Expediting Access to DM/BUP for Alzheimer Disease Agitation Management

Steven Stoner, PharmD, a board-certified psychiatric pharmacist and associate dean for student affairs at the University of Missouri–Kansas City, School of Pharmacy, discussed strategies for managed care organizations (MCOs) and providers to ensure rapid patient access to dextromethorphan-bupropion (DM/BUP) once approved for Alzheimer disease (AD)-related agitation.¹ Given the high prevalence of agitation and the scarcity of well-tolerated treatment options, quick access is paramount.

Stoner's primary recommendation centers on 2 core activities:

1. Formulary Review: MCOs must initiate the formal process of reviewing and adding DM/BUP to their formularies early
2. Provider Education: Providers need to become comfortable with this new treatment, especially in a fragile patient population. While most are familiar with bupropion, the combination and its specific application for AD agitation are novel. Education must cover the drug's proposed mechanism of action, its favorable safety and tolerability profile compared to existing therapies (like antipsychotics), and its effectiveness in controlling agitation without over-sedation

A crucial point raised for provider comfort involves avoiding known contraindications. Stoner cited the concern with using bupropion in patients with eating disorders due to seizure risk. In AD, where wasting is common, providers should be educated on which patients are most suitable for the combination.

Finally, Stoner addressed the potential for DM/BUP to delay or prevent facility placement and emergency interventions. He explained that one of the main drivers for institutionalization is when caregivers can no longer safely manage a loved one's aggressiveness, irritability, or agitation at home. If DM/BUP can effectively calm the individual without over-sedation or exacerbating cognitive decline, it allows patients to remain in their residential setting longer. Successfully managing these episodes in the ambulatory care setting directly contributes to delaying facility placement, offering significant quality of life and cost benefits.

Reference

1. Cummings J, Grossberg, Streicher C, DePue R, Tabuteau H. Efficacy and safety of AXS-05 in Alzheimer's disease agitation: a phase 3 randomized withdrawal double-blind placebo-controlled study. Presented at: AMCP Nexus; October 27-30, 2025; National Harbor, Maryland. Abstract. (Study 2)