A critical review of the pharmacological treatment of REM sleep behavior disorder in adults: time for more and larger randomized placebo-controlled trials

Abstract

Rapid Eye Movement sleep behavior disorder (RBD) is a parasomnia causing sufferers to physically act out their dreams. These behaviors can disrupt sleep and sometimes lead to injuries in patients and their bed-partners. Clonazepam and melatonin are the first-line pharmacological treatment options for RBD based on direct uncontrolled clinical observations and very limited double-blind placebo-controlled trials. Given the risk for adverse outcomes, especially in older adults, it is of great importance to assess the existing level of evidence for the use of these treatments. In this update, we therefore critically review the clinical and scientific evidence on the pharmacological management of RBD in people aged over 50. We focus on the first-line treatments, and provide an overview of all other alternative pharmacological agents trialed for RBD we could locate as supplementary materials. By amalgamating all clinical observations, our update shows that 66.7% of 1,026 RBD patients reported improvements from clonazepam and 32.9% of 137 RBD patients reported improvements from melatonin treatment on various outcome measures in published accounts. Recently, however, three relatively small randomized placebo-controlled trials did not find these agents to be superior to placebo. Given clonazepam and melatonin are clinically assumed to majorly modify or eliminate RBD in nearly all patients—there is an urgent need to test whether this magnitude of treatment effect remains intact in larger placebo-controlled trials.

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.…”

“…Given the facts that PD is a very common neurological disorder and RBD is frequently associated with it before the onset of motor symptoms, it seems reasonable studies looking for neuroprotective strategies should include a selection of patients with polysomonographically confirmed iRBD and neurochemical and/or neuroimaging markers that suggest a high-risk of phenoconversion to synucleinopathies [15,91,97,99]. The combination of functional neuroimaging studies using different tracers, transcranial sonography, brain per-fusion and glucose metabolism studies, functional MRI, and the detection of α-synuclein in certain tissues should be useful for this purpose [15].…”

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

“…However, non-motor symptoms like REM Behavior Disorder (RBD) (characterized by the occurrence of vivid, intense, and violent movements during REM sleep) precede the onset of PD for years and are indicators of worse prognosis. Daily administration of 3–12 mg of IR melatonin at bedtime or 2 mg PR melatonin has been shown to be effective in the treatment of RBD ( 30 , 74 , 75 , 81 ).…”

Schlaf und Schlafstörungen im hohen Lebensalter

“…Therapeutisch sollte die Schlafstätte so hergerichtet werden, dass Verletzungen möglichst nicht auftreten können. Pharmakologisch werden Melatonin oder Clonazepam eingesetzt 22 .…”