Cough Medicine for Depression?

Yes, cough medicine!

This blog entry touches upon the same issue that was detailed in the “What’s In a Name...” blog entry of November 2020. Medications are "born” with a certain designation, which then follows them throughout their lives as they acquire new and new indications. That is why we use blood pressure medications for nightmares, antidepressants for panic attacks, seizure medications for bipolar disorder, and so on. So don’t be surprised if your next antidepressant is a cough medicine.

Dextromethorphan (DXM), the active ingredient in over-the-counter products like Delsym, Mucinex or Coricidin, is a promising new antidepressant. It is not surprising, if we consider that its effect in the brain mimics that of ketamine – it hits many of the same receptors, albeit in a weaker fashion.

In addition to it being a “week ketamine”, it also gets eliminated very quickly by the liver, so in order for it to linger around long enough to exert any meaningful effect in the brain, its breakdown has to be blocked in the liver. 

The drug that came to the market uses Wellbutrin (bupropion) for that purpose. It is known to be strong inhibitor of the enzyme called CYP 2D6, which breaks down DXM in the liver. Inhibiting the activity of this enzyme extends the presence of DXM from 1 hour to up to 8 or 10, allowing it to exert its effect long enough to be noticeble by the brain.

But Wellbutrin itself is already an antidepressant, how do you know that the effect is not due to it? 

Many people ponder about the same, but what seems to be be unique about this combination is that the antidepressant effect becomes noticeable within a week, and that is clearly not due to the Wellbutrin, which takes 3 - 4 weeks to start producing noticeable improvement in mood, like all other traditional antidepressants. That early response is likely due to the ketamine-like effect of dextromethorphan. 

The FDA approved the single-tablet combination of bupropion and DXM as Auvelity in August of 2022. The experience has been positive so far!

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Alexander Papp, MD