Patients with major depressive disorder (MDD) who take a combination of dextromethorphan and bupropion may experience greater symptom improvements than those taking bupropion alone, suggests a small study published Wednesday in the American Journal of Psychiatry. The study was funded by Axsome Therapeutics, which is developing an oral formulation of dextromethorphan and bupropion.
“This study is the first controlled trial of dextromethorphan-bupropion in patients with depression,” wrote Herriot Tabuteau, M.D., of Axsome Therapeutics Inc. and colleagues. “[T]reatment with dextromethorphan-bupropion resulted in clinically meaningful and statistically significant improvements in depressive symptoms compared with the active comparator bupropion, and was well tolerated.”
Tabuteau and colleagues analyzed data from a six-week, randomized, double-blind phase 2 trial including 80 participants aged 18 to 65 years. All participants had a confirmed MDD diagnosis and were experiencing a major depressive episode of moderate or greater severity. They were randomly assigned to receive either dextromethorphan-bupropion (45 mg/105 mg tablet) or bupropion (105 mg tablet) once daily for the first three days of the trial, and twice daily for the remainder of the six-week trial.
Depression severity was defined as participants’ ratings on the Montgomery-Åsberg Depression Rating Scale (MADRS), with higher scores representing more severe depression. MADRS was completed at baseline and at weeks one, two, three, four, and six. Clinical response was defined as a reduction of at least 50% from baseline in MADRS score, while remission was defined as a MADRS score of 10 or less.
Participants treated with dextromethorphan-bupropion were significantly more likely to experience a reduction in their MADRS scores between baseline and six weeks compared with those who received bupropion. By the end of the trial, participants in the dextromethorphan-bupropion group had an average reduction of 17.3 points on the MADRS scale, compared with 12.1 points for those in the bupropion group. Further, 46.5% of participants in the dextromethorphan-bupropion group entered remission by the end of the study, compared with 16.2% in the bupropion group. Finally, 60.5% of those in the dextromethorphan-bupropion group achieved a clinical response by the end of the study, compared with 40.5% in the bupropion group.
In the dextromethorphan-bupropion group, 72.9% of participants reported adverse events, such as dizziness, nausea, and anxiety, compared with 64.6% in the bupropion group. The majority of adverse events were mild or moderate, and no serious adverse events, such as hospitalizations, occurred.
“Dextromethorphan-bupropion rapidly reduced depressive symptoms, as measured by the MADRS total score, as early as week 1, with statistically significant differences over bupropion observed by week 2 and at every time point thereafter,” the authors wrote.
For related information, see the Psychiatric News article “Bupropion May Be Best for Overweight Patients With Depression.”
(Image: iStock/vadimguzhva)
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