title: Effect of armodafinil on cortical activity and working memory in patients with residual excessive sleepiness associated with CPAP-Treated OSA: a multicenter fMRI study.
abstract: OBJECTIVE
  To assess the effect of armodafinil on task-related prefrontal cortex activation using functional magnetic resonance imaging (fMRI) in patients with obstructive sleep apnea (OSA) and excessive sleepiness despite continuous positive airway pressure (CPAP) therapy.
  
  
  METHODS
  This 2-week, multicenter, prospective, randomized, double-blind, placebo-controlled, parallel-group study was conducted at five neuroimaging sites and four collaborating clinical study centers in the United States. Patients were 40 right-handed or ambidextrous men and women aged between 18 and 60 years, with OSA and persistent sleepiness, as determined by multiple sleep latency and Epworth Sleepiness Scale scores, despite effective, stable use of CPAP. Treatment was randomized (1:1) to once-daily armodafinil 200 mg or placebo. The primary efficacy outcome was a change from baseline at week 2 in the volume of activation meeting the predefined threshold in the dorsolateral prefrontal cortex during a 2-back working memory task. The key secondary measure was the change in task response latency.
  
  
  RESULTS
  No significant differences were observed between treatment groups in the primary or key secondary outcomes. Armodafinil was generally well tolerated. The most common adverse events (occurring in more than one patient [5%]) were headache (19%), nasopharyngitis (14%), and diarrhea (10%).
  
  
  CONCLUSIONS
  Armodafinil did not improve fMRI-measured functional brain activation in CPAP-treated patients with OSA and excessive sleepiness.
  
  
  BACKGROUND
  Double-Blind, Placebo-Controlled, Functional Neuroimaging Study of Armodafinil (200 mg/Day) on Prefrontal Cortical Activation in Patients With Residual Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Charlestown, MA.
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Greve
authors.affiliation: Washington University School of Medicine, Department of Neurology, St. Louis, MO.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Duntley
authors.affiliation: Washington University School of Medicine, Department of Radiology, St. Louis, MO.
authors.forename: Linda
authors.initials: L
authors.lastname: Larson-Prior
authors.affiliation: Duke University Medical Center, Durham, NC.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Krystal
authors.affiliation: Duke University Medical Center, Brain Imaging and Analysis Center, Durham, NC.
authors.forename: Michele T
authors.initials: MT
authors.lastname: Diaz
authors.affiliation: University of California and Veterans Affairs San Diego Healthcare System, San Diego, CA.
authors.forename: Sean P A
authors.initials: SP
authors.lastname: Drummond
authors.affiliation: Pacific Research Network, Inc., San Diego, CA.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Thein
authors.affiliation: Stanford School of Medicine, Stanford Sleep Medicine Center, Redwood City, CA.
authors.forename: Clete A
authors.initials: CA
authors.lastname: Kushida
authors.affiliation: Teva Branded Pharmaceutical Products R&D, Inc., Frazer, PA.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Yang
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, MA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D045422:Continuous Positive Airway Pressure / Q000379:methods; D006970:Disorders of Excessive Somnolence / Q000150:complications*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D000077408:Modafinil; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000150:complications* / Q000628:therapy; D016896:Treatment Outcome; D064690:Wakefulness-Promoting Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D064690:Wakefulness-Promoting Agents; D000077408:Modafinil
keywords: 2-back task; Armodafinil; cortical activation; excessive sleepiness; functional magnetic resonance imaging; neuroimaging; obstructive sleep apnea