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July 06, 2022
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Dextromethorphan-bupropion effective in improving symptoms of major depressive disorder

Dextromethorphan-bupropion significantly improved symptoms for those with major depressive disorder compared with bupropion alone and produced minimal adverse effects, according to a study published in American Journal of Psychiatry.

“Major depressive disorder is a prevalent and disabling condition, and it is the leading cause of disability worldwide,” Herriot Tabuteau, MD, founder and CEO of Axsome Therapeutics, and colleagues wrote. “A tablet (AXS-05) combining dextromethorphan and buproprion has been formulated ... for the treatment of major depression.”

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Tabuteau and fellow researchers aimed to assess safety and efficacy for the AXS-05 formulation to treat major depressive disorder.

The double-blind, multicenter, parallel-group, controlled trial included 80 participants, aged 18 to 65 years with diagnosis of moderate or greater severity of MDD. Participants were randomly assigned on a 1:1 basis to either receive a 45 mg/105 mg tablet of dextromethorphan-buproprion (n = 43) or a 105 mg tablet of sustained-release buproprion (n = 37) once per day for the trial’s initial 3 days, then twice daily thereafter, for a total of 6 weeks.

The study’s primary endpoint was overall treatment effect on Montgomery-Åsberg Depression Rating Scale (MADRS) score (average of the change from baseline for weeks 1 to 6), assessed in all participants who received at least one dose of study medication and had at least one postbaseline assessment.

Results showed the mean change from baseline in MADRS score over weeks 1 to 6 was significantly greater with dextromethorphan-bupropion than with bupropion (13.7 points vs. 8.8 points; least-squares mean difference, 4.9; 95% CI, 3.1 to 6.8). In addition, MADRS score change with dextromethorphan-bupropion was significantly greater than with bupropion at week 2 and every time point thereafter (week 6: 17.3 vs. 12.1 points; least-squares mean difference, 5.2; 95% CI, 1.1 to 9.3).

Response rates (50% decrease in MADRS score from baseline) at week 6 were 60.5% with dextromethorphan-bupropion and 40.5% with bupropion (least-squares mean difference, 19.9%; 95% CI= 1.6 to 41). Data additionally revealed the most common adverse events with dextromethorphan-bupropion were dizziness, nausea, dry mouth, decreased appetite and anxiety, but there were no associations with psychotomimetic effects, weight gain or sexual dysfunction.

“Treatment with dextromethorphan-buproprion resulted in clinically meaningful and statistically significant improvements in depressive symptoms compared with the active comparator buproprion, and was well tolerated,” Tabuteau and colleagues wrote.