Early Amantadine Treatment in Children with Severe Traumatic Brain Injury: A Dual-Center Cohort Study and Brief Review

Purpose Traumatic brain injury (TBI) is a major public health concern and a leading cause of disability and mortality worldwide. While the acute phase of TBI is characterized by increased dopamine release, long-term alterations in the dopaminergic system often lead to dopamine deficiency. Amantadine, a dopamine agonist and NMDA antagonist, has been suggested as a potential therapeutic agent for cognitive and behavioral impairments in TBI. In pediatric populations, amantadine has been primarily used in the rehabilitation phase; however, its effects during the acute phase remain unclear. This study aimed to evaluate the neurological and systemic outcomes of early amantadine treatment in children with severe TBI. Methods This retrospective study analyzed data from pediatric patients with severe TBI admitted to two centers between 2020 and 2025. Patients were divided into two groups based on whether they received amantadine treatment. The treatment protocol was initiated during the acute phase. Functional outcomes were assessed at intensive care unit discharge (ICU) and six months post-injury. Results A total of 60 patients were included, with 32 receiving amantadine. The median ICU stay was 11 days, and the hospital stay was 20 days. At the six-month follow-up, there was a significant improvement in functional status scores compared to ICU discharge (p < 0.001*), but no significant difference was observed between the amantadine and non-amantadine groups in functional recovery. A strong positive correlation was observed between functional scores and length of hospitalization. Conclusion Early administration of amantadine in pediatric patients with severe TBI did not provide a significant functional benefit. However, it was well tolerated and demonstrated a favorable safety profile.