This is the current release of the guideline.

Rapid eye movement sleep behavior disorder (RBD)

To provide evidence-based recommendations for the treatment of rapid eye movement sleep behavior disorder (RBD)

Adults (age 19 years and older) with rapid eye movement sleep behavior disorder (RBD)

Treatment

1. Clonazepam
2. Melatonin
3. Pramipexole
4. Paroxetine
5. L-3,4-dihydroxyphenylalanine (L-DOPA)
6. Acetylcholinesterase inhibitors
7. Zopiclone
8. Benzodiazepines
9. Yi-Gan San
10. Desipramine
11. Clozapine
12. Carbamazepine
13. Sodium oxybate

Prevention of Sleep-related Injury

1. Modify sleep environment
2. Clonazepam

A search for articles on the medical treatment of rapid eye movement sleep behavior disorder (RBD) was conducted using the PubMed database, first in February 2008, and subsequently updated in June 2009, to include the most current literature. The key words for the searches were the following: [(RBD OR Rapid Eye Movement Sleep Disorder OR REM Sleep behavior disorder) AND (treatment OR medication OR drug therapy] as well as [Rapid eye movement behavior disorder AND evaluation AND (neurological diseases OR dementia OR stroke OR sleep disorders OR Lewy body dementia OR drug induced OR multiple systems atrophy OR narcolepsy OR Parkinson's OR synucleinopathies)]. Each search was run separately and findings were merged. When the search was limited to articles published in English and regarding human adults (age 19 years and older), a total of 315 articles was identified. Abstracts from these articles were reviewed to determine if they met inclusion criteria. The literature on medical treatment of RBD was noted to comprise mostly small case series. In order to be inclusive, latitude in disorder definition was allowed and no minimum number of subjects was applied. The articles had to address at least 1 of the "PICO" questions (acronym standing for Patient, Population or Problem, provided a specific Intervention or exposure, after which a defined Comparison is performed on specified Outcomes) that were decided upon ahead of the review process (see Table 1 in the original guideline document). The literature review and pearling (i.e., checking the reference sections of search results for articles otherwise missed) provided 42 articles for review and grading.

42 articles

American Academy of Sleep Medicine (AASM) Classification of Evidence (Adapted from Oxford Centre for Evidence-based Medicine)

Evidence was graded according to the Oxford Centre for Evidence-based Medicine Levels of Evidence (see, "Rating Scheme for the Strength of the Evidence" field). All evidence grading was performed by independent review of the article by 2 members of the task force. Areas of disagreement were addressed by the task force until resolved.

The Standards of Practice Committee (SPC) of the American Academy of Sleep Medicine (AASM) commissioned among its members 7 individuals to conduct this review and develop best practice principles. Work began in December 2007 to review and grade evidence in the peer-reviewed scientific literature regarding the treatment of rapid eye movement sleep behavior disorder (RBD) in adults.

Recommendations were formulated based on the strength of clinical data and consensus attained via a modified Research and Development/University of California, Los Angeles (RAND/UCLA) Appropriateness Method. The task force developed a ranking of recommendations for increased transparency. The nomenclature for the recommendations and levels of recommendation are listed in the "Rating Scheme for the Strength of the Recommendations" field. Recommendations were downgraded if there were significant risks involved in the treatment or upgraded if expert consensus determined it was warranted.

Levels of Recommendation

A formal cost analysis was not performed and published cost analyses were not reviewed.

The paper was reviewed by content experts in the area of rapid eye movement (REM) sleep behavior disorder.

The Board of Directors of the American Academy of Sleep Medicine (AASM) approved the recommendations. They were submitted and accepted for publication in November, 2009.

The levels of evidence (1-4) and the levels of recommendations (A-C) are defined at the end of the "Major Recommendations" field.

Treatment for Rapid Eye Movement Sleep Behavior Disorder (RBD) Involves Medication and Injury Prevention

The following medications are treatment options for RBD:

1. Clonazepam is suggested for the treatment of RBD but should be used with caution in patients with dementia, gait disorders, or concomitant obstructive sleep apnea (OSA). Its use should be monitored carefully over time as RBD appears to be a precursor to neurodegenerative disorders with dementia in some patients. (Level B)
2. Melatonin is suggested for the treatment of RBD with the advantage that there are few side effects. (Level B)
3. Pramipexole may be considered to treat RBD but efficacy studies have shown contradictory results. There is little evidence to support the use of paroxetine or L-3,4-dihydroxyphenylalanine (L-DOPA) to treat RBD, and some studies have suggested that these drugs may actually induce or exacerbate RBD. There are limited data regarding the efficacy of acetylcholinesterase inhibitors, but they may be considered to treat RBD in patients with a concomitant synucleinopathy. (Level C)
4. The following medications may be considered for treatment of RBD, but evidence is very limited with only a few subjects having been studied for each medication: zopiclone, benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, carbamazepine, and sodium oxybate. (Level C)

The following are injury prevention techniques for patients with RBD:

1. Modifying the sleep environment is suggested for the treatment of patients with RBD who have sleep-related injury. (Level A)
2. Clonazepam is suggested to decrease the occurrence of sleep-related injury caused by RBD for whom pharmacologic therapy is deemed necessary. It should be used in caution in patients with dementia, gait disorders, or concomitant OSA, and its use should be monitored carefully over time. (Level B)

Definitions:

Levels of Recommendation

American Academy of Sleep Medicine (AASM) Classification of Evidence (Adapted from Oxford Centre for Evidence-based Medicine)

None provided

The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).

Appropriate treatment of rapid eye movement sleep behavior disorder to improve sleep, reduce adverse daytime effects and prevent injury

Clonazepam

• Clonazepam should be used with caution in patients with dementia, gait disorders, or concomitant obstructive sleep apnea (OSA). Its use should be monitored carefully over time as rapid eye movement sleep behavior disorder (RBD) appears to be a precursor to neurodegenerative disorders with dementia in some patients.
• In retrospective trials, the most common side effects included sedation, impotence, early morning motor incoordination, confusion, and memory dysfunction. These data suggest that clonazepam should be used with caution and oversight in patients with neurodegenerative disorders, obstructive sleep apnea, and underlying liver disease.

Melatonin

Dose-related side effects included morning headache, morning sleepiness, and delusions/hallucinations.

Pramipexole

Dopaminergic agonists may exacerbate symptoms of dementia of Lewy body (DLB), and since many patients with idiopathic RBD (IRBD) ultimately develop DLB, caution should be exercised with its use.

Paroxetine

Case reports of selective serotonin reuptake inhibitor (SSRI)-induced RBD suggest that it might exacerbate RBD. Reported side effects included nausea, dizziness, diarrhea, and thirst.

Acetylcholinesterase Inhibitors

Cholinesterase inhibitors may be associated with sleep disruption, vivid dreams and sleep-related disruptive behaviors.

Zopiclone

Side effects of cases reviewed included rash and nausea.

An implementation strategy was not provided.

Not applicable: The guideline was not adapted from another source.

American Academy of Sleep Medicine

Standards of Practice Committee

Committee Members: R. Nisha Aurora, MD; Rochelle Zak, MD; Rama K. Maganti, MD; Sanford Auerbach, MD; Kenneth R. Casey, MD; Susmita Chowdhuri, MD; Anoop Karippot, MD; Kannan Ramar, MD; David A. Kristo, MD; Timothy I. Morgenthaler, MD

All members of the American Academy of Sleep Medicine (AASM) Standards of Practice Committee and Board of Directors completed detailed conflict-of-interest statements and were found to have no conflicts of interest with regard to this subject.

This is the current release of the guideline.

Electronic copies: Available in Portable Document Format (PDF) from the American Academy of Sleep Medicine (AASM) Web site .

Print copies: Available from the Standards of Practice Committee, American Academy of Sleep Medicine, 2510 North Frontage Road, Darien, IL 60561. Web site: www.aasmnet.org .

None available

None available

This NGC summary was completed by ECRI Institute on January 11, 2011. The information was verified by the guideline developer on February 7, 2011. This summary was updated by ECRI Institute on May 20, 2011 following the U.S. Food and Drug Administration advisory on antipsychotic drugs.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions. Please contact the American Academy of Sleep Medicine (AASM) for information regarding reproduction of AASM guidelines.