The online version of this article (doi:https://doi.org/10.1186/s12916-017-0995-1) contains supplementary material, which is available to authorized users.
The study aimed to determine the efficacy of melatonin supplementation for sleep disturbances in patients with traumatic brain injury (TBI).
This is a randomised double-blind placebo-controlled two-period two-treatment (melatonin and placebo) crossover study. Outpatients were recruited from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years, standard deviation 11 years; 67% men). They were given prolonged-release melatonin formulation (2 mg; Circadin®) and placebo capsules for 4 weeks each in a counterbalanced fashion separated by a 48-hour washout period. Treatment was taken nightly 2 hours before bedtime. Serious adverse events and side-effects were monitored.
Melatonin supplementation significantly reduced global Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference -1.79; 95% confidence interval (CI), -2.70 to -0.88; p ≤ 0.0001]. Melatonin had no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units; difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and vitality and mental health on the SF-36 v1 questionnaire (p ≤ 0.05 for each). Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue on the Fatigue Severity Scale (p ≤ 0.05 for both), but had no significant effect on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious adverse events were reported.
Melatonin supplementation over a 4-week period is effective and safe in improving subjective sleep quality as well as some aspects of objective sleep quality in patients with TBI.
Identifier: 12611000734965; Prospectively registered on 13 July 2011.
Additional file 1: Table S1. Frequency of symptoms for placebo and melatonin treatments. (DOCX 16 kb)12916_2017_995_MOESM1_ESM.docx
American Academy of Sleep Medicine. International classification of sleep disorders. 3rd ed. Darien: American Academy of Sleep Medicine; 2014.
American Academy of Sleep Medicine. International classification of sleep disorders, revised: diagnostic and coding manual. Chicago: American Academy of Sleep Medicine; 2001.
Garkinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet. 1995;346(8974):541–4.
Wade AG, Ford I, Crawford G, McConnachie A, Nir T, Laudon M, Zisapel N. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BioMed Central Med. 2010;8.
Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16(4):372–80.
Sinclair KL, Ponsford JL, Rajaratnam SMW. Actigraphic assessment of sleep disturbances following traumatic brain injury. Behav Sleep Med. 2012.
Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP. The role of actigraphy in the study of sleep and circadian rhythms. Sleep. 2003;26(3):342–92.
Department of Health and Ageing, Therapeutic Goods Administration. Australian public assessment report for melatonin: circadin. Canberra: Australian Government; 2011. Online access: https://www.tga.gov.au/sites/default/files/auspar-circadin-110118.pdf.
Spong J, Kennedy GA, Brown Jr RD, Armstrong BG, Berlowitz D. Melatonin supplementation in patients with complete tetraplegia and poor sleep. Sleep Disord. 2013;2013(128197):1-8.
Zeitzer JM, Ayas NT, Shea SA, Brown R, Czeisler CA. Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia. J Clin Endocrinol Metab. 2000;85(6):2189–96. PubMed
Shochat T, Luboshitzky R, Lavie P. Nocturnal melatonin onset is phase locked to the primary sleep gate. Am J Physiol. 1997;273(1 Pt 2):R364–70. PubMed
Lavie P. Melatonin: role in gating nocturnal rise in sleep propensity. J Biol Rhythm. 1997;12(6):657–65. CrossRef
Rajaratnam SMW, Cohen DA, Rogers NL. Melatonin and melatonin analogues. Sleep Med Clin. 2009;4(2):179–93. CrossRef
Cagnacci A, Elliott JA, Yen SSC. Melatonin: a major regulator of the circadian rhythm of core temperature in humans. J Clin Endocrinol Metab. 1992;75:447–52. PubMed
Rogers NL, Dinges DF, Kennaway DJ, Dawson D. Potential action of melatonin in insomnia. Sleep. 2003;26(8):1058–9. PubMed
Pierrefiche G, Zerbib R, Laborit H. Anxiolytic activity of melatonin in mice: involvement of benzodiazepine receptors. Res Commun Chem Pathol Pharmacol. 1993;82(2):131–42. PubMed
Department of Health and Ageing, Therapeutic goods administration. Australian Public Assessment Report for Melatonin. In: Australian Government. 2009. p. 42–53.
Larson EB, Zollman FS. The effect of sleep medications on cognitive recovery from traumatic brain injury. J Head Trauma Rehabil. 2010;25(1):61–7.
Nguyen S, McKay A, Wong D, Rajaratnam SMW, Spitz G, Williams G, et al. Cognitive behavior therapy to treat sleep disturbance and fatigue after traumatic brain injury: a pilot randomized controlled trial. Arch Phys Med Rehabil. 2017;98(8):1508–1517.e1502.
- Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial
Natalie A. Grima
Shantha M. W. Rajaratnam
Tracey L. Sletten
Jennie L. Ponsford
- BioMed Central
Neu im Fachgebiet Allgemeinmedizin
Meistgelesene Bücher aus dem Fachgebiet
e.Med Kampagnen-Visual, Mail Icon II