Dextromethorphan as an Augmentation Agent in Treatment-resistant Schizophrenia
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.
Timeline
- Start
- 2023-08-31
- Primary completion
- 2024-10-15
- Completion
- 2025-04-30
Outcome
Met primary endpoint
paper The dextromethorphan group significantly outperformed the placebo group in terms of change in total PANSS scores PMID 41780197 ↗
paper Mean difference: -10.68; 95%CI: -18.65, -3.69; p = 0.004 PMID 41780197 ↗
Publications
- Background 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.
- 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.
- Background Kruse AO, Bustillo JR. Glutamatergic dysfunction in Schizophrenia. Transl Psychiatry. 2022 Dec 3;12(1):500. doi: 10.1038/s41398-022-02253-w.
- 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.
- 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.
- 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dextromethorphan | Unknown | 30 mg | — |