Auvelity (Dextromethorphan and Bupropion) | A Fast Acting Antidepressant?

Chris Aiken, MD, reviews the mechanism of action, side effects, and clinical utility of the fast-acting antidepressant Auvelity.

Auvelity (Dextromethorphan and Bupropion) | A Fast Acting Antidepressant? Content written by: Chris Aiken, MD 💡Auvelity Fact Sheet: thecarlatreport.com/auvelity ➡️Full Article: thecarlatreport.com/articles/4417-auvelity-a-fast-acting-ant… 📖Medication Fact Book: thecarlatreport.com/products/499-medication-fact-book-for-ps… ================ Follow Carlat: 🔴SUBSCRIBE ► youtube.com/@thecarlatreport?sub_confirmation=1 ➡️Twitter: / CarlatPsych ================ 00:00 Carlat Intro 00:13 Auvelity 0:46 Mechanism of Action 2:33 Side-effects 2:49 Controversies 3:58 Unanswered Questions 4:18 Carlat Verdict 4:27 Fact Sheet 4:38 TheCarlatReport.com ================ In today’s video, we’re taking a deep dive into Auvelity, a new antidepressant that combines Dextromethorphan and Bupropion. While Bupropion is well-established in the treatment of depression, Dextromethorphan is less familiar in psychiatric contexts. It’s primarily known as a cough suppressant in products like Robitussin DM. The combination in Auvelity aims to offer a new approach by leveraging both drugs’ unique benefits. Auvelity’s primary claim to fame is its dual-action mechanism. Dextromethorphan enhances glutamate transmission through NMDA antagonism, a mechanism seen in other third-line treatments for depression such as ketamine and amantadine. This approach goes beyond traditional monoamines like serotonin and norepinephrine, which are targeted by most antidepressants. Dextromethorphan is also thought to have anti-convulsant and neuroprotective effects and can block serotonin and dopamine reuptake. This novel mechanism makes Auvelity the first oral antidepressant to incorporate this specific approach. The combination of Dextromethorphan and Bupropion in Auvelity helps achieve a pharmacokinetic goal by extending the half-life of Dextromethorphan. Bupropion inhibits CYP2D6, the enzyme responsible for metabolizing Dextromethorphan, thus prolonging its effects from a few hours to over 20. This extended duration might contribute to Auvelity’s effectiveness. Clinical trials provide promising results. Compared to Bupropion alone, Auvelity has shown quicker onset and greater efficacy in treating depression. One large trial, involving over 300 patients, demonstrated that Auvelity effectively improved depressive symptoms faster than other antidepressants. A smaller trial confirmed these findings, noting a significant remission rate of 47% after six weeks, compared to just 16% with Bupropion alone. However, the drug’s effectiveness for treatment-resistant depression is still uncertain, as a large trial in this area yielded negative results. Regarding side effects, Dextromethorphan’s sedative properties can lead to issues such as somnolence, nausea, dizziness, headache, and dry mouth. There is also concern about potential misuse. While the clinical trials showed no inappropriate use, th