Melatonin Therapy of RBD
Rapid eye movement sleep behavior disorder (RBD) has two recommended Level B pharmacotherapies, according to the Best Practice Guide published by the American Academy of Sleep Medicine: clonazepam and melatonin. Melatonin, the focus of this chapter, manifests a gradual effect on RBD over weeks and lacks significant side effects. Amelioration of RBD symptoms with melatonin has been shown to outlast the time of treatment for weeks and sometimes months. Thus, melatonin treatment in RBD patients may be more than just a symptomatic aid. We summarize our center’s experience over the last 20 years and other published data on the treatment of RBD patients with melatonin. Compared to clonazepam therapy of RBD, outcome data with melatonin therapy of RBD have been reported in far fewer patients. We cite evidence for our hypothesis that one basic mode of melatonin’s therapeutic action on RBD symptoms involves the strengthening influence via the circadian timing system. Clearly, no circadian abnormality has been proven in RBD patients as yet. However, RBD is being considered as a prodromal of neurodegenerative synucleinopathies like Parkinson’s, which are mostly accompanied by a substantial breakdown of the circadian system. Melatonin is a chronobiotic, and REM sleep is under the strongest circadian influence compared to other sleep stages. We assume that restoration of the circadian timing system integrity by melatonin in the early phase before conversion to a full-blown synucleinopathy will lead, mainly via the MT1 receptor, to an improvement of the timely orchestration and integrity of all processes necessary for a proper functioning of REM sleep, which in turn would alleviate RBD. Confirmation of this hypothesis doubtlessly awaits a substantial amount of future research.
KeywordsREM sleep behavior disorder (RBD) Melatonin Melatonergic agonists Circadian rhythm Synucleinopathy Neurodegenerative disease
We thank our patients for the continuing trust they put in us. Many of the diagnostics and treatments suggested were experimental. We thank Katharina Grohme for her participation in writing and editing of an earlier version of the manuscript. We also thank Prof. Daniel P. Cardinali for critically reviewing our manuscript.
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