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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, 28, 33]}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.^[28]Clonazepam is ineffective in approximately 10% of patients.

Several studies demonstrated the beneficial effect of melatonin on RBD.^{[30, 35]}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^[30]; Kunz and Bes suggested that melatonin restores RBD-related desynchronization of the circadian rhythms.^[36]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.^[28]The newer generations of antidepressants, particularly venlafaxine and mirtazapine, are frequent precipitators or aggravators of RBD.^[37]

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.

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)

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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.

Class Summary

These agents often are indicated for patients with Parkinson disease.

Levodopa/carbidopa (Sinemet, Parcopa)

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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.

Questions

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Author

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.

Coauthor(s)

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 Morsani College of Medicine

Selim R Benbadis, 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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Bioserenity (DigiTrace), Brain Sentinel, Cavion, Ceribell, Eisai, Greenwich, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Serve(d) as a speaker or a member of a speakers bureau for: Bioserenity (DigiTrace), Brain Sentinel, Cavion, Ceribell, Eisai, Greenwich, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion<br/>Received research grant from: LivaNova, Greenwich, SK biopharmaceuticals, Takeda,.

Acknowledgements

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

REM Sleep Behavior Disorder Medication

Medication Summary

Anxiolytics, Benzodiazepines

Class Summary

Clonazepam (Klonopin)

Clonazepam (Klonopin)

Decarboxylase Inhibitors

Class Summary

Levodopa/carbidopa (Sinemet, Parcopa)

Levodopa/carbidopa (Sinemet, Parcopa)

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REM Sleep Behavior Disorder Medication

Medication Summary

Anxiolytics, Benzodiazepines

Class Summary

Clonazepam (Klonopin)

Clonazepam (Klonopin)

Decarboxylase Inhibitors

Class Summary

Levodopa/carbidopa (Sinemet, Parcopa)

Levodopa/carbidopa (Sinemet, Parcopa)

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