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.
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.
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.
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.
From Integris Southwest and Baptist Medical Centers, Oklahoma City, OK.
Supported by a grant from Cephalon, Inc., West Chester, Pennsylvania.
Reprints: Jonathan R.L. Schwartz, MD, Integris Sleep Disorders Center of Oklahoma, Integris Southwest and Baptist Medical Centers, 4200 South Douglas, Suite 313, Oklahoma City, OK 73109 (e-mail: email@example.com).