In a preliminary 10-week randomized trial, patients with probable Alzheimer’s disease who took a dextromethorphan-quinidine drug combination had fewer episodes of agitation and lower severity of agitation compared with patients receiving placebo, according to a study published Sept. 22/29 in the Journal of the American Medical Association. Agitation and aggression are common in patients with dementia, and they cause annoyance to patients and their caregivers, pose a greater risk to the foster care system, and accelerate the progression to severe dementia and death. The first line of treatment recommended for these patients is non-pharmacological interventions, but many patients do not respond to this treatment. According to the background information in the article, although many classes of psychiatric drugs can be prescribed for agitation, concerns about drug safety and modest or unproven efficacy limit their use. The combination of dextromethorphan hydrobromide and quinidine sulfate has been approved for the treatment of pseudohypoparasitic affective manifestations (a neurological disorder characterized by affective episodes such as crying), and there is evidence that these medications may provide potential benefit for agitation control. Jeffrey L. Cummings, M.D., Sc.D., of the Cleveland Clinic-Lou Ruvo Center for Brain Health in Las Vegas, and colleagues randomly assigned 220 patients to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127) in phase 1. In phase 2, patients receiving dextromethorphan-quinidine continued the same treatment; those receiving placebo were stratified according to response, and they were reassigned randomly to receive dextromethorphan-quinidine (n = 59) or placebo (n = 60). The 10-week trial was conducted at 42 study sites. A total of 194 patients (88%) completed the study. Analysis of the results of the combined Phase 1 (with all patients) and Phase 2 (again randomly assigned non-responders to placebo) trials showed a significant reduction in the degree of agitation (onset and severity of symptoms) in patients. From baseline status to week 10, patients receiving only dextromethorphan-quinidine had a mean reduction in agitation of 51%. This percentage compared to 26% for those taking placebo only. Adverse events included falls (8.6% in the dextromethorphan-quinidine group versus 3.9% in the placebo group), diarrhea (5.9% in the dextromethorphan-quinidine group versus 3.1% in the placebo group), and urinary tract infections (5.3% in the dextromethorphan-quinidine group versus 3.9% in the placebo group). Serious adverse events were 7.9% in the dextromethorphan-quinidine group and 4.7% in the placebo group. Dextromethorphan-quinidine was not associated with cognitive impairment or sedation. The authors write, “These preliminary results need to be confirmed in more clinical trials with longer treatment durations.” In an accompanying editorial, Anne Corbett, Ph.D., of King’s College London, and colleagues write that while further evidence is pending, there is a fairly strong case for prioritizing dextromethorphan-quinidine as an out-of-indication treatment for bipolar disorder.