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Randomized Controlled Trial of Atomoxetine for Cognitive Dysfunction in Early Huntington Disease

Beglinger, Leigh J. PhD*; Adams, Williams H. BA*; Paulson, Henry MD, PhD; Fiedorowicz, Jess G. MD*; Langbehn, Douglas R. MD, PhD*; Duff, Kevin PhD*; Leserman, Anne MSW*; Paulsen, Jane S. PhD*

Journal of Clinical Psychopharmacology: October 2009 - Volume 29 - Issue 5 - p 484-487
doi: 10.1097/JCP.0b013e3181b2ac0a
Brief Reports

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.

From the *Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA; and †Department of Neurology, University of Michigan, Ann Arbor, MI.

Received March 18, 2009; accepted after revision June 12, 2009.

Reprints: Leigh J. Beglinger, PhD, Department of Psychiatry, University of Iowa, MEB 1-321, Iowa City, IA 52242-1000 (e-mail:

Dr Langbehn from the University of Iowa conducted the biostatistical analyses for the study.

This research was supported by an investigator-initiated grant from Eli Lilly and Company.

© 2009 Lippincott Williams & Wilkins, Inc.