Poster 10: A Randomized, Controlled Trial of Atomoxetine for Cognitive Dysfunction in Early Huntington's Disease

Abstract

Background Cognitive symptoms are highly associated with functional disability in HD, yet few controlled clinical trials have examined treatments aimed at improving cognition, which could improve patients' levels of independence and quality of life. Methods Atomoxetine is a norepinephrine reuptake inhibitor approved for the treatment of attention deficit/hyperactivity disorder. Twenty participants with mild HD who complained of inattention were given atomoxetine (80 mg) or placebo in a 10-week, double-blind, crossover study. The primary outcome measures were a self-report of attention and an attention and executive neuropsychological composite score. Secondary outcomes were psychiatric and motor symptoms, which were not expected to change. Results Regarding safety and tolerability, the rate of any reported side effects while on atomoxetine was 56% (versus 22% on placebo). The most common side effects were dry mouth (39%), loss of appetite (22%), insomnia (22%), and dizziness (17%). There were no serious adverse events related to atomoxetine. There were statistically significant, mild increases in heart rate and diastolic blood pressure on atomoxetine, consistent with other studies, and these increases did not require medical referral. One participant taking creatine had a mildly elevated creatinine level while on atomoxetine. There were no significant improvements while on atomoxetine compared to placebo on the primary outcomes. However, there was evidence of significant placebo effects. There was a significant improvement in global psychiatric functioning under both treatment conditions. There were no group differences on UHDRS total motor score. Discussion There were small but significant improvements in self-reported attention and psychiatric ratings while on atomoxetine, but there was also a significant placebo effect obscuring efficacy results. There were mild but common side effects that are not ideal in HD, such as dizziness and loss of appetite. Although atomoxetine was not effective at improving attention at this dose, its safety and tolerability were similar to other studies.