Advances in the Management of Major Depressive Disorder - Episode 5

Clinical Experience with Dextromethorphan-bupropion

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The expert psychiatrists share their clinical experience with dextromethorphan-bupropion.


In their clinical practice, the combination of dextromethorphan and bupropion has exceeded their expectations and become one of their most utilized treatments. They attribute this to it being the first oral glutamatergic agent targeting novel mechanisms compared to traditional antidepressants.

Patients tend to notice benefits within 1-2 weeks, consistent with the rapid onset seen in clinical trials. The clinicians ask what patients notice, and common responses are renewed hope, motivation, and ability to enjoy things again—addressing emotional blunting and anhedonia. One patient described feeling lighter, clarifying this meant no longer feeling stuck in her head and looking forward to activities again.

The clinicians agree the agent has a distinct feel compared to other antidepressants and has been broadly effective and well-tolerated. Dizziness is the most common reason for discontinuation. Since bupropion boosts dextromethorphan levels already, caution is warranted if patients are on strong CYP2D6 inhibitor medications or genetically slow metabolizers, with dose lowering often needed.

An example is shared of a trauma psychologist patient doing well on the combo alongside duloxetine. When she tried increasing the dose without guidance, she experienced significant dizziness. This reinforces the importance of close monitoring and dose adjustments if patients are on interacting medications.

In summary, real-world experience reflects clinical trial findings of fast onset and ability to improve anhedonia/blunting. The clinicians emphasize careful dosing, especially around drug interactions, but find the agent to be highly useful for many depression patients.

Summary was AI-generated and edited for clarity.