Dextromethorphan/bupropion in major depressive disorder: a profile of its use

Plain Language SummaryMajor depressive disorder (MDD) is one of the most common mental health conditions in the world and poses a serious public health problem. Some patients do not respond to conventional antidepressants, prompting the need for new treatments that are effective and fast-acting. A fixed-dose combination tablet containing dextromethorphan and bupropion (AUVELITY(& REG;)) has been approved for the treatment of MDD in adults. Evidence for the efficacy of dextromethorphan/bupropion has been demonstrated in clinical trials in patients with MDD, where it rapidly improved depressive symptoms compared with placebo or sustained-release (SR) bupropion within 1-2 weeks. Dextromethorphan/bupropion also improved remission rates compared with placebo or bupropion SR. The benefits of dextromethorphan/bupropion were maintained during longer term treatment. Dextromethorphan/bupropion was generally well tolerated; the most common adverse events were dizziness and nausea. Given its efficacy and tolerability profile, dextromethorphan/bupropion is a useful treatment option for adults with MDD. Dextromethorphan/bupropion (AUVELITY(& REG;)), an oral, fixed-dose combination of dextromethorphan hydrobromide and bupropion hydrochloride, is a useful treatment option for adults with major depressive disorder (MDD). Dextromethorphan is an uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist. The antidepressant bupropion (an aminoketone and cytochrome P450 2D6 inhibitor) increases the bioavailability of dextromethorphan. In randomized, double-blind, clinical trials in patients with MDD, dextromethorphan/bupropion demonstrated early, clinically meaningful improvements in depressive symptoms, remission rates, and functional disability compared with placebo or sustained-release (SR) bupropion, with these improvements sustained over the longer term. Dextromethorphan/bupropion was generally well tolerated, including in the long term, and was not associated with a signal for increased psychotomimetic effects, weight gain, or increased suicidal behaviors.