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

AbstractOBJECTIVES:
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.
AuthorsJonathan R L Schwartz, Michael T Nelson, Elliott R Schwartz, Rod J Hughes
JournalClinical neuropharmacology (Clin Neuropharmacol) 2004 Mar-Apr Vol. 27 Issue 2 Pg. 74-9 ISSN: 0362-5664 [Print] United States
PMID15252267 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
Chemical References
  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Modafinil
Topics
  • Adolescent
  • Adult
  • Aged
  • Benzhydryl Compounds (administration & dosage, therapeutic use)
  • Central Nervous System Stimulants (administration & dosage, 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, physiopathology)
  • Sleep (drug effects)
  • Treatment Outcome
  • Wakefulness (drug effects, physiology)

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