Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy

Objective: This is one of two separate clinical trials to evaluate the effi cacy and safety of modafinil, a novel wake-promoting agent, inpatients with excessive daytime sleepiness (EDS) associated with narcolepsy. Methods: In this 9-week, randomized, placebo-controlled, double-blind, 21-center clini cal trial, patients were randomized to receive fixed daily doses of modafin il 200 mg, modafinil 400 mg, or placebo. A placebo-controlled, 8-week treat ment discontinuation phase was included to evaluate the effects of withdraw al on patients who had been receiving modafinil. A total of 271 patients wh o were naive to modafinil received study medication:in the 9-week trial and 240 patients received;study medication in the discontinuation phase. Resul ts: Treatment with modafinil resulted in significant improvement in two obj ective measures of EDS: the Multiple Sleep Latency Test and the Maintenance of Wakefulness Test. Additionally, patient self-assessment of sleepiness w as significantly improved, as measured by the Epworth Sleepiness Scale, and level of illness was significantly reduced on the independent clinician as sessment, the Clinical Global Impression of Change. Nighttime sleep, monito red by nocturnal polysomnography, was not adversely effected with modafinil treatment compared with placebo treatment. The most frequent adverse exper ience was headache, which was not significantly greater for modafinil than placebo. During treatment discontinuation, individuals who had been receivi ng modafinil experienced a return of their EDS to baseline levels. During t reatment discontinuation, patients did not experience symptoms associated w ith amphetamine withdrawal syndrome. For up to 9 weeks of daily use there w as no evidence for the development of dependence at the dose levels studied . Conclusion: The data indicate that modafinil has an excellent safety prof ile and is very well tolerated. Modafinil is an effective treatment for exc essive daytime sleepiness in narcolepsy and shows continued efficacy with u p to 9 weeks of daily use.