Open-label study of donepezil in traumatic brain injury

Objective: To determine preliminarily whether donepezil will improve memory, behavior, and global function after chronic traumatic brain injury (TBI). Design: Sixteen-week open-label study. Setting: Outpatient TBI rehabilitation program. Patients: Four patients with chronic, severe TBI. Interventions: Donepezil 5mg daily for 8 weeks followed by 10mg daily for 4 weeks. Main Outcome Measures: Memory measures included the Rey Auditory Verbal Learning Test (RAVLT), the Complex Figure Test (CFT), items from the Rivermead Behavioural Memory Test (RBMT), and a semantic fluency task. The Neuropsychiatric Inventory (NPI) evaluated behavior and affect. Function was assessed by using the FIM(TM) instrument and a clinical global impression of change. Results: On the RAVLT, the mean scores for learning and short- and long-term recall improved by 0.4, 1.04, and .83 standard deviations (SDs) above baseline respectively. On the CFT, the mean scores for short-term recall and long-term recall improved by 1.56 and 1.38 SDs above baseline, respectively. A positive trend was observed on the RBMT and on the NPI subscales. Conclusions: Donepezil may improve some aspects of memory and behavior in persons with chronic TBI. Randomized clinical trials are required to support these preliminary findings.