Sodium oxybate, a drug used to treat narcolepsy, may improve excessive daytime sleep and sleep disturbances in patients with Parkinson disease (PD), according to preliminary evidence from a small study in Switzerland. The findings were published online on November 6, 2017 in JAMA Neurology.1
Patients with PD commonly experience sleep disturbances, for which few treatment options exist. A previous open-label trial suggested that sodium oxybate may improve daytime sleepiness in PD. While promising, the results were limited by lack of control group and the use of subjective sleep assessments rather than objective measures.2
To provide more concrete evidence, researchers conducted a double-blind placebo-controlled crossover phase 2a study at the University Hospital Zurich between January 2015 and February 2017. It included 12 patients (2 women, 10 men) with PD and excessive daytime sleepiness who were randomized to sodium oxybate drinkable solution or placebo for 6 weeks, followed by a washout period, after which participants switched treatment groups.
Sodium oxybate was taken according to the standard narcolepsy protocol, as a drinkable solution at bedtime with a second dose 2.5 to 4 hours later, and individually titrated to a dose of 3.0 to 9.0 grams per night. One patient dropped out due to an unrelated adverse event; 11 patients completed the study. Patients were evaluated with polysomnography in the sleep laboratory at baseline and at 6 weeks.
Key Results for the Intention to Treat Population (12 Patients)
• Mean sleep latency increased by 2.9 minutes with sodium oxybate versus placebo (P = .002)
• Slow-wave sleep duration increased by 72.7 minutes vs placebo (P < .001)
• Subjective sleep quality on the Epworth Sleepiness Scale (ESS) significantly improved (P = .001)
• Sodium oxybate was generally well tolerated but: 2 patients developed new obstructive sleep apnea; and 1 patient developed non-REM parasomnia
• there were no signs of abuse or dependency
The authors pointed out that 8 patients in the sodium oxybate group experienced clinically significant improvement of over 50% in mean sleep latency. Also, the ESS (Epworth Sleepiness Scale) score for subjective sleep quality normalized in 50% of patients on sodium oxybate. However, it was noted that the study was limited by small numbers and does not provide reliable information on safety outcomes, for which future studies are needed.
“Sodium oxybate may be a powerful novel treatment option for sleep-wake disturbances in PD. However, stringent monitoring is necessary . . . and larger follow-up trials with longer treatment durations are warranted for validation,” concluded first author Fabian Büchele, MD, of the University Hospital Zurich, Switzerland.
Take Home Points
• Results of the first double-blind placebo controlled study of the narcolepsy drug sodium oxybate show significantly improved sleepiness and nighttime sleep in patients with PD
• The study was too small to produce reliable safety results
• Larger, longer term studies are needed to confirm the results and provide more safety information
1. 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. 2018;75:114-118.
2. OndoWG, Perkins T, Swick T, et al. Sodium oxybate for excessive daytime sleepiness in Parkinson disease: an open-label polysomnographic study. Arch Neurol. 2008;65:1337-1340.