Evaluation of dextromethorphan with select antidepressant therapy for the treatment of depression in the acute care psychiatric setting.

Adding dextromethorphan (DXM) to an antidepressant that inhibits CYP2D6 did not speed improvement of depressive symptoms in adults hospitalized for depression. In a retrospective chart review of 40 patients, median time to clinical improvement was 3.00 days for those receiving DXM plus an antidepressant versus 2.83 days for those receiving only an antidepressant, a difference that was not statistically significant. Perceptual disturbances and delusions occurred more often in the DXM group (55% and 35%) than in the control group (30% and 25%). The authors suggest the commonly used 30 mg daily dose may have been too low, and bupropion, the most frequently used antidepressant, has weaker CYP2D6 inhibition than fluoxetine or paroxetine.

Study at a glance

Abstract

Dextromethorphan (DXM), an N-methyl-D-aspartate receptor antagonist, may have ketamine-like antidepressant effects. Dextromethorphan is extensively metabolized via cytochrome P450 (CYP) 2D6, and its half-life in extensive metabolizers is 2 to 4 hours. The purpose of this study was to evaluate the effects of DXM in combination with a moderate-to-strong CYP2D6 inhibitor antidepressant on depression in an acute care psychiatric setting. This was a single-center, retrospective chart review of adult patients with a depressive disorder diagnosis. Patients who received select antidepressant therapy with or without scheduled DXM were included. The primary outcome was the difference in time to improvement of depressive symptoms, which was an average composite of physician documentation, nurse documentation, and first time to 24 hours without as-needed anxiolytics or antipsychotics. The study group consisted of patients who received DXM with select antidepressant therapy, whereas the control group included those who received only select antidepressant therapy. A total of 40 patients were included. The median time to clinical improvement was 3.00 days and 2.83 days for the study group and control group, respectively (P = .986). The incidence of perceptual disturbances and delusions was higher in the study group as compared with the control group (55% and 35% vs 30% and 25%, respectively). Dextromethorphan was not associated with a rapid antidepressant effect. The commonly used dose of 30 mg daily may have been too low to have an effect; additionally, the most frequently utilized select antidepressant, bupropion, has moderately less CYP2D6 inhibition than fluoxetine and paroxetine.