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

  • Maree Cassimatis
    Affiliations
    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
    Affiliations
    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
    Correspondence
    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.
    Affiliations
    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:https://doi.org/10.1016/j.apmr.2022.09.018

      Abstract

      Objective

      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.

      Conclusion

      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.

      Keywords

      List of abbreviations:

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

        • Dewan MC
        • Rattani A
        • Gupta S
        • et al.
        Estimating the global incidence of traumatic brain injury.
        J Neurosurg. 2019; 130: 1080-1097
        • Howlett JR
        • Nelson LD
        • Stein MB.
        Mental health consequences of traumatic brain injury.
        Biol Psychiatry. 2022; 91: 413-420
        • Zhou Y
        • Greenwald BD.
        Update on insomnia after mild traumatic brain injury.
        Brain Sci. 2018; 8: 223
        • Morse AM
        • Garner DR.
        Traumatic brain injury, sleep disorders, and psychiatric disorders: an underrecognized relationship.
        Med Sci (Basel). 2018; 6: 15
        • Lucke-Wold BP
        • Smith KE
        • Nguyen L
        • et al.
        Sleep disruption and the sequelae associated with traumatic brain injury.
        Neurosci Biobehav Rev. 2015; 55: 68-77
        • Botchway EN
        • Godfrey C
        • Anderson V
        • Catroppa C.
        A systematic review of sleep-wake disturbances in childhood traumatic brain injury: relationship with fatigue, depression, and quality of life.
        J Head Trauma Rehabil. 2019; 34: 241-256
        • Mathias JL
        • Alvaro PK.
        Prevalence of sleep disturbances, disorders, and problems following traumatic brain injury: a meta-analysis.
        Sleep Med. 2012; 13: 898-905
        • Gagner C
        • Landry-Roy C
        • Lainé F
        • Beauchamp MH.
        Sleep-wake disturbances and fatigue after pediatric traumatic brain injury: a systematic review of the literature.
        J Neurotrauma. 2015; 32: 1539-1552
        • Mollayeva T
        • Colantonio A
        • Mollayeva S
        • Shapiro CM.
        Screening for sleep dysfunction after traumatic brain injury.
        Sleep Med. 2013; 14: 1235-1246
        • Sandsmark DK
        • Elliott JE
        • Lim MM.
        Sleep-wake disturbances after traumatic brain injury: synthesis of human and animal studies.
        Sleep. 2017; 40 (zsx044)
        • Grima N
        • Ponsford J
        • Rajaratnam SM
        • Mansfield D
        • Pase MP.
        Sleep disturbances in traumatic brain injury: a meta-analysis.
        J Clin Sleep Med. 2016; 12: 419-428
        • Ouellet MC
        • Beaulieu-Bonneau S
        • Morin CM.
        Insomnia in patients with traumatic brain injury: frequency, characteristics, and risk factors.
        J Head Trauma Rehabil. 2006; 21: 199-212
        • Montgomery MC
        • Baylan S
        • Gardani M.
        Prevalence of insomnia and insomnia symptoms following mild-traumatic brain injury: a systematic review and meta-analysis.
        Sleep Med Rev. 2022; 61101563
        • Shekleton JA
        • Parcell DL
        • Redman JR
        • Phipps-Nelson J
        • Ponsford JL
        • Rajaratnam SMW.
        Sleep disturbance and melatonin levels following traumatic brain injury.
        Neurology. 2010; 74: 1732-1738
        • Amaral FGD
        • Cipolla-Neto J.
        A brief review about melatonin, a pineal hormone.
        Arch Endocrinol Metab. 2018; 62: 472-479
        • Dudley KA
        • Patel SR.
        Sleep disorders and melatonin.
        in: Redline S Berger NA Impact of sleep and sleep disturbances on obesity and cancer. Springer, New York2014: 51-76
        • Foley HM
        • Steel AE.
        Adverse events associated with oral administration of melatonin: a critical systematic review of clinical evidence.
        Complement Ther Med. 2019; 42: 65-81
        • Wei S
        • Smits MG
        • Tang X
        • et al.
        Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials.
        Sleep Med. 2020; 68: 1-8
        • Elbin RJ
        • Schatz P
        • Lowder HB
        • Kontos AP.
        An empirical review of treatment and rehabilitation approaches used in the acute, sub-acute, and chronic phases of recovery following sports-related concussion.
        Curr Treat Options Neurol. 2014; 16: 320
        • Barlow KM
        • Esser MJ
        • Veidt M
        • Boyd R.
        Melatonin as a treatment after traumatic brain injury: a systematic review and meta-analysis of the pre-clinical and clinical literature.
        J Neurotrauma. 2019; 36: 523-537
        • Ludwig R
        • Vaduvathiriyan P
        • Siengsukon C.
        Does cognitive-behavioural therapy improve sleep outcomes in individuals with traumatic brain injury: a scoping review.
        Brain Inj. 2020; 34: 1569-1578
        • Bogdanov S
        • Naismith S
        • Lah S.
        Sleep outcomes following sleep-hygiene-related interventions for individuals with traumatic brain injury: a systematic review.
        Brain Inj. 2017; 31: 422-433
        • Thomas A
        • Greenwald BD.
        Nonpharmacological management of sleep disturbances after traumatic brain injury.
        NeuroRehabilitation. 2018; 43: 355-360
        • Lowe A
        • Bailey M
        • O'Shaughnessy T
        • Macavei V
        Treatment of sleep disturbance following stroke and traumatic brain injury: a systematic review of conservative interventions.
        Disabil Rehabil. 2022; 44: 2975-2987
        • Tricco AC
        • Lillie E
        • Zarin W
        • et al.
        PRISMA extension for scoping reviews (PRISMA-ScR): checklist and explanation.
        Ann Intern Med. 2018; 169: 467-473
        • Page MS
        • Berger AM
        • Johnson LB.
        Putting evidence into practice: evidence-based interventions for sleep-wake disturbances.
        Clin J Oncol Nurs. 2006; 10: 753-767
      1. Australian Institute of Health and Welfare. Australia's health 2018. Canberra (ACT). Available at: https://www.aihw.gov.au/getmedia/7c42913d-295f-4bc9-9c24-4e44eff4a04a/aihw-aus-221.pdf.aspx?inline=true. Accessed June 20, 2018.

        • Rissman R
        • Zimmer Rissman B
        • Compliance I
        Noncompliance: a review. II. Facilitating compliance.
        Fam Syst Med. 1987; 5: 446-467
        • Downs SH
        • Black N.
        The feasibility of creating a checklist for the assessment of the methodological quality both of randomised and non-randomised studies of health care interventions.
        J Epidemiol Community Health. 1998; 52: 377-384
        • O'Connor SR
        • Tully MA
        • Ryan B
        • Bradley JM
        • Baxter GD
        • McDonough SM.
        Failure of a numerical quality assessment scale to identify potential risk of bias in a systematic review: a comparison study.
        BMC Res Notes. 2015; 8: 224
        • Pengelly J
        • Pengelly M
        • Lin KY
        • et al.
        Exercise parameters and outcome measures used in cardiac rehabilitation programs following median sternotomy in the elderly: a systematic review and meta-analysis.
        Heart Lung Circ. 2019; 28: 1560-1570
        • Hooper P
        • Jutai JW
        • Strong G
        • Russell-Minda E.
        Age-related macular degeneration and low-vision rehabilitation: a systematic review.
        Can J Ophthalmol. 2008; 43: 180-187
        • Anand S
        • Tong H
        • Besag FMC
        • Chan EW
        • Cortese S
        • Wong ICK
        Safety, tolerability and efficacy of drugs for treating behavioural insomnia in children with attention-deficit/hyperactivity disorder: a systematic review with methodological quality assessment.
        Paediatr Drugs. 2017; 19: 235-250
        • Barlow KM
        • Kirk V
        • Brooks B
        • et al.
        Efficacy of melatonin for sleep disturbance in children with persistent post-concussion symptoms: secondary analysis of a randomized controlled trial.
        J Neurotrauma. 2021; 38: 950-959
        • Grima NA
        • Rajaratnam SMW
        • Mansfield D
        • McKenzie D
        • Ponsford JL.
        Poorer sleep quality predicts melatonin response in patients with traumatic brain injury: findings from a randomized controlled trial.
        J Clin Sleep Med. 2021; 17: 1545-1551
        • Grima NA
        • Rajaratnam SMW
        • Mansfield D
        • Sletten TL
        • Spitz G
        • Ponsford JL.
        Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial.
        BMC Med. 2018; 16
        • Bramley H
        • Henson A
        • Lewis MM
        • Kong L
        • Stetter C
        • Silvis M.
        Sleep disturbance following concussion is a risk factor for a prolonged recovery.
        Clin Pediatr. 2017; 56: 1280-1285
        • Lequerica A
        • Jasey N
        • Portelli Tremont JN
        • Chiaravalloti ND
        Pilot study on the effect of Ramelteon on sleep disturbance after traumatic brain injury: preliminary evidence from a clinical trial.
        Arch Phys Med Rehabil. 2015; 96: 1802-1809
        • Carter KA
        • Lettieri CJ
        • Peńa JM.
        An unusual cause of insomnia following IED-induced traumatic brain injury.
        J Clin Sleep Med. 2010; 6: 205-206
        • Kemp S
        • Biswas R
        • Neumann V
        • Coughlan A.
        The value of melatonin for sleep disorders occurring post-head injury: a pilot RCT.
        Brain Inj. 2004; 18: 911-919
        • Dagan Y
        • Abadi J.
        Sleep-wake schedule disorder disability: a lifelong untreatable pathology of the circadian time structure.
        Chronobiol Int. 2001; 18: 1019-1027
        • Nagtegaal JE
        • Kerkhof GA
        • Smits MG
        • Swart AC
        • van der Meer YG.
        Traumatic brain injury-associated delayed sleep phase syndrome.
        Funct Neurol. 1997; 12: 345-348
        • Brzezinski A
        • Vangel MG
        • Wurtman RJ
        • et al.
        Effects of exogenous melatonin on sleep: a meta-analysis.
        Sleep Med Rev. 2005; 9: 41-50
        • Xie Z
        • Chen F
        • Li WA
        • et al.
        A review of sleep disorders and melatonin.
        Neurol Res. 2017; 39: 559-565
        • Li T
        • Jiang S
        • Han M
        • et al.
        Exogenous melatonin as a treatment for secondary sleep disorders: a systematic review and meta-analysis.
        Front Neuroendocrinol. 2019; 52: 22-28
        • Kuriyama A
        • Honda M
        • Hayashino Y.
        Ramelteon for the treatment of insomnia in adults: a systematic review and meta-analysis.
        Sleep Med. 2014; 15: 385-392
        • Auld F
        • Maschauer EL
        • Morrison I
        • Skene DJ
        • Riha RL.
        Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders.
        Sleep Med Rev. 2017; 34: 10-22
        • Ahmadi Z
        • Ashrafizadeh M.
        Melatonin as a potential modulator of Nrf2.
        Fundam Clin Pharmacol. 2020; 34: 11-19
        • Reiter RJ
        • Mayo JC
        • Tan DX
        • Sainz RM
        • Alatorre-Jimenez M
        • Qin L
        Melatonin as an antioxidant: under promises but over delivers.
        J Pineal Res. 2016; 61: 253-278
        • Orff HJ
        • Ayalon L
        • Drummond SPA.
        Traumatic brain injury and sleep disturbance: a review of current research.
        J Head Trauma Rehabil. 2009; 24: 155-165
        • Ouellet MC
        • Beaulieu-Bonneau S
        • Morin CM.
        Sleep following traumatic brain injury.
        in: Pandi-Perumal SR Kramer M Sleep and mental illness. Cambridge University Press, Cambridge2010: 353-367
        • Mosti C
        • Spiers MV
        • Kloss JD.
        A practical guide to evaluating sleep disturbance in concussion patients.
        Neurol Clin Pract. 2016; 6: 129-137
        • Cassimatis M
        • Orr R
        • Fyffe A
        • Browne G.
        Association of sleep disturbance with neurocognition, symptom severity, and recovery in paediatric concussion: a 10-year retrospective analysis of a tertiary referral concussion clinic.
        J Head Trauma Rehabil. 2022 Jul 21; ([Epub ahead of print])