A randomized, double‐blind, placebo‐controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement

Abstract

Objectives This was a pilot, phase 2a study to assess methodological feasibility and the safety and efficacy of donepezil in preventing postoperative delirium after elective total hip replacement surgery in older people without pre‐existing dementia. The hypothesis was that donepezil would reduce the incidence of postoperative delirium. Methods A double blind, placebo controlled, parallel group randomized trial was undertaken. Patients were block randomized pre‐operatively to receive placebo or donepezil 5 mg immediately following surgery and every 24 h thereafter for a further three days. The main outcome was the incidence of delirium (using the Delirium Symptom Interview). The secondary outcome was length of hospital stay. Results Thirty‐three patients (mean age 67 years; 17 males, 16 females) completed the study (19 donepezil, 14 placebo). Donepezil was well tolerated with no serious adverse events. Postoperative delirium occurred in 21.2% of subjects. Donepezil did not significantly reduce the incidence of delirium. The unadjusted risk ratio (donepezil vs placebo) for delirium was 0.29 (95% CI = 0.06,1.30) (χ²_[1] = 3.06; p = 0.08). Mean length of hospital stay was 9.9 days for the donepezil group vs 12.1 days in the placebo group; difference in means = −2.2 days (95% CI = −0.39,4.78) (t_[31] = 1.73: p = 0.09). Conclusions The experimental paradigm was feasible and acceptable. Donepezil did not significantly reduce the incidence of delirium or length of hospital stay, however for both outcomes there was a consistent trend suggesting possible benefit. The sample size required for a definitive trial (99% power, alpha 0.05) would be 95 subjects per arm. Copyright © 2006 John Wiley & Sons, Ltd.