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Observation
January 2016

A Case of Rapid Eye Movement Sleep Behavior Disorder in Parkinson Disease Treated With Sodium Oxybate

Author Affiliations
  • 1Stanford Sleep Medicine Center, Redwood City, California
  • 2UBC Health Sciences Center Hospital, Vancouver, British Columbia, Canada
JAMA Neurol. 2016;73(1):126-127. doi:10.1001/jamaneurol.2015.2904

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by altered dream mentation, vocalizations, and dream enactment behavior (DEB). The motor behavior is often aggressive, resulting in potential injury to the patient or bed partner. Clonazepam and melatonin are considered standard treatments. Limited data exist on the use of alternative agents when standard medications fail. We report a case of successfully treated RBD in advanced Parkinson disease (PD) with sodium oxybate in a patient refractory to both standard and alternative pharmacologic agents.

Report of a Case

A man in his late 60s with a 15-year history of PD (Hoehn and Yahr score, 3) and 20-year history of RBD presented with worsening DEB. While the patient’s daytime motor symptoms improved following deep brain stimulation, episodes of DEB became progressively more violent, resulting in assault on his wife and self-injurious behaviors. Yelling occurred multiple times per night. Violent behaviors were reported every other night, such as punching through walls or striking furniture (Figure). Initial polysomnography demonstrated obstructive sleep apnea (OSA), with an Apnea Hypopnea Index score of 8.5. Given the mild severity of OSA, risk of interaction with continuous positive airway pressure device during DEB, and patient preference, conservative treatment was initiated.

Figure.
Rapid Eye Movement Behavior Disorder and Violent Events
Rapid Eye Movement Behavior Disorder and Violent Events

Despite removing all objects from the bedroom and laying the mattress onto the floor, the patient continued to strike out at walls and the ground, causing self-injury and damage to property during dream enactment behavior.

Violent behaviors persisted despite treatment with standard agents (clonazepam and melatonin). The patient’s maximum tolerated dose of clonazepam was 1 mg, as higher doses resulted in drowsiness. The addition of melatonin, titrated to 12 mg, also failed to control symptoms. Prazosin, ramelteon, cyproheptadine, and eszopiclone were subsequently added. Despite this extensive regimen, the violent behaviors increased in frequency. One severe episode resulted in a head laceration after striking the wall, requiring emergency department evaluation with unremarkable neuroimaging. Given the persistent threat of violent, potentially fatal behaviors, a trial of sodium oxybate was initiated under supervision during polysomnography. Dosing was titrated to 2.5 g twice nightly, which was based on a case report1 and guidelines for treatment of RBD.2 Treatment with sodium oxybate resulted in complete cessation of DEB episodes for 2 months, representing a reduction from the patient’s previous frequency of nearly every other night. He subsequently had 3 breakthrough episodes during the first half of the night and his first dose was increased to 3 g, with no further violent episodes reported to date. Importantly, the patient tolerated sodium oxybate well, without developing adverse medication events or significant worsening of his OSA. Repeat polysomnography on sodium oxybate demonstrated an Apnea Hypopnea Index score of 12.8, but again, the patient preferred to avoid a trial of continuous positive airway pressure given his improvement in DEB.

The Stanford University institutional review board determined that this project did not meet the federal definition of research with human participants, and institutional review board approval was not required.

Discussion

Rapid eye movement sleep behavior disorder is characterized by DEB, which can result in injury. Limited data exist on the use of alternative agents when standard medications fail in both idiopathic RBD and RBD with PD. Prazosin, an α1-adrenergic antagonist, has documented efficacy in patients with posttraumatic nightmares and disruptive nocturnal behaviors.3,4 In one case report of refractory idiopathic RBD, sodium oxybate effectively controlled dream-enactment behavior, with sustained improvement during 12 months of follow-up. Additionally, sodium oxybate was shown to improve daytime sleepiness in PD in an open-label study.5 Our patient experienced improvement in DEB with sodium oxybate. He tolerated the medication well, without development of serious adverse events.

Conclusions

To our knowledge, this is the first reported case of a patient with advanced PD and severe refractory RBD treated safely and successfully with sodium oxybate. While the exact mechanism by which sodium oxybate suppresses RBD is unclear, this medication may be of benefit to a patient with refractory RBD at risk for serious injuries. The findings from this observation and previous studies suggest the importance of future research to examine the potential therapeutic role of sodium oxybate in PD and RBD.

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Article Information

Corresponding Author: Chad Ruoff, MD, Stanford Sleep Medicine Center, 450 Broadway, Redwood City, CA 94063 (cruoff@stanford.edu).

Published Online: November 23, 2015. doi:10.1001/jamaneurol.2015.2904.

Conflict of Interest Disclosures: Dr Ruoff has served on advisory boards and as an unpaid consultant for Jazz Pharmaceuticals. No other disclosures were reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
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Aurora  RN, Zak  SZ, Maganti  RK,  et al.  Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6(1):85-95. PubMed
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Raskind  MA, Peskind  ER, Hoff  DJ,  et al.  A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007;61(8):928-934.PubMedArticle
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Mysliwiec  V, O’Reilly  B, Polchinski  J, Kwon  HP, Germain  A, Roth  BJ.  Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors. J Clin Sleep Med. 2014;10(10):1143-1148. PubMed
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Ondo  WG, Perkins  T, Swick  T,  et al.  Sodium oxybate for excessive daytime sleepiness in Parkinson disease: an open-label polysomnographic study. Arch Neurol. 2008;65(10):1337-1340. PubMed
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