This article is more than 5 years old. Information may no longer be current.

Combination dextromethorphan-quinidine well-tolerated, effective for agitation in Alzheimer’s disease

A combination of dextromethorphan-quinidine effectively treated agitation among individuals with probable Alzheimer’s disease, according to study results.

Agitation and aggression are highly prevalent in patients with dementia and are associated with distress for patients and caregivers, greater risk of institutionalization, and accelerated progression to severe dementia and death,” Jeffrey L. Cummings, MD, ScD, of Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, and colleagues wrote. “Nonpharmacological interventions are recommended as first-line therapy, but many patients fail to respond, and pharmacotherapy is often needed. Although many classes of psychotropic drugs are prescribed for agitation, safety concerns and modest or unproven efficacy limit their utility.”

To assess efficacy, safety and tolerability of dextromethorphan-quinidine for Alzheimer’s disease-related agitation, researchers conducted a phase 2, randomized, multicenter, double-blind, placebo-controlled trial in two stages. In the first stage, 220 patients with probable Alzheimer’s disease were randomly assigned 3:4 to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In the second stage, patients receiving dextromethorphan-quinidine continued and those receiving placebo were stratified by response and re-randomized 1:1 to receive dextromethorphan-quinidine (n = 59) or placebo (n = 60). The primary endpoint was change in the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain from baseline.

NPI Agitation/Aggression scores significantly decreased among patients who received dextromethorphan-quinidine compared with those who received placebo (P < .001), according to analysis that combined stage 1 and 2.

In stage 1, mean NPI Agitation/Aggression scores decreased from 7.1 to 3.8 among individuals who received dextromethorphan-quinidine and from 7 to 5.3 among those who received placebo.

In stage 2, NPI Agitation/Aggression scores decreased from 5.8 to 3.8 among those who received dextromethorphan-quinidine and from 6.7 to 5.8 among those who received placebo.

Treatment differences between the dextromethorphan-quinidine and placebo groups were significant in stage 1 (P < .001) and stage 2 (P = .02).

Adverse events included falls, diarrhea and urinary tract infection. Serious adverse events occurred among 7.9% of individuals who received dextromethorphan-quinidine and 4.7% of those who received placebo.

“In this 10-week phase 2 randomized clinical trial of patients with probable Alzheimer's disease, the combination of dextromethorphan-quinidine demonstrated clinically relevant efficacy for agitation and was generally well tolerated. These preliminary findings require confirmation in additional clinical trials with longer treatment duration,” the researchers concluded. – by Amanda Oldt

Disclosure: Cummings reports receiving in-kind research support from Avid Radiopharmaceuticals and Teva Pharmaceuticals, providing consultation to AbbVie, Acadia, ADAMAS, Alzheon, Anavex, AstraZeneca, Avanir, Biogen-Idec, Biotie, Boehringer-Ingelheim, Chase, Eisai, Forum, Genentech, Grifols, Intracellular Therapies, Lilly, Lundbeck, Merck, Neurotrope, Novartis, Nutricia, Otsuka, Pfizer, Prana, QR Pharma, Resverlogix, Roche, Sonexa, Suven, Takeda, and Toyoma companies, and GE Healthcare and MedAvante, owning stock in ADAMAS, Prana, Sonexa, MedAvante, Neurotrax, and Neurokos and owning the copyright of the Neuropsychiatric Inventory. Please see the full study for a list of all authors’ relevant financial disclosures.