Advances in the Management of Major Depressive Disorder - Episode 4

Clinical Data with Dextromethorphan-bupropion

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Dr Greg Mattingly reviews the results of GEMINI and ASCEND trials, which led to approval of dextromethorphan-bupropion.


Clinicians discussed two recent studies of the dextromethorphan-bupropion combination agent for depression. The first (GEMINI) showed that the combo was more effective than placebo in reducing depression symptoms over 6 weeks, with separation seen as early as 1 week. This rapid onset supports the theory that it works by enhancing neuroplasticity through glutamate modulation. There were also early signals of functional improvement in areas like work and life enjoyment.

The second study (ASCEND) compared the combo to bupropion alone. Again, there was separation from bupropion starting in the first week, with a 3-fold higher remission rate with the combination at 6 weeks. Despite this greater efficacy, side effect dropout rates were similar between groups. The clinicians note that side effects differ from traditional antidepressants, centering more around dizziness and headaches rather than sexual dysfunction or weight changes, which were not seen.

They note twice daily dosing was used to maintain consistent dextromethorphan levels and smooth out peaks and valleys. If patients are on potent CYP2D6 inhibitor medications already, the dose can be lowered to once daily since those medications already boost dextromethorphan levels. Overall, the early results are promising for a rapid-acting, oral glutamatergic antidepressant with a different side effect profile than traditional agents.

Summary was AI-generated and edited for clarity.