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

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. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00415-020-10353-0) contains supplementary material, which is available to authorized users.