Poorer sleep quality predicts melatonin response in patients with traumatic brain injury: findings from a randomized controlled trial

Abstract

Study objectives: A recent clinical trial demonstrated that melatonin treatment was effective in improving self-perceived sleep quality in patients with traumatic brain injury (TBI); however, it remains unclear which patients benefited from melatonin treatment. To that end, findings from the clinical trial were re-examined to identify possible predictors of treatment response.

Methods: Hierarchical multiple regression was used to identify patient characteristics, TBI injury characteristics, and self-report measures assessing sleep, fatigue, mood, and anxiety symptomatology that may uniquely explain a change in self-reported sleep quality scores (follow-up minus baseline score) as assessed by the Pittsburgh Sleep Quality Index (PSQI).

Results: After controlling for patient demographic and TBI injury-related variables, baseline self-report measures of sleep, fatigue, mood, and anxiety explained an additional 32% of the variance in change in PSQI scores. However, only baseline PSQI score made a unique and statistically significant contribution (β = -0.56, P = .006). After controlling for patient and TBI characteristics, baseline PSQI scores further explained 27% of the variance in change in PSQI scores (R² change = .27, F_{1, 27} change = 11.79, P = .002). The standardized β for baseline PSQI score revealed a statistically significant negative relationship with change in PSQI score (β = -0.54, P = .002), revealing that higher PSQI score at baseline was associated with better sleep outcomes.

Conclusions: In a sample comprising predominantly severe TBI and comorbid insomnia, participants who report poorer sleep quality have the most to gain from melatonin treatment irrespective of time since injury, demographics, fatigue, daytimes sleepiness, mood, and anxiety symptomology.

Clinical trial registration: Registry: Australian New Zealand Clinical Trials Registry; Name: Efficacy of Melatonin for Sleep Disturbance Following Traumatic Brain Injury; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=343083&showOriginal=true&isReview=true; Identifier: ACTRN12611000734965.

Citation: 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(8):1545-1551.

Keywords: acquired brain injury; insomnia; melatonin; sleep disturbance; traumatic brain injury.