Distinguishing Treatment Resistance from Comorbidity Burden in Depression Care

EP: 1.Lower Costs, Better Outcomes: Managed Care Strategies for DM-BUP Adoption

EP: 2.From Data to Decisions: Enabling Early Adoption of Cost-Saving Depression Therapies

EP: 3.Reducing Costs for Alzheimer Disease With Better Tolerated Therapies

EP: 4.Leveraging Digital Monitoring for Major Depressive Disorder

EP: 5.Ensuring Timely Access to Next-Line Migraine Therapies

EP: 6.Multidisciplinary Approaches to Optimize Migraine Management

EP: 7.Cost-Effective Strategies for Depression Management at AMCP Nexus

EP: 8.Driving Adoption of Combination Therapies for Treatment-Resistant Depression

EP: 9.The Value of Safer Treatment for Alzheimer Agitation

EP: 10.Expediting Access to DM/BUP for Alzheimer Disease Agitation Management

EP: 11.Leveraging Data to Intervene Early in Treatment-Resistant Depression

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EP: 12.Distinguishing Treatment Resistance from Comorbidity Burden in Depression Care

Steven Stoner, PharmD, a board-certified psychiatric pharmacist and associate dean for student affairs at the University of Missouri–Kansas City, School of Pharmacy, concluded the interview by discussing the potential for the combination product dextromethorphan/bupropion (DM/BUP) to be utilized in other psychiatric populations beyond its current applications in depression and Alzheimer disease agitation.1

Stoner believes that given the drug’s effectiveness demonstrated in treatment-resistant depression and its favorable safety profile in fragile populations, its role may expand. This potential is largely driven by its unique mechanism of action, which involves the NMDA and sigma-1 receptors, moving beyond the conventional focus on monoamines (serotonin, norepinephrine, and dopamine). This novel target broadens the therapeutic possibilities for disorders where traditional monoaminergic approaches have proven inadequate.

The physician noted that the history of psychopharmacology is filled with examples of drugs approved for one indication finding utility in others. For instance, many agents initially approved as antidepressants or second-generation antipsychotics are now widely used for augmentation in mood disorders or for treating anxiety.

Stoner emphasizes that the ability of DM/BUP to offer effective symptom control while avoiding the common and severe side effects of existing therapies—such as the metabolic and movement disorder risks associated with antipsychotics, or the sedation and fall risks associated with benzodiazepines—makes it an attractive candidate for exploration in other psychiatric diagnoses. He asserts that if DM/BUP can demonstrate clinical benefit, its distinct advantages in safety and tolerability should drive its utilization in new populations where the risk-benefit profile of current treatments is unfavorable.

Reference

1. Cutler AJ, Zhao Y, Zeni C, et al. Merative MarketScan cost analysis of patients treated with dextromethorphan-bupropion by treatment line. Presented at: AMCP Nexus; October 27-30, 2025; National Harbor, Maryland. Abstract.