Randomized controlled trial of atomoxetine for cognitive dysfunction in early Huntington disease.
BACKGROUND
Cognitive symptoms are associated with functional disability in Huntington disease; yet, few controlled trials have examined cognitive treatments that could improve patient independence and quality of life. Atomoxetine is a norepinephrine reuptake inhibitor approved for treatment of attention-deficit/hyperactivity disorder.


METHODS
Twenty participants with mild Huntington disease who complained of inattention were randomized to receive atomoxetine (80 mg/d) or placebo in a 10-week double-blind crossover study. Primary outcome measures were self-reported attention and attention and executive neuropsychological composite scores. Secondary outcomes were psychiatric and motor symptom scores.


RESULTS
The rate of reported adverse effects while on atomoxetine was 56% (vs 35% on placebo), which most commonly included 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, although mild, increases in heart rate and diastolic blood pressure on atomoxetine, consistent with other studies and not requiring medical referral. There were no significant improvements while on atomoxetine compared with placebo on primary outcomes. However, there was evidence of significant placebo effects on self-reported attention and psychiatric functions. There were no group differences on the Unified Huntington's Disease Rating total motor score.


CONCLUSIONS
Atomoxetine demonstrated no advantages over placebo for primary or secondary outcomes. Although atomoxetine was not effective at improving attention at this dose, its safety and tolerability were similar to other studies.