The effect of intranasal orexin-A (hypocretin-1) on sleep, wakefulness and attention in narcolepsy with cataplexy

Narcolepsy with cataplexy is a sleep dysregulation disorder with alterations of REM sleep, i.e., sleep onset REM periods and REM sleep instability. Deficient orexin-A (hypocretin-1) signaling is assumed to be a major cause of narcolepsy with cataplexy. In this study we investigated fourteen subjects with narcolepsy with cataplexy in a within-subject, random-order crossover, placebo-controlled design. Patients received double-blinded intranasal orexin-A (435 nmol) or sterile water (placebo) in the morning. Administration was preceded by an adaptation night and followed by a modified maintenance of wakefulness test, attention testing and a second full night of polysomnographic recording. We found comparable sleep behavior during the adaptation nights between both conditions. After orexin-A administration patients had less wake-REM sleep transitions and a decreased REM sleep duration. In the subsequent night, patients showed an increased N2 duration. In the test of divided attention, patients had fewer false reactions after orexin-A administration. Our results support orexin-A to be a REM sleep stabilizing factor and provide functional signs for effects of orexin-A on sleep alterations and attention in narcolepsy with cataplexy.