Amantadine Use in Severe Traumatic Brain Injury

Amantadine, a weak noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with dopaminergic activity, has emerged as a promising adjunctive therapy in the management of traumatic brain injury (TBI), particularly in patients with disorders of consciousness. Although historically utilized for the treatment of Influenza A and Parkinson's disease, growing evidence supports its role in promoting neurocognitive recovery following TBI. This review synthesizes preclinical and clinical literature evaluating the pharmacologic mechanisms, therapeutic efficacy, dosing strategies, and safety profile of amantadine in TBI. Clinical trials demonstrate accelerated recovery of consciousness and improved functional outcomes, particularly during the subacute phase of injury. Despite demonstrated benefits and generally favorable safety profile, significant heterogeneity exists in patient selection, dosing and treatment duration, and the standardization of treatment algorithms. This review serves to consolidate the current evidence base, clarify the mechanistic rationale for amantadine use in TBI, and provide a clinically grounded framework to guide its responsible and effective application within the context of neurological rehabilitation.