Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial.
James W. Murrough, Elizabeth Wade, Sehrish Sayed, Gabriella Ahle, Drew D. Kiraly, Alison Welch, Katherine A. Collins, Laili Soleimani, Dan V. Iosifescu, Dennis S. Charney
Journal of Affective Disorders August 15, 2017 DOI: 10.1016/j.jad.2017.04.072 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phase IIa open label clinical trial Randomized Placebo-controlled Open-label Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Patients with unipolar treatment-resistant depression |
| Interventions | Dextromethorphan Quinidine |
| Dose | 45/10 mg by mouth every 12h |
| Duration | 10-week period |
| Measures | Montgomery-Asberg Depression Rating Scale (MADRS), QIDS-SR |
| Topics | Depression |
| Keywords | Antidepressant Dextromethorphan Glutamate N-methyl-d-aspartate nmda receptor Treatment resistant |
| Key findings | Dextromethorphan/quinidine up to 45/10 mg twice daily for 10 weeks reduced depression scores and showed acceptable tolerability in patients with treatment-resistant depression. |
Abstract
At least one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD), defined as lack of response to two or more adequate antidepressant trials. For these patients, novel antidepressant treatments are urgently needed. The current study is a phase IIa open label clinical trial examining the efficacy and tolerability of a combination of dextromethorphan (DM) and the CYP2D6 enzyme inhibitor quinidine (Q) in patients with TRD. Dextromethorphan acts as an antagonist at the glutamate N-methyl-d-aspartate (NMDA) receptor, in addition to other pharmacodynamics properties that include activity at sigma-1 receptors. Twenty patients with unipolar TRD who completed informed consent and met all eligibility criteria we enrolled in an open-label study of DM/Q up to 45/10mg by mouth administered every 12h over the course of a 10-week period, and constitute the intention to treat (ITT) sample. Six patients discontinued prior to study completion. There was no treatment-emergent suicidal ideation, psychotomimetic or dissociative symptoms. Montgomery-Asberg Depression Rating Scale (MADRS) score was reduced from baseline to the 10-week primary outcome (mean change: -13.0±11.5, t19=5.0, p<0.001), as was QIDS-SR score (mean change: -5.9±6.6, t19=4.0, p<0.001). The response and remission rates in the ITT sample were 45% and 35%, respectively. Open-label, proof-of-concept design. Herein we report acceptable tolerability and preliminary efficacy of DM/Q up to 45/10mg administered every 12h in patients with TRD. Future larger placebo controlled randomized trials in this population are warranted.
Comparable studies
Other non-randomized and open-label trials on depression, most cited first.
Citations in the library
Cited by 22
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Psychedelics, placebo effects, and set and setting: Insights from common factors theory of psychotherapy Transcultural Psychiatry January 26, 2021
- Novel drug developmental strategies for treatment‐resistant depression British Journal of Pharmacology November 25, 2021
- Glutamatergic Modulators in Depression Harvard Review of Psychiatry February 21, 2018
- Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS Drugs November 1, 2024
and 17 more in the library
Cites 8
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
and 3 more in the library