A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement.
OBJECTIVE
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.
Sampson
Elizabeth L
EL
Metabolic and Clinical Trials Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, London, UK. e.sampson@medsch.ucl.ac.uk
Raven
Peter R
PR
Ndhlovu
Patricia N
PN
Vallance
Aaron
A
Garlick
Nicholas
N
Watts
Julie
J
Blanchard
Martin R
MR
Bruce
Angela
A
Blizard
Robert
R
Ritchie
Craig W
CW
D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip; D003693:Delirium / Q000175:diagnosis / Q000188:drug therapy*; D000077265:Donepezil; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D004739:England; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D015994:Incidence; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil