Can Dextromethorphan Be Used in the Treatment of Mood Disorders?

April 17, 2018
Vladimir Maletic

In this occasional feature on Psych Congress Network, members of the Psych Congress Steering Committee answer questions asked by audience members at Psych Congress meetings.

QUESTION: Can Dextromethorphan Be Used in the Treatment of Mood Disorders?

ANSWER: Dextromethorphan (DM) has long been in use as an ingredient in cough medicines. More recently, in combination with quinidine (DM/Q)—added to extend its duration of action by blocking its metabolism via CYP2D6—it has been approved as a treatment for pseudobulbar affect.

Aside from its known impact on opioid transmission, DM has a complex mode of action. Its main activity in mood disorders may be mediated by sigma-1 receptor agonism, inhibition of serotonin and norepinephrine transporters, and noncompetitive antagonism of N-methyl-D-aspartate (NMDA) glutamate receptors.1 It is uncertain if its relatively low affinity for alpha-1 norepinephrine receptors and modulation of nicotinic receptors will have a contribution in the treatment of mood disorders.

Your Questions Answered logoAn open-label proof of concept trial in treatment-resistant major depressive disorder patients showed a demonstrable improvement in depressive symptoms after 10 weeks of adjunct treatment with DM/Q 45/10mg every 12 hours.2 Randomized phase 2 studies evaluating the efficacy of DM/Q in treatment-resistant depression are underway.

Navigating the Maze of Treatment-Resistant Depression

Furthermore, there is some preliminary evidence of benefit from DM/Q in cyclical mood disorders. A retrospective chart review focused on bipolar II and NOS patients in the depressed phase of the illness who did not respond to previous treatment. Patients continued with their previous regimen and received additional DM/Q 20/10mg once or twice a day for 90 days. Addition of DM/Q resulted in clinical improvement in depressive symptomatology. Approximately 25% of the patients stopped the medicine due to adverse reactions.3

Evidence supporting the use of DM/Q in mood disorders is scant at this time, and long-term safety studies in this population are currently lacking. Larger-scale, randomized controlled trials are necessary before one can recommend usage of this medication in mood disorders.

— Vladimir Maletic, MD, MS, Clinical Professor of Psychiatry and Behavioral Science, University of South Carolina School of Medicine, Greenville


1.  Taylor CP, Traynelis SF, Siffert J, Pope LE, Matsumoto RR. Pharmacology of dextromethorphan: relevance to dextromethorphan/quinidine (Nuedexta) clinical use. Pharmacology & Therapeutics. 2016;164:170-182.

2.  Murrough JW, Wade E, Sayed S, et al. Dextromethorphan/quinidine pharmacotherapy in patients with treatment resistant depression: A proof of concept clinical trial. Journal of Affective Disorders. 2017;218:277-283.

3.  Kelly TF, Lieberman DZ. The utility of the combination of dextromethorphan and quinidine in the treatment of bipolar II and bipolar NOS. Journal of Affective Disorders. 2014;167:333-335.


The Role of Inflammation in the Pathophysiology of Schizophrenia

Is There a Place for Cannabidiol in Psychiatric Treatment?

How Stress Impacts Brain-Body Functioning

Can Depression Be Treated With a Daily Baby Aspirin?