Melatonin as a Chronobiotic/Cytoprotective Agent in REM Sleep Behavior Disorder.

Area of Science:

• Neurology
• Sleep Medicine
• Neuropharmacology

Background:

• REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment due to lack of muscle paralysis during REM sleep.
• RBD is a significant prodromal marker for α-synucleinopathies, including Parkinson disease, multiple system atrophy, and Lewy body dementia.
• Patients with RBD often develop these neurodegenerative diseases approximately 10 years after diagnosis, offering a critical window for intervention.

Purpose of the Study:

• To review the current applications of melatonin in managing REM sleep behavior disorder.
• To explore the potential of melatonin as a disease-modifying agent in α-synucleinopathies.
• To discuss the therapeutic efficacy of melatonin in preventing the progression of neurodegenerative diseases.

Main Methods:

• Literature review of studies on melatonin's use in RBD and α-synucleinopathies.
• Analysis of melatonin's dual role: symptomatic treatment for RBD and potential neuroprotection.
• Examination of dosing strategies, including standard low doses and higher investigational doses.

Main Results:

• Low-dose melatonin (<10 mg/day) is a common first-line symptomatic treatment for RBD, often alongside clonazepam.
• Higher doses of melatonin, though less commonly used clinically, may possess cytoprotective properties beneficial for halting α-synucleinopathy progression.
• Phase 1 studies indicate melatonin is safe at doses up to 100 mg/day.

Conclusions:

• Melatonin serves a dual purpose in RBD management: symptomatic relief and potential disease modification in associated α-synucleinopathies.
• Further large-scale, double-blind trials are necessary to confirm melatonin's therapeutic efficacy in preventing neurodegeneration.
• Investigating higher melatonin doses warrants consideration for its disease-modifying potential in α-synucleinopathies.