Adjunct armodafinil improves wakefulness and memory in obstructive sleep apnea/hypopnea syndrome.

OBJECTIVE: Armodafinil is the R-enantiomer of racemic modafinil and has a significantly longer half-life than the S-enantiomer. This study evaluated armodafinil 150 mg/day as an adjunct treatment for residual excessive sleepiness in patients with obstructive sleep apnea/hypopnea syndrome (OSA/HS) who were otherwise well controlled with nasal continuous positive airway pressure (nCPAP). We assessed the ability of armodafinil to improve wakefulness and cognition and reduce fatigue in this population. METHODS: In this 12-week, randomized, double-blind study, patients (n=259) received armodafinil (150 mg) or placebo once daily. Efficacy assessments at baseline and weeks 4, 8, and 12 included the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Change (CGI-C), Cognitive Drug Research battery, Epworth Sleepiness Scale, and Brief Fatigue Inventory. RESULTS: At final visit, mean (SD) MWT sleep latency increased from baseline by 2.3 (7.8) min with armodafinil and decreased by 1.3 (7.1) min in the placebo group (P=0.0003). Armodafinil improved clinical condition (CGI-C, 71% vs. 53% for armodafinil and placebo, respectively; P=0.0069). Armodafinil significantly improved episodic secondary memory (P=0.0102) and patient-estimated wakefulness (P<0.01) and reduced fatigue (P<0.05) compared with placebo. Armodafinil did not adversely affect nCPAP use. The most common adverse event associated with armodafinil was headache. Sleep macroarchitecture was not altered by armodafinil. CONCLUSION: Adjunct treatment with armodafinil significantly improved alertness, overall clinical condition, and long-term memory. Armodafinil also reduced fatigue and the impact of sleepiness on daily activities in patients with OSA/HS who have residual excessive sleepiness notwithstanding regular use of nCPAP. Armodafinil was well tolerated.

Motor changes in presymptomatic Huntington disease gene carriers.

OBJECTIVE: To determine whether changes in motor function and reaction time are present in presymptomatic individuals carrying the Huntington disease (HD) allele. DESIGN: A case-control, double-blind study comparing asymptomatic at-risk subjects, with or without the HD allele, and subjects clinically determined to have early manifest HD. SETTING: The Department of Medical and Molecular Genetics at Indiana University School of Medicine, Indianapolis. PARTICIPANTS: We studied 383 patients at risk for HD. Each subject was asymptomatic by self-report. MEASURES: Genotype for the HD allele was determined by polymerase chain reaction testing. A battery of 8 physiological tests measuring speed of movement and reaction time was performed with a computer-driven system. RESULTS: Following neurologic examination, 17 of the 120 gene carriers (GCs) had symptoms sufficient for a clinical diagnosis of manifest HD. The remaining 103 GCs were designated presymptomatic GCs. When the non-GCs were compared with the presymptomatic GCs (1-way analysis of covariance and the Fisher protected t test), results on 3 of the 8 physiological tests--movement time, movement time with decision, and auditory reaction time--were different. Additionally, the number of trinucleotide (CAG) repeats significantly correlated with test performance for movement time with decision and visual reaction time with decision when both the entire group of GCs and the presymptomatic GCs alone were considered. CONCLUSION: These results suggest that subtle subclinical changes in motor function are present in presymptomatic individuals who have inherited the HD allele.