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

Sleep Med. 2015 Jan;16(1):19-26. doi: 10.1016/j.sleep.2014.09.011. Epub 2014 Oct 13.


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.

Keywords: Calmodulin; Drug therapy; Melatonin; Parasomnia; REM sleep behavior disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Central Nervous System Depressants / pharmacology
  • Central Nervous System Depressants / therapeutic use*
  • Humans
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • REM Sleep Behavior Disorder / drug therapy*
  • REM Sleep Behavior Disorder / physiopathology
  • Treatment Outcome


  • Central Nervous System Depressants
  • Melatonin