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Sleep and circadian rhythm disturbances following traumatic brain injury: the treatment and efficacy of melatonin supplementation
thesisposted on 21.02.2017, 02:39 by Grima, Natalie Ann
Traumatic brain injury (TBI) is a leading cause of ongoing disability in young and old people worldwide. Improvements in the acute management of TBI have resulted in a reduction in mortality rates, and this has led to a growth in the population of TBI patients. Although a large majority of TBI patients generally make a good physical recovery, outcome studies indicate that sleep disturbance is a common problem, with over 50% of those with moderate-to-severe TBI exhibiting difficulties years post injury. Disrupted sleep can often go untreated, impacting quality of life, contributing to ongoing cognitive dysfunction, as well as impeding rehabilitation and return to pre-injury activities. Evidence-based treatments are lacking, partly due to poor understanding of the pathophysiological mechanisms underpinning sleep disturbances following TBI. As such, this thesis aimed to: 1) Elucidate and characterise the objective and subjective sleep complaints following TBI relative to healthy controls, 2) Understand the roles of melatonin and circadian rhythms in the development of sleep disturbances and 3) Investigate the clinical efficacy and safety of melatonin supplementation to alleviate sleep disturbances following TBI. By way of a systematic literature search and meta-analysis, the current thesis examined objective and subjective sleep complaints in patients with TBI compared to healthy controls. This meta-analysis found that individuals with TBI experienced objectively shorter total sleep durations, increased wake after sleep onset and poorer sleep efficiency. Furthermore people with TBI reported greater subjective sleepiness and poorer perceived sleep quality. To investigate potential pathophysiological mechanisms underpinning sleep disturbances in individuals with TBI diagnosed with chronic insomnia, this thesis compared overnight salivary melatonin concentrations in patients with TBI with those of age- and gender-matched controls. This study found that overnight salivary melatonin concentrations were reduced by 42% in patients with TBI relative to controls. Furthermore, the timing of melatonin was delayed in patients with TBI and delayed melatonin onset was associated with poorer subjective sleep quality. In light of these findings, the current thesis examined the efficacy of exogenous melatonin supplementation in alleviating sleep disturbances in TBI patients diagnosed with chronic insomnia. By conducting a randomised, placebo-controlled, crossover clinical trial, the current thesis demonstrated that four weeks of melatonin supplementation significantly improved sleep quality and sleep efficiency as measured by the Pittsburgh sleep quality index and actigraphy, respectively. Additionally, a trend suggested that melatonin supplementation reduced actigraphic sleep onset latency. No improvements in daytime sleepiness were observed following melatonin supplementation. The findings of the current thesis are pertinent to the treatment and management of sleep complaints in individuals exhibiting sleep problems following TBI. Firstly, the current thesis corroborates subjective sleep complaints with objective measures of sleep quality. Secondly, the thesis suggests that reduced melatonin production and circadian misalignment may contribute to sleep disturbances in patients with TBI diagnosed with chronic insomnia. Finally, the current thesis provides evidence- to support the use of melatonin supplementation in alleviating chronic insomnia symptomatology following TBI.