BY SARAH OWENS
Sodium oxybate, a potent central nervous system depressor, was found effective for treating excessive daytime sleepiness (EDS) and sleep disturbances in patients with Parkinson's disease (PD), according to a small study published online on November 6 in JAMA Neurology.
Few options are available to treat sleep disturbances, including both EDS and disturbances in nighttime sleep, which are common among patients with PD, the study authors noted. They decided to test sodium oxybate because it has been found effective for treating narcolepsy type 1, and its effectiveness for PD has been tested in a small, open-label trial, which hinted at promising results.
The current findings from a randomized, blinded cohort suggest sodium oxybate "may be a powerful novel treatment option for sleep-wake disturbances in PD," the study authors, led by Fabian Büchele, MD, of the department of neurology at University Hospital Zürich in Zürich, Switzerland, wrote. However, they added, "stringent monitoring [for treatment-related complications] is necessary."
For the study, researchers from the sleep laboratory at University Hospital Zürich enrolled 18 patients with PD and EDS who had a score of at least 10 on the Epworth Sleepiness Scale (ESS), an eight-question, 24-point scale of symptoms of sleepiness, with higher scores indicating greater sleepiness. One patient withdrew consent and three patients were excluded due to a sleep apnea diagnosis, leaving 12 patients in the final study.
The researchers randomized the 12 patients in a 1:1 ratio to one of two treatment sequences: Sodium oxybate followed by placebo, or placebo followed by sodium oxybate. The participants took both medications daily as drinkable solutions at bedtime and 2.5 to four hours later for six weeks, followed by a two- to four-week washout period. Doses were titrated between 3 and 9 g per night according to efficacy and tolerability, with a maximum weekly change of 1.5 g.
The researchers' primary outcome was change of objective EDS, as determined by mean sleep latency in the Multiple Sleep Latency Test (MSLT), an objective measure of how quickly patients fall asleep in a quiet environment during the day. Secondary outcomes included change in subjective ESS scores as well as objective variables of nighttime sleep as measured on polysomnography; all outcomes were assessed at baseline and at six weeks.
At six weeks, the researchers found that, among 12 patients in the intention-to-treat population, sodium oxybate significantly improved EDS objectively (mean sleep latency, +2.9 minutes; 95% CI, 2.1 to 3.8 minutes; p=0.002) as well as subjectively (change in ESS score, −4.2 points; 95% CI, −5.3 to −3.0 points; p=0.001). Overall, eight patients (67 percent) demonstrated a positive, electrophysiologically defined treatment response. In addition, sodium oxybate significantly improved subjective sleep quality and the duration of slow-wave sleep (+72.7 minutes; 95% CI, 55.7 to 89.7 minutes; p<0.001).
However, the drug induced new obstructive sleep apnea in two patients, who were excluded from the final per-procotol analysis (n=10); in this analysis, treatment effects were even more pronounced.
The findings, the researchers concluded, "provide class I evidence for the efficacy of sodium oxybate in treating EDS and nocturnal sleep disturbance in patients with PD." However, noting the small size and short duration of the study and the observed potential adverse effects of the drug, they added, "Special monitoring with follow-up polysomnography is necessary to rule out treatment-related complications and larger follow-up trials with longer treatment durations are warranted for validation."
The main limitation to the study noted by the researchers was the small number of participants, which is sufficient to provide level 1 evidence for efficacy but not for safety, they said.
The study was funded by UCB Pharma, which provided the drug, and the Clinical Research Priority Program Sleep and Health of the University of Zurich. Dr. Büchele received speaker honoraria from Hoffmann-La Roche Pharma. He and the other authors reported no other conflicts.
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- Büchele F, Hackius M, Schreglmann SR, et al. Sodium oxybate for excessive daytime sleepiness and sleep disturbance in Parkinson disease: A randomized clinical trial. JAMA Neurol 2017; Epub 2017 Nov 6.