Repurposing of Dextromethorphan as an Adjunct Therapy in Patients With Major Depressive Disorder
NCT ID: NCT05181527
Last Updated: 2023-12-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE4
60 participants
INTERVENTIONAL
2022-02-10
2023-11-30
Brief Summary
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Detailed Description
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Another major concern is the therapeutic lag period with all of these monoaminergic antidepressants. Additionally, most of the available antidepressant drugs have many adverse effects, which increase with increments in dose. The discovery of the rapid and sustained antidepressant effect of subanesthetic dose of ketamine, especially in the treatment of non-responders and treatment-resistant cases leads to many extensive clinical and preclinical research in the recent past. As repeated doses of ketamine are related to abusive potential and many other adverse effects, the search for a similar antidepressant agent is going on, which acts via a similar mechanism with a better safety profile. Dextromethorphan, an FDA-approved over-the-counter antitussive drug, has a similar property of non-competitively blocking N-methyl-D-aspartate receptors of glutamate, like ketamine. Additionally, Dextromethorphan has serotonin transporter inhibitory and NET inhibitory properties, so it can also increase the availability of serotonin in synapses, hence may achieve a synergistic effect with SSRIs. In 2010, US-FDA approved Dextromethorphan plus quinidine (Nuedexta) for use in pseudobulbar affect (PBA), and currently, it is under investigation as a potential antidepressant agent in MDD (NCT01882829, NCT02153502). In the phase, IIa clinical trial by Murrough et al. have reported acceptable tolerability and efficacy of dextromethorphan/quinidine combination in treatment-resistant depression (TRD). Another combination of Dextromethorphan and bupropion is currently in phase III clinical trial for TRD. In the present background, the investigators hypothesize that the major concerns of antidepressant therapy like therapeutic latency, lack of efficacy, and adverse drug reactions may be overcome by adding Dextromethorphan to SSRI in MDD. As SSRIs inhibit CYP2D6, the addition of quinidine with Dextromethorphan may not be reasonable and hence, not considered in the present study. The literature search found that to date, there is no randomized controlled trial on Dextromethorphan as an add-on therapy to first-line antidepressants like SSRIs. So, the present randomized controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to SSRIs in major depressive disorder.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Control group
Patients in the control group will get an identical-looking capsule containing placebo (starch) once daily in addition to SSRI.
Selective Serotonin Reuptake Inhibitors
Patients in both the study arms will receive SSRI for 8 weeks.
Placebo
Patients in the control group will get placebo tablet once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.
Test group
Patients in the test group will get Dextromethorphan 30 mg once daily orally as an add-on to ongoing SSRI treatment.
Selective Serotonin Reuptake Inhibitors
Patients in both the study arms will receive SSRI for 8 weeks.
Dextromethorphan
Patients in the test group will get Dextromethorphan 30 mg once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.
Interventions
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Selective Serotonin Reuptake Inhibitors
Patients in both the study arms will receive SSRI for 8 weeks.
Dextromethorphan
Patients in the test group will get Dextromethorphan 30 mg once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.
Placebo
Patients in the control group will get placebo tablet once daily orally as an add-on to ongoing SSRI treatment for 8 weeks.
Eligibility Criteria
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Inclusion Criteria
* Patients with MADRS score ≥ 7 and ≤ 34 (patients having mild to moderate MDD).
* Patients who are on a stable dose of Sertraline 50 mg or any other Selective Serotonin Reuptake Inhibitor (SSRI) therapy in equivalent dose for less than equal to 4 weeks.
* Patients who have given written informed consent.
Exclusion Criteria
* History of epilepsy, or other major neurological or medical disorders, head trauma.
* Patients with a history of Bipolar Depression (BPD).
* Patients with schizophrenia or other psychotic disorder.
* Patients with suicidal thoughts or risk.
* Patients with cognitive impairment.
* Initiating or stopping formal psychotherapy within six weeks before enrolment.
* Patients with comorbidities like any malignancies, hepatic, renal, cardiovascular,
* neurological or endocrinal, respiratory dysfunction.
* Substance abuse history of psychoactive agents.
* Pregnant and lactating mothers.
18 Years
65 Years
ALL
No
Sponsors
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All India Institute of Medical Sciences, Bhubaneswar
OTHER
Responsible Party
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RITUPARNA MAITI
Professor
Principal Investigators
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Rituparna Maiti, M.D.
Role: PRINCIPAL_INVESTIGATOR
AIIMS, Bhubaneswar
Locations
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All India Institute of Medical Sciences (AIIMS)
Bhubaneswar, Odisha, India
Countries
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References
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Wang YT, Wang XL, Feng ST, Chen NH, Wang ZZ, Zhang Y. Novel rapid-acting glutamatergic modulators: Targeting the synaptic plasticity in depression. Pharmacol Res. 2021 Sep;171:105761. doi: 10.1016/j.phrs.2021.105761. Epub 2021 Jul 7.
Lener MS, Kadriu B, Zarate CA Jr. Ketamine and Beyond: Investigations into the Potential of Glutamatergic Agents to Treat Depression. Drugs. 2017 Mar;77(4):381-401. doi: 10.1007/s40265-017-0702-8.
Saavedra JS, Garrett PI, Honeycutt SC, Peterson AM, White JW, Hillhouse TM. Assessment of the rapid and sustained antidepressant-like effects of dextromethorphan in mice. Pharmacol Biochem Behav. 2020 Oct;197:173003. doi: 10.1016/j.pbb.2020.173003. Epub 2020 Aug 2.
Henter ID, Park LT, Zarate CA Jr. Novel Glutamatergic Modulators for the Treatment of Mood Disorders: Current Status. CNS Drugs. 2021 May;35(5):527-543. doi: 10.1007/s40263-021-00816-x. Epub 2021 Apr 26.
Fogaca MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Mol Psychiatry. 2021 Jul;26(7):3277-3291. doi: 10.1038/s41380-020-00916-y. Epub 2020 Oct 17.
Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13.
Nguyen L, Scandinaro AL, Matsumoto RR. Deuterated (d6)-dextromethorphan elicits antidepressant-like effects in mice. Pharmacol Biochem Behav. 2017 Oct;161:30-37. doi: 10.1016/j.pbb.2017.09.005. Epub 2017 Sep 12.
Kamijima K, Kimura M, Kuwahara K, Kitayama Y, Tadori Y. Randomized, double-blind comparison of aripiprazole/sertraline combination and placebo/sertraline combination in patients with major depressive disorder. Psychiatry Clin Neurosci. 2018 Aug;72(8):591-601. doi: 10.1111/pcn.12663. Epub 2018 May 21.
Maji S, Mishra A, Mohapatra D, Mishra BR, Jena M, Srinivasan A, Maiti R. Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial. Psychiatry Res. 2024 Dec;342:116257. doi: 10.1016/j.psychres.2024.116257. Epub 2024 Nov 8.
Maji S, Mohapatra D, Jena M, Srinivasan A, Maiti R. Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol. BMJ Open. 2024 Apr 30;14(4):e080500. doi: 10.1136/bmjopen-2023-080500.
Other Identifiers
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AIIMSBBSR/PGThesis/21-22/74
Identifier Type: -
Identifier Source: org_study_id