Review ArticleMelatonin therapy for REM sleep behavior disorder: a critical review of evidence

•Melatonin can reduce rapid eye movement (REM) sleep without atonia in REM sleep behavior disorder (RBD).•Melatonin doses of 3-12 mg appear efficacious in reducing clinical RBD symptoms.•Minimal side effects may favor melatonin over clonazepam as initial therapy in RBD.•More placebo-controlled and active comparator trials are needed to confirm the benefits.

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia associated with dream enactment often involving violent or potentially injurious behaviors during REM sleep that is strongly associated with synucleinopathy neurodegeneration. Clonazepam has long been suggested as the first-line treatment option for RBD. However, evidence supporting melatonin therapy is expanding. Melatonin appears to be beneficial for the management of RBD with reductions in clinical behavioral outcomes and decrease in muscle tonicity during REM sleep. Melatonin also has a favorable safety and tolerability profile over clonazepam with limited potential for drug-drug interactions, an important consideration especially in elderly individuals with RBD receiving polypharmacy. Prospective clinical trials are necessary to establish the evidence basis for melatonin and clonazepam as RBD therapies.