Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials

Neurol Sci. 2016 Jan;37(1):57-65. doi: 10.1007/s10072-015-2357-0. Epub 2015 Aug 9.


The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.

Keywords: Alzheimer disease; Melatonin; Neurodegenerative diseases; Parkinson disease; REM sleep behavior disorder; Sleep.

Publication types

  • Meta-Analysis

MeSH terms

  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use*
  • Melatonin / adverse effects
  • Melatonin / therapeutic use*
  • Neurodegenerative Diseases / complications*
  • Neurodegenerative Diseases / drug therapy
  • Randomized Controlled Trials as Topic
  • Sleep Wake Disorders / complications*
  • Sleep Wake Disorders / drug therapy*


  • Hypnotics and Sedatives
  • Melatonin