Patients with narcolepsy who have disordered nighttime sleep benefited more from sodium oxybate (SXB) than from modafinil or placebo, according to a randomized trial that documented fewer shifts from sleep stage 2 to 4 or rapid eye movement (REM) to stage 1 or full wakefulness in patients receiving SXB.
“In this retrospective analysis, sodium oxybate appeared to improve polysomnograms and patient-reported measures of disrupted nighttime sleep in narcolepsy,” said Yves Dauvilliers, MD, PhD, from the Reference National Center for Narcolepsy at Gui de Chauliac Hospital in Montpellier, France.
“Disrupted nighttime sleep (DNS) is a clinically common complaint, occurring in almost all patients with narcolepsy,” he said. The important features of DNS are frequent shifts to lighter sleep, awakenings after sleep onset, and poor sleep quality. Researchers retrospectively analyzed data from a randomized trial to evaluate the effects of 3 common narcolepsy treatments.
“There have been no data, however, related to sleep continuity or patient sleep quality ratings,” Dr. Dauvilliers noted.
The current study, therefore, evaluated the effects of narcolepsy treatment modalities on REM and non-REM sleep-shift changes and sleep quality by retrospective analysis of data from a phase 3 randomized trial.
The findings were presented here at the American Neurological Association (ANA) 2013 Annual Meeting.
The study included 278 patients with narcolepsy who were randomly assigned to 1 of 4 treatment groups: SXB, 9 g/day; modafinil, 200 to 600 mg/day; the combination of the 2 agents; or placebo. Patients take 1 dose of SXB before going to sleep and must wake up during the night to take a second dose.
Polysomnograms and sleep quality, as assessed by the Pittsburgh Sleep Quality Index (PSQI)— specifically, question 6 (“During the past month, how would you rate your sleep quality overall?”)—were obtained at baseline and at 8 weeks. The analysis was performed on the 222 patients with evaluable sleep stage and sleep-quality PSQI data.
SXB alone and in combination with modafinil was associated with significant reductions at week 8 in the number of shifts relative to baseline. The reductions with SXB and the combination were greater than those observed with placebo. Modafinil was not associated with any shift stage reductions at week 8, Dr. Dauvilliers reported.
In shifting from stage 2/3/4 REM to stage 1/wake sleep, the median change from baseline was –13.0 (from 40.9 at baseline) in patients receiving SXB alone (P < .001) and –11.5 with the combination (P < .001). No significant reductions in these shifts were observed with modafinil alone or placebo.
In shifting from sleep-stage REM to stage 1/wake, the median change from baseline was –7.0 with SXB alone (P < .001) and –5.0 with the combination (P = .001).
“With SXB, we saw a huge decrease in the number of shift stages and from REM to stage1/wake,” he noted.
Patient-reported sleep quality also significantly improved from baseline with SXB and SXB plus modafinil. The change from baseline was –0.46 with SXB (P < .001) and –0.48 with the combination (P < .001), while modafinil and placebo demonstrated little to no change.
Nausea, vomiting, and dizziness were significantly more common with SXB than with modafinil or placebo, and more treatment discontinuations occurred among patients taking SXB alone or in combination with modafinil.
“SXB improved sleep continuity and sleep quality, and we believe this makes for an improvement in daytime functioning,” Dr. Dauvilliers concluded.
SXB Should Not Be Misused
Session moderator Beth Ann Malow, MD, professor of neurology at Vanderbilt University and director of the Vanderbilt Sleep Disorders Center, Nashville, Tennessee, emphasized that the study was conducted in patients with narcolepsy, and the findings should not be extrapolated to the general population with sleep latency.
“This is an innovative study, looking at this drug in sleep latency, since its traditional use is for improving daytime sleepiness. But it’s important to realize that this is in narcolepsy, not the general population, and this drug has abuse potential,” Dr. Malow said.
“My concern would be that the results are extrapolated to a population where the drug is not FDA [Food and Drug Administration]-approved. We must make this distinction,” she added. “I’m not saying it doesn’t have a role, but we should be careful.”