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

Int J Geriatr Psychiatry. 2007 Apr;22(4):343-9. doi: 10.1002/gps.1679.


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) (chi(2) ([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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arthroplasty, Replacement, Hip*
  • Delirium / diagnosis
  • Delirium / drug therapy*
  • Donepezil
  • Double-Blind Method
  • Elective Surgical Procedures
  • England
  • Female
  • Hospitals, Teaching
  • Humans
  • Incidence
  • Indans / adverse effects
  • Indans / therapeutic use*
  • Length of Stay
  • Male
  • Mental Status Schedule
  • Middle Aged
  • Nootropic Agents / adverse effects
  • Nootropic Agents / therapeutic use*
  • Odds Ratio
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / drug therapy*
  • Treatment Outcome


  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil