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A systematic review of adverse events in the placebo arm of donepezil trials: the role of cognitive impairment

Published online by Cambridge University Press:  04 January 2012

Martina Amanzio ,
Fabrizio Benedetti  and
Lene Vase
Martina Amanzio*
Affiliation:
Department of Psychology, University of Turin, Turin, Italy Neuroscience Institute of Turin (NIT), Turin, Italy
Fabrizio Benedetti
Affiliation:
Department of Neuroscience, University of Turin Medical School, Turin, Italy National Institute of Neuroscience (INN), Turin, Italy
Lene Vase
Affiliation:
Department of Psychology, Aarhus University, Aarhus, Denmark Danish Pain Research Center, Aarhus University Hospital, Noerrebrogade 44, DK- 8000 Aarhus C, Denmark
*
Correspondence should be addressed to: Dr. Martina Amanzio, Department of Psychology, University of Turin, Via Verdi 10, 10123, Turin, Italy. Phone: +39-11-6702468; Fax: +39-11-6702061. Email: martina.amanzio@unito.it.
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Abstract

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”.

Keywords

Alzheimer's diseasemild cognitive impairmentrandomized controlled trialsnocebo
Type
Review Article
Information
International Psychogeriatrics , Volume 24 , Issue 5 , May 2012 , pp. 698 - 707
Copyright
Copyright © International Psychogeriatric Association 2012

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