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

Sleep Med. 2003 Jan;4(1):43-9. doi: 10.1016/s1389-9457(02)00240-x.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / therapeutic use*
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / therapeutic use*
  • Dextroamphetamine / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Methylphenidate / therapeutic use
  • Middle Aged
  • Modafinil
  • Narcolepsy / diagnosis
  • Narcolepsy / drug therapy*
  • Pemoline / therapeutic use
  • Psychiatric Status Rating Scales
  • Treatment Outcome
  • Wakefulness / drug effects*


  • Benzhydryl Compounds
  • Central Nervous System Stimulants
  • Methylphenidate
  • Pemoline
  • Modafinil
  • Dextroamphetamine