A Pilot Study to Evaluate the Efficacy of Dextromethorphan/Quinidine in Treating Irritability in Huntington's Disease
Erin Furr-Stimming1, Shayan Zadegan2, Jorge Patino Murillas3, Deepa Dongarwar3, Natalia Pessoa Rocha4
1University of Texas Health Science Center-Houston, 2The University of Texas Health Science Center at Houston (UTHealth), 3The University of Texas Health Science Center at Houston McGovern Medical School, 4UTHealth Houston
Objective:
To prove the efficacy and safety of dextromethorphan/quinidine 20mg/10mg in patients with irritability due to HD.
Background:
Irritability is one of most common neuropsychiatric symptoms in HD, often leading to aggressive behavior with severe consequences. No medications are approved to treat specifically irritability in HD, and the available treatments are off–label and imperfect. We hypothesize that dextromethorphan/quinidine (Nuedexta®) would decrease irritability in individuals with HD and minimize aggression and outbursts.
Design/Methods:
Randomized, double-blind, placebo-controlled, crossover, proof of concept study with 20 adults with verified HD mutation and irritability [defined as an Irritability Scale (IS) score > 14]. Primary outcomes: improvement of irritability, described as a 4-point change from baseline in the IS. Secondary outcomes: Irritability, as quantified by the changes in the total IS score; Change of behavioral symptoms (UHDRS, HADS, PBA-s, NPI - Q); Change in the motor symptoms (TMS); Change in functional independence (TFC).
Results:
Eighteen individuals completed the trial. Compared to baseline, we observed a significant reduction in the IS score with both placebo (mean decrease of 7.6 points, 27.5%) and dextromethorphan/quinidine (mean reduction of 8.8 points, or 32%) treatments. The results were similar when we analyzed the irritability/aggression score of the PBA-s. We did not find differences when comparing placebo and dextromethorphan/quinidine treatments. In addition, we did not find differences between treatments for any of the secondary outcomes.
Conclusions:
Although we observed a pronounced decrease in the IS score after the treatment with dextromethorphan/quinidine, our study revealed a strong placebo effect, and there was no difference between treatments.