Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

May 8, 2025 updated by: RITUPARNA MAITI, All India Institute of Medical Sciences, Bhubaneswar

Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia: A Randomized, Group Sequential Adaptive Design, Controlled Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • All India Institute of Medical Sciences (AIIMS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Add-on Placebo
Matched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.
Drug: Placebo
Matched placebo will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.
Experimental: Add-on Dextromethorphan
Dextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.
Drug: Dextromethorphan
Dextromethorphan 30mg will be administered along with Clozapine (standard of care) in treatment resistant schizophrenia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive and negative symptom scale score
Time Frame: Baseline and 12 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of clozapine resistance
Time Frame: 12 weeks
To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy.
12 weeks
Requirement of clozapine dose modification
Time Frame: 12 weeks
To evaluate the proportion of patients requiring clozapine dose increments or decrements over 12 weeks
12 weeks
Serum clozapine level
Time Frame: Baseline and 12 weeks
To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks.
Baseline and 12 weeks
Incidence of treatment-emergent adverse events
Time Frame: 12 weeks
To evaluate and compare the incidence of treatment-emergent adverse events in both groups.
12 weeks
Clinical global impression scoring
Time Frame: 12 weeks
To evaluate for clinical status according to the clinical global impression scale. Clinical global impression is presented in a scale of 1-7. High score denotes a worse outcome.
12 weeks
Mini-mental state score
Time Frame: Baseline and 12 weeks
The change in cognition as assessed by mini-mental state examination on a 30-point questionnaire at 12 weeks from baseline. Minimum and maximum score on this scale is 0 and 30. Lower score denotes worse outcome.
Baseline and 12 weeks
Responder rate
Time Frame: 12 weeks
To analyze and compare responder rate between study groups. The responder rate is defined as ≥ 20% reduction in PANSS score at 12 weeks from baseline.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

All India Institute of Medical Sciences, Bhubaneswar

Investigators

  • Study Chair: DEBASISH HOTA, D.M., AIIMS Bhubaneswar

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2023

Primary Completion (Actual)

October 15, 2024

Study Completion (Actual)

April 30, 2025

Study Registration Dates

First Submitted

July 6, 2023

First Submitted That Met QC Criteria

July 6, 2023

First Posted (Actual)

July 13, 2023

Study Record Updates

Last Update Posted (Actual)

May 9, 2025

Last Update Submitted That Met QC Criteria

May 8, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIIMS BBSR/PGThesis/23-24/02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Necessary data can be requested from the principal investigator.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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