Effects of modafinil on wakefulness and executive function in patients with narcolepsy experiencing late-day sleepiness

Clin Neuropharmacol. 2004 Mar-Apr;27(2):74-9. doi: 10.1097/00002826-200403000-00005.


Objectives: A modafinil daily dosing strategy promotes wakefulness in narcolepsy patients experiencing excessive daytime sleepiness; however, some patients may continue to experience late-day sleepiness. Excessive sleepiness in narcolepsy is associated with cognitive impairment. Modafinil has improved executive function in other models of excessive sleepiness. This study evaluated the effects of once-daily vs. split doses of modafinil on wakefulness and of combined doses on executive function in narcolepsy patients experiencing late-day sleepiness despite satisfactory modafinil treatment earlier in the day.

Methods: After a 2-week washout, 24 patients received 3 weeks of double-blind treatment with modafinil 400-mg once daily (7 AM) plus placebo (noon) or modafinil 600-mg split dose (400 mg, 7 AM; 200 mg, noon). Assessments included a Maintenance of Wakefulness Test (MWT) for individual regimens and the Wisconsin Card Sort Test (WCST) for treatments combined.

Results: Modafinil 600-mg split dose was significantly more effective than modafinil 400-mg once daily in improving late-day MWT scores (5 PM-7 PM; P < 0.05). Significant mean (+/- SEM) reductions from baseline of 8.2 +/- 2.7 in the total number of errors and 5.9 +/- 1.9 in total percent of errors (P < 0.05, both) were demonstrated for modafinil on the WCST. Modafinil was well tolerated; adverse events included headache (n = 1), emotional lability (n = 1), bronchitis (n = 1), and accidental injury (n = 2), with no reports of insomnia.

Conclusions: For patients with residual late-day sleepiness associated with narcolepsy, an additional 200-mg dose of modafinil taken at midday was effective in sustaining wakefulness throughout the entire waking day. Treatment with modafinil also significantly improved executive function.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / therapeutic use*
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / therapeutic use*
  • Circadian Rhythm
  • Cognition / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Male
  • Middle Aged
  • Modafinil
  • Narcolepsy / drug therapy*
  • Narcolepsy / physiopathology
  • Sleep / drug effects
  • Treatment Outcome
  • Wakefulness / drug effects*
  • Wakefulness / physiology


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Modafinil