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Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia

Phase 4
Completed
Conditions
Treatment Resistant Schizophrenia
Interventions
Registration Number
NCT05944510
Lead Sponsor
All India Institute of Medical Sciences, Bhubaneswar
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Add-on PlaceboPlaceboMatched Placebo will be administered along with clozapine (as standard of care) in Treatment resistant schizophrenia.
Add-on DextromethorphanDextromethorphanDextromethorphan 30mg once daily will be administered along with clozapine (as standard of care) in Treatment-resistant schizophrenia.
Primary Outcome Measures
NameTimeMethod
Positive and negative symptom scale scoreBaseline 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.

Secondary Outcome Measures
NameTimeMethod
Responder rate12 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.

Incidence of clozapine resistance12 weeks

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

Requirement of clozapine dose modification12 weeks

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

Clinical global impression scoring12 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.

Mini-mental state scoreBaseline 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.

Serum clozapine levelBaseline and 12 weeks

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

Incidence of treatment-emergent adverse events12 weeks

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

Trial Locations

Locations (1)

All India Institute of Medical Sciences (AIIMS)

🇮🇳

Bhubaneswar, Odisha, India

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