A placebo-controlled randomized clinical trial of amantadine hydrochloride for evaluating the functional improvement of patients following severe acute traumatic brain injury.

Background Considering the known derangements in the dopaminergic neurotransmitter systems following traumatic brain injury (TBI), dopamine agonists are used as a pharmacologic option. In this study, we evaluate the effects of Amantadine Hydrochloride on the functional improvement of severe TBI patients. Methods Within a triple-blinded (patients, intervention administrators, and outcome assessors) placebo-controlled randomized clinical trial, we evaluated the effects of Amantadine (100mg BD (twice a day) for 14 days, then 150mg BD for another 7 days, and 200mg BD for another 21 days) on outcome measurements of weekly mean Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS), through six weeks of trial for 57 patients (29 Amantadine, 28 placeboes) with severe TBI admitted in our hospital. Results Although both groups had improvement in their DRS, the change from baseline was significantly better in the Amantadine group (10.88 ± 5.24 for Amantadine vs. 8.04 ± 4.07 for placebo, p = 0.015). No significant difference was observed between groups for GOS (1.04 ± 0.55 for Amantadine vs. 1.12 ± 1.05 for placebo, P = 0.966). Conclusions Based on our findings, Amantadine Hydrochloride might improve the speed of functional ability improvement in severe TBI patients, evaluated by DRS, and is also well tolerated by patients. Although, there were some limitations in this study, including small sample size, short time interval, not providing a wash-off period and invalidity of GOS for measuring recovery rates in short-term periods.