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Treatment Resistant SchizophreniaPhase 4NCT05944510

Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

A Phase 4 study testing Dextromethorphan in people with Treatment Resistant Schizophrenia, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Treatment Resistant Schizophrenia
What is being tested?
Dextromethorphan
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteIndia
Study dates
31 Aug 2023to 30 Apr 2025
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

India1 site

  • All India Institute of Medical Sciences (AIIMS)

    Bhubaneswar, Odisha, 751019

Other trials in India

About this study

Official title: 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.

Being tested
Dextromethorphan, Placebo
Medical subject headings
Schizophrenia, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DextromethorphanDrug

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

  • PlaceboDrug

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

Study groups in NCT05944510
Study groupRoleWhat they receive
Add-on DextromethorphanExperimentalDextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.
Receives: Drug: Dextromethorphan
Add-on PlaceboPlacebo comparatorMatched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline and 12 weeks

Secondary outcomes (7)

  1. Responder rate

    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.

    Measured: 12 weeks

  2. Incidence of clozapine resistance

    To evaluate the proportion of patients developing clozapine resistance after 12 weeks of therapy.

    Measured: 12 weeks

  3. Requirement of clozapine dose modification

    To evaluate the proportion of patients requiring clozapine dose increments or decrements over 12 weeks

    Measured: 12 weeks

  4. Clinical global impression scoring

    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.

    Measured: 12 weeks

  5. Mini-mental state score

    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.

    Measured: Baseline and 12 weeks

  6. Serum clozapine level

    To evaluate serum clozapine levels (trough level) at baseline and follow-up at 12 weeks.

    Measured: Baseline and 12 weeks

  7. Incidence of treatment-emergent adverse events

    To evaluate and compare the incidence of treatment-emergent adverse events in both groups.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jul 2023
  2. Study start31 Aug 2023
  3. Primary completion15 Oct 2024
  4. Study completion30 Apr 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05944510
Sponsor's protocol ID
AIIMS BBSR/PGThesis/23-24/02
Status last verified
May 2025
First submitted
6 Jul 2023
Last updated
9 May 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Necessary data can be requested from the principal investigator.

Publications

  • 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.

    PubMed 28655284

  • 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.

    PubMed 32594486

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

    PubMed 36463316

  • 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.

    PubMed 31254879

  • 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.

    PubMed 17461892

  • Hegde NC, Mishra BR, Mohapatra D, Srinivasan A, Maiti R. Augmentation of clozapine with dextromethorphan in treatment-resistant schizophrenia: A randomized, group sequential adaptive design, controlled clinical trial. Asian J Psychiatr. 2026 May;119:104919. doi: 10.1016/j.ajp.2026.104919. Epub 2026 Feb 27.

    PubMed 41780197

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Dextromethorphan in people with Treatment Resistant Schizophrenia, run by All India Institute of Medical Sciences, Bhubaneswar at 1 site in India.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive and negative symptom scale score (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05944510, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2025.

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