Efficacy and safety of modafinil for improving daytime wakefulness in patients treated previously with psychostimulants.

Objectives: To assess the efficacy and safety of modafinil for improving wakefulness in narcolepsy patients treated previously with psychostimulants.

Background: Modafinil has become a standard therapy for improving daytime wakefulness in narcolepsy patients and may be a useful therapeutic alternative to psychostimulants used to improve waking function in other medical conditions. Modafinil is chemically dissimilar to and has a pharmacological profile that differs from the psychostimulants. Modafinil has a low abuse potential and is well tolerated.

Methods: Patients (N=151) with narcolepsy who had been unsatisfactorily treated with dextroamphetamine (N=48), methylphenidate (N=66), or pemoline (N=37) were enrolled in this 6-week, open-label, multicenter study. Following a 2-week washout period, patients received modafinil once daily (Week 1, 200 mg; Weeks 2-6, 200 or 400 mg). Efficacy was evaluated at Weeks 1, 2, and 6 using the Epworth Sleepiness Scale and the Clinical Global Impression of Change. Adverse events were monitored throughout the study.

Results: Treatment with modafinil improved daytime wakefulness versus baseline regardless of which psychostimulant was taken previously. Mean ESS scores were improved after 1 week of treatment with modafinil. Improvements were maintained throughout the 6 weeks of treatment (all P<0.001 versus baseline after washout). At Week 6, 79% of all patients were considered to be clinically improved relative to post-washout baseline. The most frequent adverse events were headache, nausea, and insomnia; the majority of adverse events were mild or moderate in nature. Approximately 70% of patients were receiving 400 mg of modafinil once daily at the end of the study.

Conclusion: During this 6-week, open-label study, modafinil was an effective and well-tolerated treatment for improving daytime wakefulness in narcolepsy patients previously treated with psychostimulants.