  Will be assessed by Montgomery-Asberg Depression Rating Scale score. The overall score ranges from 0 to 60. A higher score denotes greater severity of depression.

  Baseline and 8 weeks

Secondary Outcomes (6)

• To evaluate treatment response rate

  8 weeks

• To evaluate the symptom remission rate

  8 weeks

• Severity of depressive symptoms at baseline

  At baseline

• To evaluate the improvement in symptoms of depression

  8 weeks

• To evaluate the neurotrophic effect of the treatment

  Baseline and 8 weeks

Study Arms (2)

Control group

PLACEBO COMPARATOR

Patients in the control group will get an identical-looking capsule containing placebo (starch) once daily in addition to SSRI.

Drug: Selective Serotonin Reuptake Inhibitors; Drug: Placebo

Test group

EXPERIMENTAL

Patients in the test group will get Dextromethorphan 30 mg once daily orally as an add-on to ongoing SSRI treatment.

Drug: Selective Serotonin Reuptake Inhibitors; Drug: Dextromethorphan

Interventions

Selective Serotonin Reuptake Inhibitors DRUG

Patients in both the study arms will receive SSRI for 8 weeks.

Control group; Test group

Dextromethorphan DRUG

Patients in the test group will get Dextromethorphan 30 mg once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.

Test group

Placebo DRUG

Patients in the control group will get placebo tablet once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.

Control group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with major depressive disorder of either gender within the age group of 18-65 years
• Patients with MADRS score ≥ 7 and ≤ 34 (patients having mild to moderate MDD).
• Patients who are on a stable dose of Sertraline 50 mg or any other Selective Serotonin Reuptake Inhibitor (SSRI) therapy in equivalent dose for less than equal to 4 weeks.
• Patients who have given written informed consent.

You may not qualify if:

• Patients who have been treated with Electro Convulsive Therapy (ECT) recently.
• History of epilepsy, or other major neurological or medical disorders, head trauma.
• Patients with a history of Bipolar Depression (BPD).
• Patients with schizophrenia or other psychotic disorder.
• Patients with suicidal thoughts or risk.
• Patients with cognitive impairment.
• Initiating or stopping formal psychotherapy within six weeks before enrolment.
• Patients with comorbidities like any malignancies, hepatic, renal, cardiovascular,
• neurological or endocrinal, respiratory dysfunction.
• Substance abuse history of psychoactive agents.
• Pregnant and lactating mothers.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (10)

• Wang YT, Wang XL, Feng ST, Chen NH, Wang ZZ, Zhang Y. Novel rapid-acting glutamatergic modulators: Targeting the synaptic plasticity in depression. Pharmacol Res. 2021 Sep;171:105761. doi: 10.1016/j.phrs.2021.105761. Epub 2021 Jul 7.

  PMID: 34242798 RESULT

• Lener MS, Kadriu B, Zarate CA Jr. Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression. Drugs. 2017 Mar;77(4):381-401. doi: 10.1007/s40265-017-0702-8.

  PMID: 28194724 RESULT

• Saavedra JS, Garrett PI, Honeycutt SC, Peterson AM, White JW, Hillhouse TM. Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice. Pharmacol Biochem Behav. 2020 Oct;197:173003. doi: 10.1016/j.pbb.2020.173003. Epub 2020 Aug 2.

  PMID: 32755625 RESULT

• Henter ID, Park LT, Zarate CA Jr. Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. CNS Drugs. 2021 May;35(5):527-543. doi: 10.1007/s40263-021-00816-x. Epub 2021 Apr 26.

  PMID: 33904154 RESULT

• Fogaca MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Mol Psychiatry. 2021 Jul;26(7):3277-3291. doi: 10.1038/s41380-020-00916-y. Epub 2020 Oct 17.

  PMID: 33070149 RESULT

• Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13.

  PMID: 29532791 RESULT

• Nguyen L, Scandinaro AL, Matsumoto RR. Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice. Pharmacol Biochem Behav. 2017 Oct;161:30-37. doi: 10.1016/j.pbb.2017.09.005. Epub 2017 Sep 12.

  PMID: 28916283 RESULT

• Kamijima K, Kimura M, Kuwahara K, Kitayama Y, Tadori Y. Randomized, double-blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder. Psychiatry Clin Neurosci. 2018 Aug;72(8):591-601. doi: 10.1111/pcn.12663. Epub 2018 May 21.

  PMID: 29660207 RESULT

• Maji S, Mishra A, Mohapatra D, Mishra BR, Jena M, Srinivasan A, Maiti R. Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial. Psychiatry Res. 2024 Dec;342:116257. doi: 10.1016/j.psychres.2024.116257. Epub 2024 Nov 8.

  PMID: 39551007 DERIVED

• Maji S, Mohapatra D, Jena M, Srinivasan A, Maiti R. Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol. BMJ Open. 2024 Apr 30;14(4):e080500. doi: 10.1136/bmjopen-2023-080500.

  PMID: 38688675 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Selective Serotonin Reuptake Inhibitors; Dextromethorphan

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Rituparna Maiti, M.D.

  AIIMS, Bhubaneswar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 6, 2022
• Study Start: February 10, 2022
• Primary Completion: September 30, 2023
• Study Completion: November 30, 2023
• Last Updated: December 22, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)