Effects of modafinil on wakefulness and executive function in patients with narcolepsy experiencing late-day sleepiness.
OBJECTIVE
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.
Schwartz
Jonathan R L
JR
Integris Southwest and Baptist Medical Centers, Oklahoma City, OK, USA. schwjr@integris-health.com
Nelson
Michael T
MT
Schwartz
Elliott R
ER
Hughes
Rod J
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002940:Circadian Rhythm; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy* / Q000503:physiopathology; D012890:Sleep / Q000187:drug effects; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil