Pilot Randomized Trial of Donepezil Hydrochloride for Delirium After Hip Fracture.

Objectives To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair. Design Pilot double-masked randomized placebo-controlled trial. Setting Large academic medical center. Participants Sixteen individuals aged 70 and older with hip fracture. Intervention Donepezil 5 mg or placebo was randomly allocated and initiated within 24 hours of surgery, preoperatively or postoperatively. Daily treatment was continued for 30 days or until side effects or the clinical situation required termination. Measurements All outcomes were ascertained masked to treatment status. Information on drug tolerability and safety was obtained from the participant, nurse, and medical record. Delirium presence and severity were measured during daily hospital interviews and at 2, 4, and 6 weeks after surgery after a standardized assessment using the Confusion Assessment Method ( CAM) and the Memorial Delirium Assessment Scale ( MDAS). Results Participants in the donepezil and placebo arms had similar baseline characteristics. Participants in the donepezil arm experienced significantly more side effects. In longitudinal models, there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time (odds ratio = 0.9, 95% confidence interval ( CI) = 0.4-2.3) or delirium severity over time (effect size = −0.2 on 30-point MDAS scale, 95% CI = −1.5-1.2). Conclusion Participants randomized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects. Overall, sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial. [ABSTRACT FROM AUTHOR]