Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

NCT05944510 | Completed Phase 4

• 1 other identifier: AIIMS BBSR/PGThesis/23-24/02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Dextromethorphan acts as N-methyl-D-aspartate (NMDA) antagonist. In Treatment resistant schizophrenia(TRS) the efficacy of treatment response by clozapine is only around 40%. Numerous augmentation agent have been tried which includes antipsychotics, anticonvulsants, antidepressants and NMDA antagonist. The NMDA antagonist such as Riluzole and Memantine have shown good efficacy in TRS. Therefore we are evaluating NMDA antagonist, dextromethorphan in TRS. The dextromethorphan or placebo will be administered along with clozapine in TRS patients. The study is randomized double blind placebo controlled group sequential trial.

Conditions

Treatment Resistant Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Positive and negative symptom scale score

  The change in symptom scoring of schizophrenia at 12 weeks from baseline using Positive and negative symptom scale in the study groups. On this scale, total minimum score= 30, maximum score= 210. Higher score denotes a worse outcome.

  Baseline and 12 weeks

Secondary Outcomes (7)

• Responder rate

  12 weeks

• Incidence of clozapine resistance

  12 weeks

• Requirement of clozapine dose modification

  12 weeks

• Clinical global impression scoring

  12 weeks

• Mini-mental state score

  Baseline and 12 weeks

Study Arms (2)

Add-on Dextromethorphan

EXPERIMENTAL

Dextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.

Drug: Dextromethorphan

Add-on Placebo

PLACEBO COMPARATOR

Matched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.

Drug: Placebo

Interventions

Dextromethorphan DRUG

Dextromethorphan 30mg will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.

Add-on Dextromethorphan

Placebo DRUG

Matched placebo will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.

Add-on Placebo

Eligibility Criteria

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

You may qualify if:

• Schizophrenia patients who are diagnosed as treatment-resistant schizophrenia (TRS) defined as having been tried and not responded to any two antipsychotic medication for a duration of 6 weeks with dose equivalent of 600 mg of chlorpromazine and initiated on clozapine for the treatment of the same.
• The patients who are on stable dose of clozapine.
• Patients of either sex with age \>18 years.
• Patients for whom legally authorized representative (LAR) are willing to give informed consent.

You may not qualify if:

• Patients with significant medical comorbidity.
• Patients with significant psychiatric comorbidity.
• Patients having active substance abuse history during the time of screening.
• Female patients who are pregnant or in reproductive age not using contraception.
• Female patients who are breast feeding

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 (5)

• Siskind D, Siskind V, Kisely S. Clozapine Response Rates among People with Treatment-Resistant Schizophrenia: Data from a Systematic Review and Meta-Analysis. Can J Psychiatry. 2017 Nov;62(11):772-777. doi: 10.1177/0706743717718167. Epub 2017 Jun 28.

  PMID: 28655284 BACKGROUND

• Vayisoglu S, Karahan S, Anil Yagcioglu AE. Augmentation of Antipsychotic Treatment with Memantine in Patients with Schizophrenia: A Systematic Review and Meta-Analysis. Turk Psikiyatri Derg. 2019 Winter;30(4):253-259. English, Turkish.

  PMID: 32594486 BACKGROUND

• Kruse AO, Bustillo JR. Glutamatergic dysfunction in Schizophrenia. Transl Psychiatry. 2022 Dec 3;12(1):500. doi: 10.1038/s41398-022-02253-w.

  PMID: 36463316 BACKGROUND

• de Boer JN, Vingerhoets C, Hirdes M, McAlonan GM, Amelsvoort TV, Zinkstok JR. Efficacy and tolerability of riluzole in psychiatric disorders: A systematic review and preliminary meta-analysis. Psychiatry Res. 2019 Aug;278:294-302. doi: 10.1016/j.psychres.2019.06.020. Epub 2019 Jun 21.

  PMID: 31254879 BACKGROUND

• Siu A, Drachtman R. Dextromethorphan: a review of N-methyl-d-aspartate receptor antagonist in the management of pain. CNS Drug Rev. 2007 Spring;13(1):96-106. doi: 10.1111/j.1527-3458.2007.00006.x.

  PMID: 17461892 BACKGROUND

MeSH Terms

Conditions

Schizophrenia, Treatment-Resistant

Interventions

Dextromethorphan

Condition Hierarchy (Ancestors)

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

• DEBASISH HOTA, D.M.

  AIIMS Bhubaneswar

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: July 13, 2023
• Study Start: August 31, 2023
• Primary Completion: October 15, 2024
• Study Completion: April 30, 2025
• Last Updated: May 9, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)