Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder

• Published in: Sleep (New York, N.Y.) Vol. 46; no. 8
• Main Authors: During, Emmanuel H, Hernandez, Beatriz, Miglis, Mitchell G, Sum-Ping, Oliver, Hekmat, Anahid, Cahuas, Ana, Ekelmans, Adrian, Yoshino, Fuyumi, Mignot, Emmanuel, Kushida, Clete A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 14-08-2023
• Subjects: Adult; Anxiety; Anxiety Disorders; Behavior disorders; Humans; Neurological Disorders; REM Sleep Behavior Disorder - complications; REM Sleep Behavior Disorder - drug therapy; Sleep; Sodium Oxybate - therapeutic use; parasomnia; sodium oxybate; Parkinson’s disease; REM sleep behavior disorder
• DOI: 10.1093/sleep/zsad103
• EISSN: 1550-9109
• ISSN: 0161-8105

Abstract
Study Objectives
Symptomatic therapies for rapid-eye-movement (REM) sleep behavior disorder (RBD) are limited. Sodium oxybate (SXB), a gamma-aminobutyric acid (GABA)-B agonist, could be effective but has not been evaluated against placebo.
Methods
This double-blind, parallel-group, randomized, placebo-controlled trial in 24 participants was conducted at the Stanford Sleep Center. Patients were adults with definite iRBD or Parkinson’s disease and probable RBD (PD-RBD), and persistence of ≥ 2 weekly episodes despite standard therapy. Patients were randomized 1:1 to receive SXB during a 4-week titration followed by a 4-week stable dosing period. Primary outcome was number of monthly RBD episodes according to a diary filled by patients and partners. Secondary outcomes were severity, number of severe RBD episodes, and objective RBD activity on video polysomnography.
Results
Twelve iRBD and 12 PD-RBD participated (mean 65.8 years), and 22 (n = 10 SXB, 12 placebo) completed the study. Although no significant between-group difference was found, SXB showed reduction of monthly RBD episodes by 23.1 (95% CI −36.0, −10.2; p = 0.001) versus 10.5 with placebo (95% CI, −22.6, 1.6; p = 0.087). Improvement from baseline was similarly observed for RBD overall severity burden (each episode weighted for severity), number of severe episodes, and objective RBD activity per video-polysomnography. Two participants receiving SXB withdrew due to anxiety and dizziness. The majority of adverse events are otherwise resolved with dose adjustment.
Conclusion
SXB could reduce RBD symptoms; however, response was inconsistent and a large placebo effect was observed across patient-reported outcomes. Larger studies using objective endpoints are needed.
Clinical Trial
Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate
https://clinicaltrials.gov/ct2/show/NCT04006925 ClinicalTrials.gov identifier: NCT04006925
Graphical abstract
Graphical Abstract