Dextromethorphan-Bupropion in Major Depressive Disorder: Controlled Trial
The combination is known as AXS-05 in studies and will be marketed as Auvelity.<p>Interesting combo. Buproprion is an antidepressant by itself, but it also inhibits the enzymes that break Dextromethorphan down in the body. Taking the two drugs together is not equivalent to taking the same dose of Dextromethorphan alone because Bupropion induces a very different exposure to DXM and its metabolites. Ignore anyone who tries to compare this to recreational DXM consumption because they&#x27;re quite different.<p>Dextromethorphan gets a lot of attention for being an NMDA antagonist, but fewer people know that it has quite strong affinity for the serotonin transporter (the primary affinity of SSRIs). It also has potentially significant affinity for the sigma-1 receptor, the norepinephrine transporter, and several other receptors that have been noted to be potentially useful for depression modulation.<p>In other words, this feels a little bit like a shotgun approach to poking a wide array of receptors that may or may not be helpful in modulating depressive disorders. I&#x27;d take some of the narratives about this being an &quot;NMDA drug like ketamine&quot; with a huuuge grain of salt.<p>People have been trying this combination for several years in DIY fashion (not recommended, but info is out there) since the original study came out. I&#x27;ve seen some reports of good results, other reports of weird side effects that interfered with daily activities. I wouldn&#x27;t rush to characterize this as a miracle drug or a first-line treatment, but it does seem to help certain patients who haven&#x27;t seen much benefit from previous drugs.<p>Also worth noting that other studies haven&#x27;t been as overwhelmingly positive as this one. Axsome Therapeutics (company researching the drug) stumbled a few years ago when their own trial failed to show statistical significance for Bupropion+DXM over Bupropion alone. Later studies seem to have been more positive though.