title: Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal.
abstract: OBJECTIVE
  We examined the changes in waking electroencephalography (EEG) biomarkers with modafinil during continuous positive airway pressure (CPAP) withdrawal in patients with obstructive sleep apnea (OSA) to investigate neurophysiological evidence for potential neurocognitive improvements.
  
  
  METHODS
  Randomized double-blind placebo-controlled crossover study. CPAP was used for the first night and then withdrawn for 2 subsequent nights. Each morning after the 2 CPAP withdrawal nights, patients received either 200 mg modafinil or placebo. After a 5-w washout, the procedure repeated with the crossover drug.
  
  
  METHODS
  University teaching hospital.
  
  
  METHODS
  Stable CPAP users (n = 23 men with OSA).
  
  
  RESULTS
  Karolinska Drowsiness Test (KDT) (awake EEG measurement with eyes open and closed), Psychomotor Vigilance Task (PVT), and driving simulator Performance were assessed bihourly during the 3 testing days following CPAP treatment and CPAP withdrawal nights. Compared to placebo, modafinil significantly increased awake EEG activation (faster EEG frequency) with increased alpha/delta (A/D) ratio (P < 0.0001) and fast ratio = (alpha+beta)/(delta+theta) (P < 0.0001) across the 2 days of CPAP withdrawal. The A/D ratio significantly correlated with the driving simulator response time (P = 0.015), steering variation (P = 0.002), and PVT reaction time (P = 0.006). In contrast, individual EEG band power of alpha, beta, theta, and delta did not correlate with any neurocognitive performance.
  
  
  CONCLUSIONS
  Modafinil administration during continuous positive airway pressure (CPAP) withdrawal increased awake EEG activation, which correlated to improved performance. This study provides supporting neurophysiological evidence that modafinil is a potential short-term treatment option during acute CPAP withdrawal.
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia (work performed).|Sydney Local Health District, Sydney Australia.|Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|The First Hospital of Jilin University, China.
authors.forename: Xiao Xue
authors.initials: XX
authors.lastname: Bai
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.
authors.forename: Shaun C
authors.initials: SC
authors.lastname: Williams
authors.affiliation: The First Hospital of Jilin University, China.
authors.forename: Shu Cheng
authors.initials: SC
authors.lastname: Hua
authors.affiliation: Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.|School of Physics, University of Sydney, Australia.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.|Sydney Nursing School, University of Sydney, Australia.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Marshall
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|Sydney Local Health District, Sydney Australia.|Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: D'Rozario
authors.affiliation: Sleep and Circadian Group, Woolcock Institute of Medical Research, University of Sydney, Australia.|Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia (work performed).|Sydney Local Health District, Sydney Australia.|Centre for Integrated Research and Understanding of Sleep (CIRUS), Australia.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Grunstein
mesh_terms: D001288:Attention / Q000187:drug effects / Q000502:physiology; D001334:Automobile Driving / Q000523:psychology; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D011930:Reaction Time / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D000077408:Modafinil
keywords: EEG frequency; EEG spectra; brainwave activity; motor vehicle accident; neurobehavioral performance; neurocognitive function; sleep apnea