The Utility of Melatonin for the Treatment of Sleep Disturbance After Traumatic Brain Injury: A Scoping Review

  • Maree Cassimatis
    Discipline of Exercise and Sports Science, Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Sydney, Australia
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  • Gary Browne
    Sydney Children's Hospital Network, Children's Hospital Institute of Sports Medicine, Children's Hospital Westmead, Sydney, Australia

    Discipline of Child and Adolescent Health, Sydney Medical School, The University of Sydney, Sydney, Australia
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  • Rhonda Orr
    Corresponding author Rhonda Orr, PhD, Discipline of Exercise and Sport Science, Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Sydney, New South Wales, 2006, Australia.
    Discipline of Exercise and Sports Science, Faculty of Medicine and Health, Sydney School of Health Sciences, The University of Sydney, Sydney, Australia

    Sydney Children's Hospital Network, Children's Hospital Institute of Sports Medicine, Children's Hospital Westmead, Sydney, Australia
    Search for articles by this author
Published:October 12, 2022DOI:



      To investigate the utility of melatonin supplementation as a treatment option for individuals with sleep disturbance after traumatic brain injury (TBI).

      Data Sources

      A systematic search was conducted in 6 electronic databases (Medline, AMED, CINAHL, Embase, Scopus, and SPORTDiscus) from earliest records to April 2022.

      Study Selection

      Studies were eligible for inclusion if they met the following criteria: a) human participants with sleep disturbance after TBI, b) melatonin or melatonergic agent used as an intervention to treat sleep disturbance, and c) outcomes of melatonin administration reported. All TBI severity types (mild, moderate, and severe) were eligible. The initial search retrieved a total of 595 articles, with 9 studies meeting the eligibility criteria.

      Data Extraction

      Two reviewers independently extracted data from eligible studies and assessed methodological quality. Extracted data consisted of participant and injury characteristics, melatonin interventional properties, and sleep outcome. Methodological quality was assessed via the Downs and Black checklist.

      Data Synthesis

      A total of 251 participants with TBI-induced sleep disturbance (mean age range: 14.0-42.5 years) were included. Melatonin, Circadin (prolonged-release melatonin), or Ramelteon (melatonin receptor agonist) were administered. Dosages and intervention duration ranged from 2 to 10 mg and 3 to 12 weeks, respectively. Eight out of 9 studies reported positive outcomes after melatonin treatment. Significant improvements in subjective sleep quality, objective sleep efficiency, and total sleep time were found with melatonin. Reductions in self-reported fatigue, anxiety, and depressive symptoms were also observed with melatonin treatment. No serious adverse events were reported after melatonin administration.


      Melatonin has good tolerability after short-term use and the potential to be a therapeutic agent for those with sleep disturbance after TBI. Melatonin was shown to be beneficial to sleep quality, sleep duration, and sleep efficiency. Additional clinically relevant outcomes of improved mental health suggest that melatonin use may be a promising treatment option for individuals experiencing co-occurring disorders of mood and sleep disturbance post-injury.


      List of abbreviations:

      RCT (randomized controlled trial), TBI (traumatic brain injury)
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