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.