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Randomized Controlled Trial
, 16 (1), 8

Efficacy of Melatonin for Sleep Disturbance Following Traumatic Brain Injury: A Randomised Controlled Trial

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Randomized Controlled Trial

Efficacy of Melatonin for Sleep Disturbance Following Traumatic Brain Injury: A Randomised Controlled Trial

Natalie A Grima et al. BMC Med.

Abstract

Background: The study aimed to determine the efficacy of melatonin supplementation for sleep disturbances in patients with traumatic brain injury (TBI).

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: Identifier: 12611000734965; Prospectively registered on 13 July 2011.

Keywords: Acquired brain injury; Insomnia; Sleep; Traumatic brain injury.

Conflict of interest statement

Ethics approval and consent to participate

The study was prospectively approved by the following ethics committees, and participant consent was obtained from each participant before enrolment into the study as per the guidelines outlined by each of the human research committees: Monash University Human Research Committee (CF11/1900-2011001061), Epworth HealthCare Human Research Committee (52111) and Austin Health Human Research Committee (H2013/04950).

Consent for publication

Not applicable.

Competing interests

All authors have completed the International Committee of Medical Journal Editors uniform disclosure form at www.icmje.org/coi_disclosure.pdf. NAG has nothing to disclose. SMWR reports receiving research support outside of the submitted work from Vanda Pharmaceuticals, Phillips Respironics, Teva Pharmaceuticals, Optalert, Philips Lighting, Tyco Healthcare, Compumedics, Rio Tinto and Shell. SMWR also reports that he is the Director of the Sleep Health Foundation as well as the Program Leader of the Cooperative Research Centre for Alertness, Safety and Productivity. SMWR also serves as an advisory board member for Teva Pharmaceuticals (fees paid to Monash University). DM reports receiving grants outside of the submitted work from Fisher Paykel Pty and Rhinomed Pty. TLS reports she serves as a Project Leader in the Cooperative Research Centre for Alertness, Safety and Productivity. GS and JLP have nothing to disclose.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
Overall patient disposition. A total of 35 participants were randomized to treatment. The final ITT sample size comprised of 33 participants. Abbreviations are as follows: ITT intention-to-treat, PSQI Pittsburgh Sleep Quality Index, TBI traumatic brain injury

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