(#22) Initiating dextromethorphan 45 mg-bupropion 105 mg (AXS-05) in Patients with Major Depressive Disorder (MDD): Expert Panel Consensus Recommendations

Abstract: Background: In the treatment of MDD, critical needs remain for improved patient outcomes through medications with novel mechanisms of action (MOA). Dextromethorphan 45 mg-bupropion 105 mg (DM-BUP) is a novel, oral, N-methyl-D-aspartate (NMDA) receptor antagonist, sigma-1 receptor agonist, and CYP2D6 inhibitor that was approved for MDD in adults in 2022. To help guide healthcare providers (HCPs) unfamiliar with this compound and its unique MOA, HCPs experienced with prescribing DM-BUP participated in a panel using a modified Delphi process to develop recommendations for initiating (adding or switching) DM-BUP for MDD. Methods: The Chair drafted statements based on clinical experience and literature review. The panel (n=10 HCPs) anonymously voted on the statements and then discussed as a group in 2 rounds of meetings where they were refined and anonymously re-rated the statements which required a pre-specified score threshold to reach consensus. Results: Panelists developed 28 recommendation statements across two topics (1) Overcoming perceived barriers to initiating DM-BUP and (2) Approaches for initiating (adding or switching) DM-BUP for MDD treatment. Consensus was achieved on all items. Key recommendations (paraphrased) included: 1) DM-BUP is a first-line treatment for MDD in target clinical populations; 2) DM-BUP is recommended for those with inadequate response to traditional pharmacological treatments; 3) DM-BUP use is appropriate for individuals with comorbid anxiety; 4) When switching from other treatments, CYP2D6-mediated interactions of both medications must be considered. Conclusions: The recommendations of this panel will provide HCPs with information needed to support treatment decisions in optimizing care for their patients with MDD.Short Description: Dextromethorphan-45mg/bupropion-105mg (AXS-05; DM-BUP) was approved for major depressive disorder (MDD) in 2022. To equip healthcare providers (HCPs) with guidelines on how to initiate (switch/add) DM-BUP in patients, 10 HCPs experienced with prescribing DM-BUP convened to develop recommendations, reaching consensus on 28 statements. Real-world guidelines included using DM-BUP as a first-line treatment and in patients with inadequate response to prior medication, while considering CYP2D6-mediated interactions. These recommendations inform HCP decisions to optimize treatment with DM-BUP.Name of Sponsoring Organization(s): Axsome Therapeutics, Inc.