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First and Only Oral NDMA Receptor Antagonist for MDD Can Now Be Prescribed
Extended-release dextromethorphan HBr-bupropion HCl (Auvelity™), the only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of major depressive disorder (MDD), is now available by prescription in the United States, maker Axsome Therapeutics Inc. announced.
“Auvelity™ utilizes the first new oral non-monoamine-based mechanism of action in more than 6 decades approved for the treatment of major depressive disorder in adults,” Psych Congress Steering Committee Member Rakesh Jain, MPH, said in the news release. “Based on its demonstrated rapid action starting at 1 week versus placebo, and its sustained effect, Auvelity™ represents an important new treatment for patients suffering from this debilitating and potentially life-threatening condition.”
Related: FDA Approves First Oral NMDA Receptor Antagonist for MDD in Adults
In addition to containing an NDMA receptor antagonist, dextromethorphan HBr-bupropion HCl consists of bupropion (105-mg), an aminoketone and CYP2D6 inhibitor “which serves to increase and prolong the blood levels of dextromethorphan,” the company said in the news release. The drug is supplied in 105-mg tablets in 30-count bottles.
On August 18th, 2022, the US Food and Drug Administration (FDA) approved dextromethorphan HBr-bupropion HCl extended-release tablets 45mg/105mg after previously granting Breakthrough Therapy Designation in March 2019.
The Breakthrough Therapy designation process expedites the development and review of drugs to treat serious conditions. To receive this designation, a drug must show an advantage and improvement over available therapy.
The efficacy of dextromethorphan HBr-bupropion HCl was demonstrated in both the GEMINI placebo-controlled trial and through confirmatory evidence in the ASCEND study, encompassing 1100 patients with depression.
In the GEMINI study, dextromethorphan HBr-bupropion HCl was “significantly superior” to placebo for improving depressive symptoms at week 6 measured by the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Additionally, compared with placebo, changes in MADRS total score from baseline to week 1 and week 2 were significantly better with dextromethorphan HBr-bupropion HCl. The most common adverse reactions to the drug were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis, the study found.
In ASCEND, dextromethorphan HBr-bupropion HCl was significantly superior to bupropion sustained-release tablets 105-mg twice daily on the study’s primary measure, which assessed change from baseline in MADRS total scores from week 1 to week 6 and then averaged the scores.
Related: FDA Grants Fast Track Designation to Novel MDD Monotherapy
Auvelity™ comes with a Black Box Warning for increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. The drug is not approved for use in children,[BM2] as it is unknown if it is safe and effective in that population.
When prescribing patients HBr-bupropion HCl, clinicians should do some of the following:
- Assess blood pressure before treatment with periodic assessments during treatment
- Screen patients for a personal or family history of bipolar disorder, mania, or hypomania
- Determine whether a patient is receiving any other medications containing bupropion or dextromethorphan
“Auvelity™ may shift the way physicians approach the treatment of patients experiencing major depressive disorder due to its differentiated clinical profile,” said Dr Jain who is also a clinical professor in the Department of Psychiatry at Texas Tech University School of Medicine, Austin.
References
Psych Congress Network news articles are not medical advice.
