Treatment of Narcolepsy Type 1 With Orexin: A Systematic Review

Narcolepsy is a rare, chronic neurological disorder characterized by excessive daytime sleepiness (EDS). Narcolepsy type 1 is probably caused by an autoimmune-mediated loss of orexin-producing neurons. Type 2 patients retain the physiological functioning of orexigenic neurons. The basis for treating narcolepsy type 1 with orexin-A is that if narcolepsy develops because of a loss of orexigenic neurons, then administering orexin should be able to eliminate, reduce, or prevent the impact of this loss. The aim of this review was to capture and analyze studies to elucidate the efficacy of orexin-A in the treatment of narcolepsy type 1 in humans. The search strategy included the following descriptors: "narcolepsy," "orexin," and "treatment," with filters for randomized clinical trials (RCT) and human studies. A total of 70 publications were retrieved from the databases. Duplicate records were removed before screening (n = 13), and 54 were then excluded for the following reasons: off-topic (n = 18), reviews (n = 14), use of a different intervention other than orexin (n = 14), non-human studies (n = 4), out-of-population selection criteria (n = 2), and case report (n = 2). Thus, the studies included in the review were three. Treatment of narcolepsy with orexin decreases the number of wake-REM (rapid eye movement) transitions and total time of REM sleep, although it does not increase wake time. The failure of orexin to alleviate daytime sleepiness suggests that orexin deficiency is not the only factor involved in the pathophysiology of type I narcolepsy.