The management of
narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1) Two tendencies characterize the conventional treatment of
narcolepsy.
Modafinil has replaced
methylphenidate and
amphetamine as the first-line treatment of
excessive daytime sleepiness (EDS) and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of
modafinil, but on no direct comparison of
modafinil versus traditional stimulants. For
cataplexy,
sleep paralysis, and
hypnagogic hallucinations, new
antidepressants tend to replace
tricyclic antidepressants and
selective serotonin reuptake inhibitors (
SSRIs) in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2) The conventional treatment of
narcolepsy is now challenged by
sodium oxybate, the
sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of
narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3) A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine
therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of
narcolepsy with
cataplexy, hypocretine-based
therapies, and
immunotherapy.