title: Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture.
abstract: OBJECTIVE
  To determine whether donepezil hydrochloride can reduce the prevalence and severity of delirium in older adults undergoing hip fracture repair.
  
  
  METHODS
  Pilot double-masked randomized placebo-controlled trial.
  
  
  METHODS
  Large academic medical center.
  
  
  METHODS
  Sixteen individuals aged 70 and older with hip fracture.
  
  
  METHODS
  Donepezil 5 mg or placebo was randomly allocated and initiated within 24 hours of surgery, preoperatively or postoperatively. Daily treatment was continued for 30 days or until side effects or the clinical situation required termination.
  
  
  METHODS
  All outcomes were ascertained masked to treatment status. Information on drug tolerability and safety was obtained from the participant, nurse, and medical record. Delirium presence and severity were measured during daily hospital interviews and at 2, 4, and 6 weeks after surgery after a standardized assessment using the Confusion Assessment Method (CAM) and the Memorial Delirium Assessment Scale (MDAS).
  
  
  RESULTS
  Participants in the donepezil and placebo arms had similar baseline characteristics. Participants in the donepezil arm experienced significantly more side effects. In longitudinal models, there were no significant differences between the donepezil and placebo arms with regard to delirium presence over time (odds ratio = 0.9, 95% confidence interval (CI) = 0.4-2.3) or delirium severity over time (effect size = -0.2 on 30-point MDAS scale, 95%CI = -1.5-1.2).
  
  
  CONCLUSIONS
  Participants randomized to donepezil had no significant improvement in delirium presence or severity but experienced more side effects. Overall, sufficient evidence was not found from this pilot study to warrant a definitive Phase III trial.
authors.affiliation: Division of General Medicine and Primary Care, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. emarcant@bidmc.harvard.edu
authors.forename: Edward R
authors.initials: ER
authors.lastname: Marcantonio
authors.forename: Kerry
authors.initials: K
authors.lastname: Palihnich
authors.forename: Paul
authors.initials: P
authors.lastname: Appleton
authors.forename: Roger B
authors.initials: RB
authors.lastname: Davis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003693:Delirium / Q000188:drug therapy*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006620:Hip Fractures / Q000601:surgery*; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D010865:Pilot Projects; D010880:Piperidines / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
references.citation: N Engl J Med. 2004 Jul 1;351(1):56-67
references.pmid: 15229308
references.citation: Cochrane Database Syst Rev. 2008 Jan 23;(1):CD005317
references.pmid: 18254077
references.citation: J Geriatr Psychiatry Neurol. 1992 Jan-Mar;5(1):14-21
references.pmid: 1571069
references.citation: JAMA. 1963 Sep 21;185:914-9
references.pmid: 14044222
references.citation: Lancet. 1981 Sep 26;2(8248):651-3
references.pmid: 6116042
references.citation: N Engl J Med. 1999 Mar 4;340(9):669-76
references.pmid: 10053175
references.citation: Am J Psychiatry. 1996 Feb;153(2):231-7
references.pmid: 8561204
references.citation: J Am Geriatr Soc. 1988 Jun;36(6):525-30
references.pmid: 2897391
references.citation: J Gerontol A Biol Sci Med Sci. 2006 Feb;61(2):204-8
references.pmid: 16510867
references.citation: Lancet. 2010 Nov 27;376(9755):1829-37
references.pmid: 21056464
references.citation: Ann Intern Med. 1990 Dec 15;113(12):941-8
references.pmid: 2240918
references.citation: J Am Geriatr Soc. 2005 Oct;53(10):1658-66
references.pmid: 16181163
references.citation: J Pain Symptom Manage. 1997 Mar;13(3):128-37
references.pmid: 9114631
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: J Gerontol A Biol Sci Med Sci. 2008 Jul;63(7):764-72
references.pmid: 18693233
references.citation: Psychol Med. 1994 Feb;24(1):145-53
references.pmid: 8208879
references.citation: J Am Geriatr Soc. 2000 Jun;48(6):618-24
references.pmid: 10855596
references.citation: Int J Geriatr Psychiatry. 2007 Apr;22(4):343-9
references.pmid: 17006875
references.citation: Am J Geriatr Psychiatry. 2005 Dec;13(12):1100-6
references.pmid: 16319303
references.citation: J Am Geriatr Soc. 2001 May;49(5):516-22
references.pmid: 11380742
references.citation: Osteoporos Int. 2004 Nov;15(11):897-902
references.pmid: 15490120
references.citation: N Engl J Med. 2006 Mar 16;354(11):1157-65
references.pmid: 16540616
references.citation: J Am Med Dir Assoc. 2006 Sep;7(7):412-5
references.pmid: 16979083
references.citation: Ann Intern Med. 2010 Jun 1;152(11):726-32
references.pmid: 20335313
references.citation: Am J Geriatr Psychiatry. 1998 Winter;6(1):31-41
references.pmid: 9469212