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Narcolepsy often presents in childhood or adolescence. Good sleep hygiene is an essential part of a total management program. Although the effects of sleep scheduling have not been well documented in the literature, some patients report that their symptoms are better controlled if they maintain a regular sleep schedule that includes 7.5 to 8 hours of sleep at night. Many clinicians also recommend deliberate brief daytime naps as part of their treatment plan. However, the majority of patients with narcolepsy require medications for symptomatic relief of daytime sleepiness..

The pharmacologic treatment of narcolepsy has depended historically on the use of psychostimulant agents, with the most common being methylphenidate, dextroamphetamine, and pemoline. In a 1991 medication survey by the American Narcolepsy Association (personal communication), 479 of 984 patients (48%) with narcolepsy were taking methylphenidate, 274 (28%) took dextroamphetamine, and 171 (17%) used pemoline. Other stimulants, which were taken by fewer than 5% of patients, included methamphetamine, d- and dl-amphetamine, mazindol, phenmetrazine, and diethylpropion.

The medications considered effective in the treatment of narcolepsy include pemoline, methylphenidate, dextroamphetamine, methamphetamine, and modafinil. Of these, modafinil has not yet been approved for use in the United States, and only methylphenidate hydrochloride and dextroamphetamine have been approved for the treatment of narcolepsy in the US.


The stimulants currently prescribed to treat narcolepsy--amphetamine, methamphetamine, methylphenidate, and pemoline--are CNS stimulants whose actions include increased wakefulness, increased vigilance, decreased sense of fatigue, and increased performance on certain tasks.

Few controlled trials have evaluated the efficacy of the stimulants in treating narcolepsy. Mitler et al. assessed the efficacy of methamphetamine in controlling EDS and improving performance in a randomized, double-blind, dose-response trial in which eight patients with narcolepsy were individually matched with normal controls. Patients received methamphetamine in doses of 0, 20 mg, or 40 to 60 mg; controls received the drug in doses of 0, 5 mg, or 10 mg.

Methylphenidate, a piperidine derivative, is the agent most frequently used to treat narcolepsy. Honda et al. reported the effects of long-term treatment with methylphenidate in 106 patients with narcolepsy. Of the included cases, 50 had been treated for 5 years or more at the time of the report. The average dosage was 30 to 60 mg daily. Marked or moderate improvement in sleep tendency.

Pemoline is pharmacologically an amphetamine-like stimulant and has effects on EDS similar to those observed with methylphenidate, although pemoline is less potent.

Mitler and colleagues compared the efficacy of low, intermediate, and high doses of methylphenidate, pemoline, and dextroamphetamine in groups of patients with narcolepsy.

Three of the stimulants used to treat narcolepsy (dextroamphetamine, methylphenidate, and methamphetamine) are considered to have a high abuse potential and are Schedule II.

Modafinil is chemically and pharmacologically distinct from currently available stimulants. Unlike amphetamines and methylphenidate, modafinil does not appear to significantly alter the release.

Modafinil has been evaluated in clinical trials with narcolepsy patients in Europe. These trials include one randomized controlled trial and several open studies, which demonstrate that modafinil.

In this 18-center trial, 285 patients with narcolepsy were randomized to one of three treatment groups: modafinil 200 mg/day, modafinil 400 mg/day, or placebo. The results of the 18-center US modafinil trial are encouraging. Patients receiving modafinil demonstrated statistically significant improvement on all objective and subjective measures of sleepiness. Modafinil-treated patients had improved ability to stay awake.