Modafinil Increases Awake EEG Activation and Improves Performance in Obstructive Sleep Apnea during Continuous Positive Airway Pressure Withdrawal

Sleep. 2015 Aug 1;38(8):1297-303. doi: 10.5665/sleep.4912.


Objectives: 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.

Design: 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 CPAP was used for the first night and then withdrawn for 2 subsequent nights.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.

Settings: University teaching hospital.

Participants: Stable CPAP users (n = 23 men with OSA).

Measurement and 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.

Keywords: EEG frequency; EEG spectra; brainwave activity; motor vehicle accident; neurobehavioral performance; neurocognitive function; sleep apnea.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Attention / drug effects
  • Attention / physiology
  • Automobile Driving / psychology
  • Benzhydryl Compounds / pharmacology*
  • Benzhydryl Compounds / therapeutic use*
  • Biomarkers / analysis
  • Continuous Positive Airway Pressure*
  • Cross-Over Studies
  • Double-Blind Method
  • Electroencephalography / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Modafinil
  • Reaction Time / drug effects
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Apnea, Obstructive / physiopathology*
  • Sleep Stages / drug effects
  • Sleep Stages / physiology
  • Wakefulness / drug effects*
  • Wakefulness / physiology


  • Benzhydryl Compounds
  • Biomarkers
  • Modafinil