PMID- 22217339
OWN - NLM
STAT- MEDLINE
DCOM- 20120816
LR  - 20181201
IS  - 1741-203X (Electronic)
IS  - 1041-6102 (Linking)
VI  - 24
IP  - 5
DP  - 2012 May
TI  - A systematic review of adverse events in the placebo arm of donepezil trials: the 
      role of cognitive impairment.
PG  - 698-707
LID - 10.1017/S1041610211002420 [doi]
AB  - BACKGROUND: In randomized clinical trials, adverse events (AEs) are reported for 
      the drug under evaluation and compared with the placebo group. Patients who 
      receive placebo treatment report a high frequency of AEs, but little is 
      understood about the nature of these. No study has yet analyzed the level of 
      cognitive impairment as a crucial aspect for the AEs reported by patients. 
      METHODS: The rates of AEs reported by patients with mild cognitive impairment 
      (MCI) and Alzheimer's disease (AD) in the placebo arms of donepezil trials were 
      compared using a systematic review approach. PubMed was searched with the terms 
      "MCI and donepezil" as well as "AD and donepezil" from January 1989 to December 
      2010. Nineteen studies fulfilled the selection criteria (3 MCI, n = 783; 16 AD, n 
      = 2,059). RESULTS: An overall comparison of 81 categories of AEs in the placebo 
      arm of MCI versus AD trials showed that patients in AD trials experienced a 
      significantly higher number of AEs than patients in MCI trials (p < 0.001). 
      CONCLUSIONS: This is the first study showing that AD patients may be at a greater 
      risk of developing AEs than MCI patients. This may be related to a greater 
      presence of somatic comorbidity predisposing them to express emotional distress 
      as physical symptoms and/or to AD patients being frailer and therefore more 
      susceptible to AEs. The phenomena we observed may be interpreted in terms of the 
      "nocebo effect".
FAU - Amanzio, Martina
AU  - Amanzio M
AD  - Department of Psychology, University of Turin, Turin, Italy. 
      martina.amanzio@unito.it
FAU - Benedetti, Fabrizio
AU  - Benedetti F
FAU - Vase, Lene
AU  - Vase L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PT  - Systematic Review
DEP - 20120104
PL  - England
TA  - Int Psychogeriatr
JT  - International psychogeriatrics
JID - 9007918
RN  - 0 (Indans)
RN  - 0 (Nootropic Agents)
RN  - 0 (Piperidines)
RN  - 0 (Placebos)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Aged
MH  - Alzheimer Disease/*drug therapy/psychology
MH  - Cognitive Dysfunction/*chemically induced/etiology
MH  - Donepezil
MH  - Humans
MH  - Indans/adverse effects/*therapeutic use
MH  - Nootropic Agents/adverse effects/*therapeutic use
MH  - Piperidines/adverse effects/*therapeutic use
MH  - Placebos/*adverse effects
MH  - Randomized Controlled Trials as Topic
EDAT- 2012/01/06 06:00
MHDA- 2012/08/17 06:00
CRDT- 2012/01/06 06:00
PHST- 2012/01/06 06:00 [entrez]
PHST- 2012/01/06 06:00 [pubmed]
PHST- 2012/08/17 06:00 [medline]
AID - S1041610211002420 [pii]
AID - 10.1017/S1041610211002420 [doi]
PST - ppublish
SO  - Int Psychogeriatr. 2012 May;24(5):698-707. doi: 10.1017/S1041610211002420. Epub 
      2012 Jan 4.