The Value of Safer Treatment for Alzheimer Agitation

Steven Stoner, PharmD, a board-certified psychiatric pharmacist and associate dean for student affairs at the University of Missouri–Kansas City, School of Pharmacy, commented on a study presented at AMCP Nexus concerning the value of dextromethorphan-bupropion (DM/BUP) in managing agitation in patients with Alzheimer disease (AD).¹ The study highlighted that DM/BUP showed no signs of sedation or cognitive decline and had zero discontinuations due to side effects—a critically important finding in this vulnerable patient population.

Stoner explains that AD-related agitation not only places a tremendous burden on the individual but also on caregivers, frequently leading to the high cost of nursing care placement. The therapeutic goal is to achieve calmness without over-sedation, preserving patient function and avoiding the use of tranquilization.

The core of DM/BUP’s cost-effectiveness lies in its superior safety profile compared to existing treatments. Traditional therapies, primarily antipsychotics, carry significant risks in older adults, including drug-induced movements, metabolic issues, and a mandated increased risk of death warning. Alternatively, benzodiazepines increase the risk of fall-related injuries, over-sedation, and dizziness—all known drivers of high-cost emergency room visits and hospitalizations.

Stoner argues that MCOs must update their cost-effectiveness models to directly account for these avoided costs. Every aggressive outburst requires staff intervention, and every adverse drug event (like a fall or the development of metabolic syndrome) incurs substantial healthcare expenses. By using an agent that effectively manages agitation, avoids cognitive worsening, and minimizes these severe side effects, MCOs can realize significant savings in both direct and indirect costs. This favorable tolerability profile provides a compelling financial and clinical argument for the drug's role in AD management.

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)