A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement
Article first published online: 27 SEP 2006
Copyright © 2006 John Wiley & Sons, Ltd.
International Journal of Geriatric Psychiatry
Volume 22, Issue 4, pages 343–349, April 2007
How to Cite
Sampson, E. L., Raven, P. R., Ndhlovu, P. N., Vallance, A., Garlick, N., Watts, J., Blanchard, M. R., Bruce, A., Blizard, R. and Ritchie, C. W. (2007), 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. Geriat. Psychiatry, 22: 343–349. doi: 10.1002/gps.1679
- Issue published online: 21 MAR 2007
- Article first published online: 27 SEP 2006
- Manuscript Accepted: 1 AUG 2006
- Manuscript Received: 29 MAR 2006
- Pfizer Esai, UK
- donepezil hydrochloride;
- randomized controlled trial
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.
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.
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 = 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 = 1.73: p = 0.09).
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.