title: A randomized, double-blind, placebo-controlled trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative delirium after elective total hip replacement.
abstract: 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.
authors.affiliation: Metabolic and Clinical Trials Unit, Department of Mental Health Sciences, Royal Free & University College Medical School, London, UK. e.sampson@medsch.ucl.ac.uk
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Sampson
authors.forename: Peter R
authors.initials: PR
authors.lastname: Raven
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Ndhlovu
authors.forename: Aaron
authors.initials: A
authors.lastname: Vallance
authors.forename: Nicholas
authors.initials: N
authors.lastname: Garlick
authors.forename: Julie
authors.initials: J
authors.lastname: Watts
authors.forename: Martin R
authors.initials: MR
authors.lastname: Blanchard
authors.forename: Angela
authors.initials: A
authors.lastname: Bruce
authors.forename: Robert
authors.initials: R
authors.lastname: Blizard
authors.forename: Craig W
authors.initials: CW
authors.lastname: Ritchie
mesh_terms: 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
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil