Monday, August 22, 2022

FDA Approves Novel Rapid-Acting Oral Antidepressant

The Food and Drug Administration (FDA) has approved Auvelity, an extended-release tablet that combines dextromethorphan and bupropion for the treatment of major depressive disorder in adults. The FDA granted Breakthrough Therapy designation to Auvelity in March 2019.

Dextromethorphan, commonly used as a cough suppressant, inhibits the NMDA receptor, which is the same receptor targeted by the rapid-acting antidepressant esketamine. The antidepressant bupropion inhibits the metabolic enzyme CYP2D6, which prolongs the time that dextromethorphan remains active.

“The approval of Auvelity represents a milestone in depression treatment based on its novel oral NMDA antagonist mechanism, its rapid antidepressant efficacy demonstrated in controlled trials, and a relatively favorable safety profile,” said Maurizio Fava, M.D., psychiatrist-in-chief at Massachusetts General Hospital and the Slater Family Professor of Psychiatry at Harvard Medical School, in a press release from Axsome Therapeutics, manufacturer of Auvelity.

The approval of Auvelity was based on two large clinical trials. The first was a placebo-controlled trial known as GEMINI, which included 327 adults with major depression. After six weeks, Montgomery-├ůsberg Depression Rating Scale (MADRS) scores dropped by 16 points among adults randomized to twice-daily Auvelity (45 mg dextromethorphan and 105 mg bupropion) compared with 12 points of those randomized to placebo. In addition, 40% of adults taking Auvelity achieved remission (defined as MADRS score of ≤ 10) compared with 17% of those taking placebo.

The second trial, called ASCEND, involved 97 adults with major depression and compared the 45 mg dextromethorphan/105 mg bupropion combo with 105 mg bupropion alone. Like the GEMINI trial, adults taking Auvelity showed greater reductions in MADRS scores after six weeks than those taking bupropion (13.7 points vs. 8.8 points, respectively) and greater remission rates (47% vs 16%). The most common side effects included dizziness, headache, diarrhea, sleepiness, dry mouth, sexual dysfunction, and excessive sweating.

In its release, Axsome said that Auvelity is expected to be commercially available by the end of this year.

For related information, see “Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial.”