Assessing the efficacy of dextromethorphan/quinidine in treating irritability in Huntington's disease

BackgroundHuntington's disease (HD) is a neurodegenerative disorder caused characterized by motor, cognitive, and psychiatric/behavioral impairments. Among these symptoms, irritability is particularly burdensome due to its frequency and significant impact on the daily lives of both patients and caregivers. Currently, no FDA-approved medication specifically targets this symptom.ObjectiveTo assess the efficacy of dextromethorphan/quinidine (DM/Q) 20/10 mg (NUEDEXTA^®) in managing irritability in HD.MethodsDouble-blind, placebo-controlled, randomized, crossover clinical trial. Participants underwent a 13-week study: six weeks of DM/Q treatment, one-week washout, and six weeks of placebo. The DM/Q 20/10 mg regimen started with a once-daily dose, increased to twice daily after the first week, and tapered back to once daily in the sixth week. Participants were evaluated during three in-person visits: at baseline and at the end of each treatment phase. Assessments included motor and cognitive exams, the Irritability Scale, and the Problem Behavior Assessment-short version (PBA-s) (ClinicalTrials.gov NCT03854019).ResultsTwenty participants were enrolled, with 18 completing the study (mean age = 43.94 ± 10.70 years, 11 females and 7 males). Both DM/Q and placebo reduced mean Irritability Scale scores (32% and 27.5%, respectively) and the irritability subscale of the PBA-s (42% and 33%, respectively), with no statistically significant differences between groups. Additionally, DM/Q showed no significant advantage over placebo in motor, behavioral, or cognitive outcomes.ConclusionDM/Q did not demonstrate significant benefits in managing irritability compared to placebo. Further research with larger sample sizes and alternative therapeutic strategies is needed to effectively address this symptom in HD.