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Treatment of REM Sleep Behavior Disorder

  • Sleep Disorders (A Iranzo, Section Editor)
  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

REM sleep behavior disorder (RBD) is a common parasomnia disorder affecting between 1 and 7 % of community-dwelling adults, most frequently older adults. RBD is characterized by nocturnal complex motor behavior and polysomnographic REM sleep without atonia. RBD is strongly associated with synucleinopathy neurodegeneration. The approach to RBD management is currently twofold: symptomatic treatment to prevent injury and prognostic counseling and longitudinal follow-up surveillance for phenoconversion toward overt neurodegenerative disorders. The focus of this review is symptomatic treatment for injury prevention. Injury occurs in up to 55 % of patients prior to treatment, even when most behaviors seem to be infrequent or minor, so patients with RBD should be treated promptly following diagnosis to prevent injury risk. A sound evidence basis for symptomatic treatment of RBD remains lacking, and randomized controlled treatment trials are needed. Traditional therapeutic mainstays with relatively robust retrospective case series level evidence include melatonin and clonazepam, which appear to be equally effective, although melatonin is more tolerable. Melatonin also has one small randomized controlled crossover trial supporting its use for RBD treatment. Melatonin dosed 3–12 mg at bedtime should be considered as the first-line therapy, followed by clonazepam 0.25–2.0 mg at bedtime if initial melatonin is judged ineffective or intolerable. However, neither agent is likely to completely stop dream enactment behaviors, so choosing a moderate target dosage of melatonin 6 mg or clonazepam 0.5 mg, or the highest tolerable dosage that reduces attack frequency and avoids adverse effects from overtreatment, is currently the most reasonable strategy. Alternative second- and third-line therapies with anecdotal efficacy include temazepam, lorazepam, zolpidem, zopiclone, pramipexole, donepezil, ramelteon, agomelatine, cannabinoids, and sodium oxybate. A novel non-pharmacological approach is a bed alarm system, although this may be most useful in patients who also report sleep walking or a history of leaving their bed during dream enactment episodes. The benefit of hypnosis, especially in those with psychiatric RBD, also requires further study. RBD is an attractive target for future neuroprotective treatment trials to prevent evolution of overt parkinsonism or memory decline, but currently, there are no known effective treatments and future trials will be necessary to determine if RBD is an actionable time point in the evolution of overt synucleinopathy.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Schenck CH et al. Chronic behavioral disorders of human REM sleep: a new category of parasomnia. Sleep. 1986;9(2):293–308.

    CAS  PubMed  Google Scholar 

  2. Schenck CH, Mahowald MW. REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP. Sleep. 2002;25(2):120–38. This landmark article describes clinical and therapeutic approaches in a large series of REM sleep behavior disorder by the sleep neurology pioneers, Schenck and Mahowald, who discovered and initially described the condition in humans at the Minnesota Regional Sleep Disorders Center based at Hennepin County Medical Center Sleep in Minneapolis.

    PubMed  Google Scholar 

  3. International classification of sleep disorders. 3rd ed. Westchester, IL: American Academy of Sleep Medicine 2014.

  4. Boeve BF. REM sleep behavior disorder: updated review of the core features, the REM sleep behavior disorder-neurodegenerative disease association, evolving concepts, controversies, and future directions. Ann N Y Acad Sci. 2010;1184:15–54. This encyclopedic review article comprehensively reviews clinical, pathophysiologic, pathologic, imaging, and treatment aspects of REM sleep behavior disorder, including alternative approaches to treatment in refractory cases such as the use of sodium oxybate.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chiu HF et al. Sleep-related injury in the elderly—an epidemiological study in Hong Kong. Sleep. 2000;23(4):513–7.

    CAS  PubMed  Google Scholar 

  6. Ohayon MM, Schenck CH. Violent behavior during sleep: prevalence, comorbidity and consequences. Sleep Med. 2010;11(9):941–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Boeve BF et al. Validation of the Mayo Sleep Questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med. 2011;12(5):445–53.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Boot BP et al. Probable rapid eye movement sleep behavior disorder increases risk for mild cognitive impairment and Parkinson disease: a population-based study. Ann Neurol. 2012;71(1):49–56.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Boeve BF et al. Clinicopathologic correlations in 172 cases of rapid eye movement sleep behavior disorder with or without a coexisting neurologic disorder. Sleep Med. 2013;14(8):754–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Iranzo A et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet Neurol. 2013;12(5):443–53.

    Article  PubMed  Google Scholar 

  11. Schenck CH et al. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 2013;14(8):744–8.

    Article  PubMed  Google Scholar 

  12. Iranzo A et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLoS One. 2014;9(2):e89741.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Postuma RB et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology. 2009;72(15):1296–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Iranzo A et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected]. Lancet Neurol. 2010;9(11):1070–7.

    Article  CAS  PubMed  Google Scholar 

  15. Schenck CH et al. Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy—a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group. Sleep Med. 2013;14(8):795–806. This consensus position paper of the International RBD Study Group proposes future approaches to symptomatic and neuroprotective clinical trials for REM sleep behavior disorder.

    Article  CAS  PubMed  Google Scholar 

  16. Hancock KL et al. Quantitative analyses of REM sleep without atonia in children and adolescents with REM sleep behavior disorder. Minn Med. 2014;97(5):43.

    PubMed  Google Scholar 

  17. Lloyd R et al. Characteristics of REM sleep behavior disorder in childhood. J Clin Sleep Med. 2012;8(2):127–31.

    PubMed  PubMed Central  Google Scholar 

  18. Dauvilliers Y et al. Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy. Sleep Med. 2013;14(8):775–81.

    Article  PubMed  Google Scholar 

  19. St Louis EK et al. Lesional REM sleep behavior disorder localizes to the dorsomedial pons. Neurology. 2014;83(20):1871–3.

    Article  PubMed  PubMed Central  Google Scholar 

  20. McCarter SJ et al. Neuroimaging-evident lesional pathology associated with REM sleep behavior disorder. Sleep Med. 2015;16(12):1502–10.

    Article  PubMed  Google Scholar 

  21. Iranzo A et al. Rapid eye movement sleep behavior disorder and potassium channel antibody-associated limbic encephalitis. Ann Neurol. 2006;59(1):178–81.

    Article  PubMed  Google Scholar 

  22. Cornelius JR et al. Sleep manifestations of voltage-gated potassium channel complex autoimmunity. Arch Neurol. 2011;68(6):733–8.

    Article  PubMed  Google Scholar 

  23. Lee K, et al. The Prevalence and Characteristics of REM Sleep without Atonia (RSWA) in Patients Taking Antidepressants. J Clin Sleep Med. 2015.

  24. Postuma RB et al. Antidepressants and REM sleep behavior disorder: isolated side effect or neurodegenerative signal? Sleep. 2013;36(11):1579–85.

    PubMed  PubMed Central  Google Scholar 

  25. McCarter SJ et al. Antidepressants Increase REM Sleep Muscle Tone in Patients with and without REM Sleep Behavior Disorder. Sleep. 2015;38(6):907–17.

    PubMed  PubMed Central  Google Scholar 

  26. Feinstein M SR, Sandness DJ, Timm PC, Lipford M, Tippmann-Peikert M, Junna M, Silber MH, Boeve BF, St. Louis EK. Counseling of the patient with idiopathic REM sleep behavior disorder and incidental polysomnographic REM sleep without atonia: a retrospective analysis. Sleep. 2016;39(Suppl (abstract)):A239.

  27. Arnaldi D AE, St. Louis EK, Postuma RB, Arnulf I. Idiopathic REM sleep behavior disorder and neurodegenerative risk: to tell or not to tell the patient, and how to minimize the risk? (Unpublished observations, manuscript).

  28. Boeve BF et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology. 1998;51(2):363–70.

    Article  CAS  PubMed  Google Scholar 

  29. Comella CL et al. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson’s disease. Neurology. 1998;51(2):526–9.

    Article  CAS  PubMed  Google Scholar 

  30. Olson EJ et al. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000;123(Pt 2):331–9.

    Article  PubMed  Google Scholar 

  31. McCarter SJ et al. Factors associated with injury in REM sleep behavior disorder. Sleep Med. 2014;15(11):1332–8. This paper reviewed the frequency of injury in untreated REM sleep behavior disorder, finding that 55% of idiopathic RBD patients reported injury prior to treatment, 11.3% with serious injuries such as subdural hematomas. While not discussing treatment per se, the alarming frequency of injury suggest that treatment to prevent injury should be a major priority in the care of RBD patients.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Chokroverty S. Editorial: “Injurious RBD and DEB frequency: are they related?”. Sleep Med. 2014;15(11):1287.

    Article  PubMed  Google Scholar 

  33. Schenck CH et al. Symposium: Normal and abnormal REM sleep regulation: REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature. J Sleep Res. 1993;2(4):224–31.

    Article  PubMed  Google Scholar 

  34. McCarter SJ et al. REM sleep behavior disorder and REM sleep without atonia as an early manifestation of degenerative neurological disease. Curr Neurol Neurosci Rep. 2012;12(2):182–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Boeve BF et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130(Pt 11):2770–88.

    Article  CAS  PubMed  Google Scholar 

  36. Anderson KN, Shneerson JM. Drug treatment of REM sleep behavior disorder: the use of drug therapies other than clonazepam. J Clin Sleep Med. 2009;5(3):235–9. This article assessed alternative treatments to clonazepam used in open clinical experience in REM sleep behavior disorder management, especially finding zopiclone as a suitable alternative in some patients.

    PubMed  PubMed Central  Google Scholar 

  37. Brooks PL, Peever JH. Impaired GABA and glycine transmission triggers cardinal features of rapid eye movement sleep behavior disorder in mice. J Neurosci. 2011;31(19):7111–21.

    Article  CAS  PubMed  Google Scholar 

  38. Lapierre O, Montplaisir J. Polysomnographic features of REM sleep behavior disorder: development of a scoring method. Neurology. 1992;42(7):1371–4.

    Article  CAS  PubMed  Google Scholar 

  39. Ferri R et al. An observational clinical and video-polysomnographic study of the effects of clonazepam in REM sleep behavior disorder. Sleep Med. 2013;14(1):24–9.

    Article  PubMed  Google Scholar 

  40. Li SX et al. A prospective, naturalistic follow-up study of treatment outcomes with clonazepam in rapid eye movement sleep behavior disorder. Sleep Med. 2016;21:114–20. This excellent new open study of clonazepam in 39 RBD patients found that an effective Treatment response, as defined by a complete elimination of sleep-related injuries and potentially injurious behaviors to self and/or to bed partner, was reported in 66.7% of the patients. Interestingly, there was no apparent effect on polysomnographic REM atonia, and decreased nightmarish dream content seemed most associated with efficacy.Patients with earlier onset RBD symptoms or history of co-morbid sleep apnea showed less beneficial treatment responses to clonazepam.

    Article  PubMed  Google Scholar 

  41. Bonakis A et al. REM sleep behaviour disorder (RBD) and its associations in young patients. Sleep Med. 2009;10(6):641–5.

    Article  PubMed  Google Scholar 

  42. Schenck CH, Mahowald MW. Long-term, nightly benzodiazepine treatment of injurious parasomnias and other disorders of disrupted nocturnal sleep in 170 adults. Am J Med. 1996;100(3):333–7. This large case series reported the efficacy and long term tolerability of clonazepam for treatment of injurious parasomnias including 52 patients with REM sleep behavior disorder, finding effective control in the majority of patients.

    Article  CAS  PubMed  Google Scholar 

  43. McCarter SJ et al. Treatment outcomes in REM sleep behavior disorder. Sleep Med. 2013;14(3):237–42. This case series of 45 REM sleep behavior disorder patients remains the largest comparative study between melatonin and clonazepam to date, finding through survey based patient reported outcomes that both treatments were approximately equally effective at reducing RBD frequency and severity, while melatonin was better tolerated.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Aurora RN et al. Best practice guide for the treatment of REM sleep behavior disorder (RBD). J Clin Sleep Med. 2010;6(1):85–95. This article comprehensively assessed available literature through 2010 concerning REM sleep behavior disorder treatment, and as the present review, concentrated on clonazepam and melatonin but also examining then published alternative., and also provided evidence level ratings for various treatments, reporting Level A evidence for safety measures, Level B for clonazepam and melatonin, and Level C for other alternatives such as pramipexole, zopiclone, benzodiazepines other than clonazepam, Yi-Gan San, desipramine, clozapine, carbamazepine, and sodium oxybate.

    PubMed  PubMed Central  Google Scholar 

  45. Kunz D, Mahlberg R. A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder. J Sleep Res. 2010;19(4):591–6. This small randomized crossover trial showed efficacy of melatonin and its apparent biological impact on improving REM sleep atonia in 8 patients with REM sleep behavior disorder.

    Article  PubMed  Google Scholar 

  46. Kunz D, Bes F. Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation. Mov Disord. 1999;14(3):507–11.

    Article  CAS  PubMed  Google Scholar 

  47. Takeuchi N et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001;55(3):267–9.

    Article  CAS  PubMed  Google Scholar 

  48. Boeve BF et al. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281–4. This case series showed practical clinical utility for melatonin therapy for REM sleep behavior disorder.

    Article  PubMed  Google Scholar 

  49. Attenburrow ME et al. Low dose melatonin improves sleep in healthy middle-aged subjects. Psychopharmacology (Berl). 1996;126(2):179–81.

    Article  CAS  Google Scholar 

  50. Zhdanova IV et al. Effects of low oral doses of melatonin, given 2–4 hours before habitual bedtime, on sleep in normal young humans. Sleep. 1996;19(5):423–31.

    CAS  PubMed  Google Scholar 

  51. Kunz D et al. Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. J Clin Endocrinol Metab. 2004;89(1):128–34.

    Article  CAS  PubMed  Google Scholar 

  52. Nomura T et al. Use of ramelteon for the treatment of secondary REM sleep behavior disorder. Intern Med. 2013;52(18):2123–6.

    Article  PubMed  Google Scholar 

  53. Esaki Y, et al. An Open-Labeled Trial of Ramelteon in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. J Clin Sleep Med. 2016.

  54. St. Louis EK, McCarter SJ, Boeve BF. Ramelteon for idiopathic REM sleep behavior disorder: implications for pathophysiology and future treatment trials. JCSM. 2016;12(5):643–5.

  55. Bonakis A et al. Agomelatine may improve REM sleep behavior disorder symptoms. J Clin Psychopharmacol. 2012;32(5):732–4.

    Article  PubMed  Google Scholar 

  56. Zucconi M, et al. Agomelatine in idiopathic REM sleep behavior disorder. 37. 2014;Supplement:A212.

  57. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;2:CD001520.

    Google Scholar 

  58. Takeda Pharmaceuticals. Rozerem prescribing information. Accessed July 27, 2016. Available from: http://general.takedapharm.com/content/file.aspx?applicationcode=2bcc07ca-d9c0-4704-9a28-963127115641&filetypecode=rozerempi&cacheRandomizer=cf7c4908-1b22-4b10-a7b0-df26e88fb0a1.

  59. Verhave PS et al. REM sleep behavior disorder in the marmoset MPTP model of early Parkinson disease. Sleep. 2011;34(8):1119–25.

    PubMed  PubMed Central  Google Scholar 

  60. Fantini ML et al. The effects of pramipexole in REM sleep behavior disorder. Neurology. 2003;61(10):1418–20.

    Article  CAS  PubMed  Google Scholar 

  61. Schmidt MH et al. Use of pramipexole in REM sleep behavior disorder: results from a case series. Sleep Med. 2006;7(5):418–23.

    Article  PubMed  Google Scholar 

  62. Sasai T et al. Factors associated with the effect of pramipexole on symptoms of idiopathic REM sleep behavior disorder. Parkinsonism Relat Disord. 2013;19(2):153–7.

    Article  PubMed  Google Scholar 

  63. Kumru H et al. Lack of effects of pramipexole on REM sleep behavior disorder in Parkinson disease. Sleep. 2008;31(10):1418–21.

    PubMed  PubMed Central  Google Scholar 

  64. Shiromani PJ et al. Acetylcholine and the regulation of REM sleep: basic mechanisms and clinical implications for affective illness and narcolepsy. Annu Rev Pharmacol Toxicol. 1987;27:137–56.

    Article  CAS  PubMed  Google Scholar 

  65. Jones BE. The organization of central cholinergic systems and their functional importance in sleep-waking states. Prog Brain Res. 1993;98:61–71.

    Article  CAS  PubMed  Google Scholar 

  66. Holsboer-Trachsler E et al. Effects of the novel acetylcholinesterase inhibitor SDZ ENA 713 on sleep in man. Neuropsychopharmacology. 1993;8(1):87–92.

    Article  CAS  PubMed  Google Scholar 

  67. Ringman JM, Simmons JH. Treatment of REM sleep behavior disorder with donepezil: a report of three cases. Neurology. 2000;55(6):870–1.

    Article  CAS  PubMed  Google Scholar 

  68. Di Giacopo R et al. Rivastigmine as alternative treatment for refractory REM behavior disorder in Parkinson’s disease. Mov Disord. 2012;27(4):559–61.

    Article  PubMed  Google Scholar 

  69. Brunetti V et al. Rivastigmine for refractory REM behavior disorder in mild cognitive impairment. Curr Alzheimer Res. 2014;11(3):267–73.

    Article  CAS  PubMed  Google Scholar 

  70. Carlander B, Touchon J, Ondze B, Billard M. REM sleep behavior disorder induced by cholinergic treatment in Alzheimer’s disease. J Sleep Res. 1996;5 suppl 1:28.

    Google Scholar 

  71. Shinno H et al. Successful treatment with Yi-Gan San for rapid eye movement sleep behavior disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(7):1749–51.

    Article  PubMed  Google Scholar 

  72. Shneerson JM. Successful treatment of REM sleep behavior disorder with sodium oxybate. Clin Neuropharmacol. 2009;32(3):158–9.

    Article  CAS  PubMed  Google Scholar 

  73. Howell MJ et al. A novel therapy for REM sleep behavior disorder (RBD). J Clin Sleep Med. 2011;7(6):639–44A. This report in four medication refractory REM sleep behavior disorder patients showed evidence for decreased injury and symptoms, offering a novel approach to therapy without adverse effects.

    PubMed  PubMed Central  Google Scholar 

  74. Dumitrascu O et al. Parasomnia overlap disorder: a distinct pathophysiologic entity or a variant of rapid eye movement sleep behavior disorder? A case series. Sleep Med. 2013;14(11):1217–20.

    Article  PubMed  Google Scholar 

  75. Howell MJ, Schenck CH. Rapid eye movement sleep behavior disorder and neurodegenerative disease. JAMA Neurol. 2015;72(6):707–12.

    Article  PubMed  Google Scholar 

  76. Hurwitz TD et al. A retrospective outcome study and review of hypnosis as treatment of adults with sleepwalking and sleep terror. J Nerv Ment Dis. 1991;179(4):228–33.

    Article  CAS  PubMed  Google Scholar 

  77. Hauri PJ et al. The treatment of parasomnias with hypnosis: a 5-year follow-up study. J Clin Sleep Med. 2007;3(4):369–73.

    PubMed  PubMed Central  Google Scholar 

  78. Larsen V SD, Richardson J, Boeve BF, Silber MH, St. Louis EK. Clinical characteristics and treatment outcomes of patients treated with hypnosis for parasomnias. Sleep. 2016;39(Suppl (abstract)):A237.

  79. Chagas MH et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014;39(5):564–6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number 1 UL1 RR024150-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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  1. Center for Sleep Medicine and Departments of Neurology and Medicine, Mayo Clinic, Rochester, MN, 55905, USA

    Youngsin Jung MD, PhD & Erik K. St. Louis MD

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Erik K. St Louis reports personal fees from Inspire, Inc., and Wiley-Blackwell, outside the submitted work.

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Jung, Y., St. Louis, E.K. Treatment of REM Sleep Behavior Disorder. Curr Treat Options Neurol 18, 50 (2016). https://doi.org/10.1007/s11940-016-0433-2

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