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REM Sleep Behavior Disorder Medication

  • Author: Syed M S Ahmed, MD; Chief Editor: Selim R Benbadis, MD  more...
Updated: Sep 03, 2014

Medication Summary

The treatment of rapid eye movement sleep behavior disorder (RBD) can be challenging in some patients with underlying neurodegenerative conditions. Clonazepam has proven to be a highly successful treatment for RBD.[4, 27, 32] It is effective in nearly 90% of patients (complete benefit in 79% of patients and partial benefit in another 11% of patients), with little evidence of tolerance or abuse. The response usually begins within the first week, often on the first night.

The initial dose is 0.5 mg at bedtime. If this is ineffective, doses can be increased to 1-2 mg. With continued treatment for years, moderate limb twitching with sleep talking and more complex behaviors may reemerge. Nevertheless, control of the violent behaviors persists. The treatment should be continued indefinitely, as violent behaviors and nightmares relapse promptly with discontinuation of medications in almost all patients.

The specific mechanism of action of clonazepam in RBD is unknown but may reflect in part its serotonergic properties. In a minority of patients, particularly elderly persons, clonazepam may increase the risk of confusion or falls and may worsen obstructive sleep apnea.[27] Clonazepam is ineffective in approximately 10% of patients.

Several studies demonstrated the beneficial effect of melatonin on RBD.[29, 34] The effective dose of melatonin was 3-6 mg taken orally at bedtime. Only 36% of patients experienced adverse effects, which resolved with decreased dosing. The dosage may be increased every 5-7 days to 12 mg/day in some cases, if tolerated. The mechanism of melatonin is unclear[29] ; Kunz and Bes suggested that melatonin restores RBD-related desynchronization of the circadian rhythms.[35] Polysomnographic studies showed possible direct restoration of the mechanisms producing REM sleep muscle atonia.

Other medications, such as tricyclic antidepressants, may be effective in some patients with RBD. However, tricyclics are also known to actually precipitate RBD.[27] The newer generations of antidepressants, particularly venlafaxine and mirtazapine, are frequent precipitators or aggravators of RBD.[36]

Levodopa may be very effective in patients in whom RBD is the harbinger of Parkinson disease. In addition, anecdotal reports exist of responses to carbamazepine, clonidine, and L-tryptophan in patients with RBD.


Anxiolytics, Benzodiazepines

Class Summary

By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)


Clonazepam is very effective in the treatment of RBD in small doses. Its exact mechanism of action is unknown. There is little evidence of tolerance or abuse of the drug when it is administered in such small doses.


Decarboxylase Inhibitors

Class Summary

These agents often are indicated for patients with Parkinson disease.

Levodopa/carbidopa (Sinemet, Parcopa)


Levodopa/carbidopa may be very effective in patients in whom RBD is a harbinger of Parkinson disease. It comes in strengths of 25/100 mg, 25/250 mg, and 10/100 mg.

Contributor Information and Disclosures

Syed M S Ahmed, MD Neurologist and Sleep Specialist, Capital Neurology and Sleep Medicine; Staff Attending in Neurology and Sleep Medicine, Montgomery General Hospital; Staff Attending in Neurology and Sleep Medicine, Suburban Hospital

Syed M S Ahmed, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, Maryland State Medical Society

Disclosure: Nothing to disclose.


ABM Salah Uddin, MD Private Practice, Norwood Neurology; Consulting Staff, Department of Neurology, St Vincent's Hospital

ABM Salah Uddin, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Medical Association

Disclosure: Nothing to disclose.

Tambi Jarmi, MD Resident Physician, Department of Internal Medicine, Carraway Methodist Medical Center

Tambi Jarmi, MD is a member of the following medical societies: American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics; Eisai; Glaxo Smith Kline; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics; Lundbeck; Sepracor; Sunovion; UCB; Upsher-Smith.


Erasmo A Passaro, MD Director, Comprehensive Epilepsy Program/Clinical Neurophysiology Lab, Bayfront Medical Center Florida Center for Neurology

Erasmo A Passaro, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association, and American Society of Neuroimaging

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; UCB Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment

  1. Boeve BF, Silber MH, Saper CB, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007 Nov. 130:2770-88. [Medline].

  2. Gagnon JF, Postuma RB, Mazza S, Doyon J, Montplaisir J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol. 2006 May. 5(5):424-32. [Medline].

  3. Massicotte-Marquez J, Carrier J, Decary A, et al. Slow-wave sleep and delta power in rapid eye movement sleep behavior disorder. Ann Neurol. 2005 Feb. 57(2):277-82. [Medline].

  4. Olson EJ, Boeve BF, Silber MH. Rapid eye movement sleep behaviour disorder: demographic, clinical and laboratory findings in 93 cases. Brain. 2000 Feb. 123 ( Pt 2):331-9. [Medline].

  5. American Academy of Sleep Medicine. International Classification of Sleep Disorders: Diagnostic and Coding Manual. 2nd ed. Westchester, Ill: 2005.

  6. Hendricks JC, Morrison AR, Mann GL. Different behaviors during paradoxical sleep without atonia depend on pontine lesion site. Brain Res. 1982 May 6. 239(1):81-105. [Medline].

  7. Rye DB. Contributions of the pedunculopontine region to normal and altered REM sleep. Sleep. 1997 Sep. 20(9):757-88. [Medline].

  8. Abad VC, Guilleminault C. Review of rapid eye movement behavior sleep disorders. Curr Neurol Neurosci Rep. 2004 Mar. 4(2):157-63. [Medline].

  9. Boeve BF, Silber MH, Parisi JE, et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology. 2003 Jul 8. 61(1):40-5. [Medline].

  10. Massicotte-Marquez J, Decary A, Gagnon JF, et al. Executive dysfunction and memory impairment in idiopathic REM sleep behavior disorder. Neurology. 2008 Apr 8. 70(15):1250-7. [Medline].

  11. Boeve BF, Saper CB. REM sleep behavior disorder: a possible early marker for synucleinopathies. Neurology. 2006 Mar 28. 66(6):796-7. [Medline].

  12. Iranzo A, Molinuevo JL, Santamaria J, et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul. 5(7):572-7. [Medline].

  13. Montplaisir J. Abnormal motor behavior during sleep. Sleep Med. 2004 Jun. 5 Suppl 1:S31-4. [Medline].

  14. Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology. 1996 Feb. 46(2):388-93. [Medline].

  15. Tachibana N, Oka Y. Longitudinal change in REM sleep components in a patient with multiple system atrophy associated with REM sleep behavior disorder: paradoxical improvement of nocturnal behaviors in a progressive neurodegenerative disease. Sleep Med. 2004 Mar. 5(2):155-8. [Medline].

  16. Nihei Y, Takahashi K, Koto A, Mihara B, Morita Y, Isozumi K, et al. REM sleep behavior disorder in Japanese patients with Parkinson's disease: a multicenter study using the REM sleep behavior disorder screening questionnaire. J Neurol. 2012 Jan 10. [Medline].

  17. Sasai T, Miyamoto T, Miyamoto M, Iwanami M, Abe T, Matsuura M, et al. Impaired decision-making in idiopathic REM sleep behavior disorder. Sleep Med. 2012 Jan 26. [Medline].

  18. Postuma RB, Bertrand JA, Montplaisir J, Desjardins C, Vendette M, Rios Romenets S, et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson's disease: A prospective study. Mov Disord. 2012 Feb 9. [Medline].

  19. Eisensehr I, Linke R, Noachtar S, et al. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls. Brain. 2000 Jun. 123 ( Pt 6):1155-60. [Medline].

  20. Fantini ML, Gagnon JF, Petit D, et al. Slowing of electroencephalogram in rapid eye movement sleep behavior disorder. Ann Neurol. 2003 Jun. 53(6):774-80. [Medline].

  21. Ferini-Strambi L, Di Gioia MR, Castronovo V, Oldani A, Zucconi M, Cappa SF. Neuropsychological assessment in idiopathic REM sleep behavior disorder (RBD): does the idiopathic form of RBD really exist?. Neurology. 2004 Jan 13. 62(1):41-5. [Medline].

  22. Nightingale S, Orgill JC, Ebrahim IO, et al. The association between narcolepsy and REM behavior disorder (RBD). Sleep Med. 2005 May. 6(3):253-8. [Medline].

  23. Schenck CH, Garcia-Rill E, Segall M, et al. HLA class II genes associated with REM sleep behavior disorder. Ann Neurol. 1996 Feb. 39(2):261-3. [Medline].

  24. Peever J. Control of motoneuron function and muscle tone during REM sleep, REM sleep behavior disorder and cataplexy/narcolepsy. Arch Ital Biol. 2011 Dec 1. 149(4):[Medline].

  25. Franceschini C, Ferri R, Pizza F, Ricotta L, Vandi S, Detto S, et al. Motor events during REM sleep in patients with narcolepsy-cataplexy: a video-polysomnographic pilot study. Sleep Med. 2011 Dec. 12 Suppl 2:S59-63. [Medline].

  26. Schenck CH, Hurwitz TD, Mahowald MW. 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 Dec. 2(4):224-231. [Medline].

  27. Gagnon JF, Postuma RB, Montplaisir J. Update on the pharmacology of REM sleep behavior disorder. Neurology. 2006 Sep 12. 67(5):742-7. [Medline].

  28. Comella CL, Nardine TM, Diederich NJ, Stebbins GT. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson's disease. Neurology. 1998 Aug. 51(2):526-9. [Medline].

  29. Takeuchi N, Uchimura N, Hashizume Y, et al. Melatonin therapy for REM sleep behavior disorder. Psychiatry Clin Neurosci. 2001 Jun. 55(3):267-9. [Medline].

  30. Iranzo A, Santamaria J. Severe obstructive sleep apnea/hypopnea mimicking REM sleep behavior disorder. Sleep. 2005 Feb 1. 28(2):203-6. [Medline].

  31. Kempfner J, Sorensen GL, Sorensen HB, Jennum P. Automatic REM sleep detection associated with idiopathic rem sleep Behavior Disorder. Conf Proc IEEE Eng Med Biol Soc. 2011 Aug. 2011:6063-6. [Medline].

  32. Culebras A, Moore JT. Magnetic resonance findings in REM sleep behavior disorder. Neurology. 1989 Nov. 39(11):1519-23. [Medline].

  33. Plazzi G, Corsini R, Provini F, et al. REM sleep behavior disorders in multiple system atrophy. Neurology. 1997 Apr. 48(4):1094-7. [Medline].

  34. Boeve BF, Silber MH, Ferman TJ. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003 Jul. 4(4):281-4. [Medline].

  35. Kunz D, Bes F. Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis. Sleep. 2001 Mar 15. 24(2):183-7. [Medline].

  36. Winkelman JW, James L. Serotonergic antidepressants are associated with REM sleep without atonia. Sleep. 2004 Mar 15. 27(2):317-21. [Medline].

  37. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

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