Clinical trial NCT05944510: Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
Official title: Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia: A Randomized, Group Sequential Adaptive Design, Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Treatment Resistant Schizophrenia
Lead sponsor: All India Institute of Medical Sciences, Bhubaneswar
Sponsor class: OTHER
First posted: 2023-07-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Positive and negative symptom scale score
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Responder rate
timeFrame: 12 weeks
measure: Incidence of clozapine resistance
timeFrame: 12 weeks
measure: Requirement of clozapine dose modification
timeFrame: 12 weeks
measure: Clinical global impression scoring
timeFrame: 12 weeks
measure: Mini-mental state score
timeFrame: Baseline and 12 weeks
measure: Serum clozapine level
timeFrame: Baseline and 12 weeks
measure: Incidence of treatment-emergent adverse events
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Bhubaneswar
country: India
facility: All India Institute of Medical Sciences (AIIMS)
state: Odisha
Study officials:
affiliation: AIIMS Bhubaneswar
name: DEBASISH HOTA, D.M.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: Kruse AO, Bustillo JR. Glutamatergic dysfunction in Schizophrenia. Transl Psychiatry. 2022 Dec 3;12(1):500. doi: 10.1038/s41398-022-02253-w.
citation: 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.
citation: 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.