Primary Objective: To evaluate the effects of administering Donepezil during inpatient rehabilitation for individuals with TBI.

Research Design: Retrospective, age and injury severity matched, mixed between-within subjects analysis.

Methods And Procedures: Thirty-six patients with moderate-to-severe TBI admitted to acute rehabilitation within 90 days of injury. Main outcome measures included FIM cognitive total scores and rehabilitation lengths of stay.

Intervention: Initiation of Donepezil administration beginning at 5 mg daily. Dose titration and continuation based on perceived clinical response.

Main Outcomes And Results: No differences in cognitive improvement were observed between the Donepezil treatment group and the matched control group. Sub-set analyses suggested that administration of Donepezil early in the rehabilitation stay was significantly related to higher rates of cognitive improvement.

Conclusions: Preliminary evidence suggests that Donepezil administration early in the rehabilitation stay may have advantageous treatment effects. A prospective, randomized, placebo-controlled clinical trial with standard timing, dosage and treatment duration is recommended to further evaluate treatment efficacy.

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