Melatonin as a treatment after Traumatic Brain Injury: A systematic review and meta-analysis of the pre-clinical and clinical literature.
J Neurotrauma. 2018 Jun 14. Epub 2018 Jun 14. PMID: 29901413
Traumatic brain injury is common and yet effective treatments of the secondary brain injury are scarce. Melatonin is a potent, non-selective neuroprotective and anti-inflammatory agent that is showing promising results in neonatal brain injury. The aim of this study was to systematically evaluate the pre-clinical and clinical literature for the effectiveness of Melatonin to improve outcome after TBI. Using the systematic review protocol for animal intervention studies (SYRCLE) and Cochrane methodology for clinical studies, a search of English articles was performed. Eligible studies were identified and data was extracted. Quality assessment was performed using the SYRCLE risk of bias tool. Meta-analyses were performed using standardized mean differences (SMD). Seventeen studies (15 pre-clinical, 2 clinical) met inclusion criteria. There was heterogeneity in the studies, and all had moderate-to-low risk of bias. Meta-analysis of pre-clinical data revealed an overall positive effect on neurobehavioural outcome with SMD of 1.51 (95% CIs: 1.06-1.96). Melatonin treatment had a favorable effect on the neurological status, by a SMD of 1.35 (95% CI: 0.83-1.88) and cognition by a SMD of 1.16 (95% CIs: 0.4-1.92). Melatonin decreased the size of the contusion by a SMD of 2.22 (95% CI: 0.84-3.59) and cerebral oedema by SMD of 1.91 (95% CI: 1.08-2.74). Only two clinical studies were identified. They were of low quality, used for symptom management, and were of uncertain significance. In conclusion, there is evidence that Melatonin treatment after TBI significantly improves both behavioural outcomes and pathological outcomes, but significant research gaps exist especially in clinical populations. Key Words: Traumatic Brain Injury, Melatonin, Systematic Review.