Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.

Current Treatment Options for REM Sleep Behaviour Disorder

“…The results of this review are, in general, in agreement with those of other previous reviews [88][89][90][91][92][93][94][95][96][97][98]. Ideally, the design of therapeutical trials for RBD should pursue two main types of objectives: the adequate symptomatic therapy for RBD symptoms and the possibility of developing neuroprotective (preventive) strategies.…”

Isolated REM sleep behaviour disorder: current diagnostic procedures and emerging new technologies

“…The initial suspicion of iRBD is usually raised by a bed partner, who has noticed unusual behaviours during sleep. These often include yelling, kicking, punching and more complex actions, such as moving items around the room [ 16 ]. This may prompt an appointment with the individual’s GP for investigation, but can also be left unattended for many years, especially if iRBD symptoms fluctuate, are considered medically unimportant, or if there is no bed partner at all [ 17 ].…”

Current Insights into the Risks of Using Melatonin as a Treatment for Sleep Disorders in Older Adults

“… 20–24 Some studies have claimed efficacy of melatonin in reducing the symptoms of REM sleep behavior disorder, however recent randomized control trials have not shown benefit. 25 , 26 Melatonin is also prescribed to assist in withdrawing from hypnotic medications, although a systematic review revealed minimal efficacy. 27 There is currently much interest in the use of melatonin for treating the sleep-related symptoms of neurodegenerative diseases and even potentially to prevent their development, though there is limited evidence for this at present.…”