Treatment modalities for narcolepsy

Abstract

Narcolepsy, a lifelong disorder, requires long-term management of symptoms. Interventions may be nonpharmacologic, such as lifestyle changes, and pharmacologic for relief of daytime sleepiness. Pharmacologic treatment of narcolepsy has depended on the use of CNS stimulants to increase wakefulness, vigilance, and performance. The medications considered effective in the treatment of narcolepsy include dextroamphetamine, pemoline, methylphenidate, methamphetamine, and modafinil; only methylphenidate hydrochloride and dextroamphetamine are approved for use in the United States. The currently available stimulants are associated with sympathomimetic side effects, limitations in efficacy, and negative effects on nighttime sleep. This has led to the development of alternative agents. Modafinil, a new wake-promoting agent, has been shown to be effective in reducing daytime sleepiness in patients with narcolepsy. The results of a United States 18-center randomized, placebo-controlled, 9-week trial of modafinil in the treatment of patients with narcolepsy has recently been reported. Patients receiving modafinil demonstrated significant improvement in all subjective and objective measures of sleepiness. Treatment with modafinil 200 mg and 400 mg daily significantly reduced mean scores on the Epworth Sleepiness Scale compared with baseline and placebo (p < 0.001) and significantly increased mean scores on the Maintenance of Wakefulness Test (p < 0.001) and the Multiple Sleep Latency Test (p < 0.01) compared with baseline and placebo. More improvement, as recorded on the Clinical Global Impression of Change scale, was seen in the modafinil group than in the placebo group at all time points (p < 0.001). Modafinil was well tolerated, with headache the only adverse event to occur significantly more often in the active treatment group (p < 0.05). These results suggest that modafinil is an important new therapeutic option for the treatment of narcolepsy.