Abstract: There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients. Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury, but relatively less is known about the effect in pediatric populations. The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibitors as a potential adjuvant treatment for neurocognitive decline in pediatric patients with traumatic brain injury. Investigators queried PubMed to identify literature published from database inception through June 2023 describing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions. Based on preselected search criteria, 340 unique papers were selected for title and abstract screening. Thirty-two records were reviewed in full after eliminating preclinical studies and papers outside the scope of the project. In adult traumatic brain injury, we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tolerated and shows both objective and patient-reported efficacy for reducing cognitive impairment. In children, 3 papers report on 5 children recovering from traumatic brain injury, showing limited efficacy. An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group. Given its promise for efficacy in adults with traumatic brain injury and tolerability in pediatric patients, we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Key words: acetylcholinesterase inhibitor, adult, cognition, donepezil, pediatrics, traumatic brain injury