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


CONCLUSIONS
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.
Integris Sleep Disorders Center of Oklahoma, Integris Southwest and Baptist Medical Centers, 4200 S. Douglas, Suite 313, Oklahoma City, OK 73109, USA. schwjr@integris-health.com
Jonathan R L
JR
Schwartz
Neil T
NT
Feldman
June M
JM
Fry
John
J
Harsh
D000293:Adolescent; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D003913:Dextroamphetamine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D008875:Middle Aged; D000077408:Modafinil; D009290:Narcolepsy / Q000175:diagnosis / Q000188:drug therapy*; D010389:Pemoline / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D010389:Pemoline; D000077408:Modafinil; D003913:Dextroamphetamine