Effect of sodium oxybate on disrupted nighttime sleep in patients with narcolepsy

Abstract

SUMMARYThis post hoc analysis evaluated the dose-related effects of sodium oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of sodium oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or sodium oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses. Relative to baseline, significant dose-dependent reductions in the number of shifts per hour from Stages N2/3/rapid eye movement and Stages N2/3 to Stage N1/ Wake were observed at week 8 with sodium oxybate (P < 0.05); sodium oxybate 6-and 9-g doses also resulted in similar reductions in shifts per hour of rapid eye movement to Stage N1/Wake (both P < 0.05). Across all shift categories, the shift reductions with sodium oxybate 9 g were significantly greater than those observed with placebo (P < 0.05). Improvements from baseline in reported sleep quality were significantly greater with sodium oxybate 4.5 and 9 g at week 8 (P < 0.05). Correlations between change from baseline in number of shifts per hour to Stage N1/Wake and cataplexy frequency, patient-reported nocturnal sleep quality, and excessive daytime sleepiness assessed using the Epworth Sleepiness Scale were numerically highest for the sodium oxybate 9-g dose across all sleep stage shift categories. In these patients with narcolepsy, sodium oxybate showed improvements in the sleep continuity and nocturnal sleep quality that are characteristic of disrupted nighttime sleep (ClinicalTrials.gov identifier NCT00049803).

Therapy for Cataplexy

“…A cessation of the therapy is not associated with a rebound of cataplexy. The delay of maximal response to treatment can vary between 94 and 279 days [55]. In a meta-analysis evaluating the efficacy of GHB in all clinical symptoms of narcolepsy, the reduction of cataplexies was confirmed.…”

“…Sodium oxybate is the sodium salt of gamma hydroxybutyrate (GHB). It acts as an agonist to the gamma-aminobutyric acid receptor B [55]. Because of a short half-time (G 60 min) sodium oxybate needs to be taken twice a night.…”

“…The cessation of LC activity is suspected to result in rebound activation with increased responsiveness during daytime with a positive effect on EDS and cataplexy [56]. A dose dependent effect on cataplexy was proven in several randomized trials [55] with a moderate decrease of anticataplectic effect by time. Side effects are nausea, dizziness, vomiting, somnolence, enuresis, and tremor.…”

Sleep in neurological disorders, sleep apnea, sleep duration and body weight

“…Roth et al . (), in a post‐hoc analysis of a pharmacological trial with sodium oxybate, describe the effects of this substance on night‐time sleep in patients with narcolepsy. Different doses of sodium oxybate (4.5, 6, 9 g) were compared to placebo and evaluated in a sample of 159 patients with narcolepsy.…”

“…Four papers in this issue of JSR focus on sleep-related issues and neurological disorders, such as narcolepsy, bruxism, REM sleep behaviour disorder and multiple sclerosis. Roth et al (2017), in a post-hoc analysis of a pharmacological trial with sodium oxybate, describe the effects of this substance on night-time sleep in patients with narcolepsy. Different doses of sodium oxybate (4.5, 6, 9 g) were compared to placebo and evaluated in a sample of 159 patients with narcolepsy.…”