Treatment of REM Sleep Behavior Disorder

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.