Amantadine for functional improvement in patients with traumatic brain injury: A systematic review with meta-analysis and trial sequential analysis.

Introduction: TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. Research question: Does Amantadine have an effect on functional improvement of TBI patients? Material and methods: This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores. Results: Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores. Discussion and conclusion: Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.