A two-part, double-blind, placebo-controlled trial of exogenous melatonin in REM sleep behaviour disorder

Abstract

SUMMAR Y Rapid eye movement (REM) sleep behaviour disorder (RBD) has been suggested to predict the development of neurodegenerative disorders. Patients with RBD are acting out dream behaviour associated with loss of normal muscle atonia of REM sleep. The aim of the present study was to confirm that exogenous melatonin improves RBD. Eight consecutively recruited males (mean age 54 years) with a polysomnographically (PSG) confirmed diagnosis of RBD were included in a two-part, randomized, doubleblind, placebo-controlled cross-over study. Patients received placebo and 3 mg of melatonin daily in a cross-over design, administered between 22:00 h and 23:00 h over a period of 4 weeks. PSG recordings were performed in all patients at baseline, at the end of Part I of the trial and at the end of Part II of the trial. Compared to baseline, melatonin significantly reduced the number of 30-s REM sleep epochs without muscle atonia (39% versus 27%; P = 0.012), and led to a significant improvement in clinical global impression (CGI: 6.1 versus 4.6; P = 0.024). Interestingly, the number of REM sleep epochs without muscle atonia remained lower in patients who took placebo during Part II after having received melatonin in Part I (-16% compared to baseline; P = 0.043). In contrast, patients who took placebo during Part I showed improvements in REM sleep muscle atonia only during Part II (i.e. during melatonin treatment). The data suggest that melatonin might be a second useful agent besides clonazepam in the treatment of RBD.k e y w o r d s chronobiotic, circadian rhythms, lewy body dementia, melatonin, neurodegenerative disorder, rem sleep behaviour disorder, rbd, sleep disorders

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

“…RBD is often the first indication of an impending α‐synuclein disorder, such as Parkinson's disease, multiple‐system atrophy, or dementia with Lewy bodies (Howell and Schenck, 2015). There is emerging evidence that treatment with melatonin effectively improves the clinical and neurophysiological aspects of RBD, especially elderly individuals with underlying neurodegenerative disorders (Kunz and Mahlberg, 2010). Because RBD is a prodromal syndrome of Parkinson's disease (or related disorders), it represents a unique opportunity for testing the disease‐modifying potential of melatonin therapy.…”

Beneficial Effects of Ramelteon on Rapid Eye Movement Sleep Behavior Disorder Associated with Parkinson's Disease - Results of a Multicenter Open Trial

“…Because the striatal dopamine circuit also regulates sleep quality (30), increased striatal L-dopa bioavailability by melatonin may modulate sleep in patients with PD. In terms of clinical studies, four reports of studies using polysomnography (PSG) have described that melatonin decreases RWA (6)(7)(8)(9). Furthermore, compared with clonazepam, melatonin may significantly lessen the risk of falls and injury in patients with PD (10).…”

“…Because melatonin and ramelteon have relatively few adverse side effects, they have both proven useful in the elderly population, especially in patients with neurological disorders (5). To date, only one randomized controlled trial has reported beneficial effects of melatonin on RBD (6). Several open and retrospective trials (7)(8)(9)(10)(11) have also suggested that melatonin has beneficial effects on idiopathic and/or secondary RBD.…”

Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders

“…Melatonin facilitates achieving better sleep for these patients by reducing the sleep-onset latency [73] or by regulating sleep-wake times to coincide with the natural circulatory cycle, as well as reducing sleep episodes without muscle atonia. [50] The mechanism by which the occurrence of reducing sleep episodes without muscle atonia in RBD is still unknown and requires further study.…”

“…Participants unsuitable (n= 5) [26][27][28][29][30] Insufficient data for analysis (n= 2) [31,32] Inappropriate method and data collection (n= 4) [33][34][35][36] No clear comparison group (n= 4) [37][38][39][40] Number of studies included in review (n=13) [41][42][43][44][45][46][47][48][49][50][51][52] Publications handpicked (screening reference list) (n= 2) …”