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Clinical question
Are cholinesterase inhibitors effective in patients with Alzheimer's
disease?
Bottom line
The evidence supporting the effectiveness of cholinesterase inhibitors is
based on exceedingly small effects found in poorly analyzed studies. Studies
of Alzheimer's drugs need to be carefully scrutinized for methodologic
errors that inflate the appearance of benefit.
Reference
Kaduszkiewicz H, Zimmermann T, Beck-Bornholdt HP, van den Bussche H.
Cholinesterase inhibitors for patients with Alzheimer's disease: systematic
review of randomised trials. BMJ 2005; 331:321-27.
Study design: Meta-analysis (randomized controlled trials)
Setting: Various (meta-analysis)
Synopsis
Three treatments for Alzheimer's disease work by inhibiting cholinesterase:
donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). The
authors of this meta-analysis combined the results of 22 randomized
controlled trials evaluating the drugs' effects on clinical outcomes. The
research was identified by searching 3 databases for research in any
language. Three researchers independently selected studies on the basis of
predetermined criteria. The quality of the studies was poor for many of
these studies; the most common problem was that the results were not
analyzed by intention to treat, the lack of which tends to inflate evidence
of benefit. Most studies used the standard evaluation tool, the Alzheimer's
Disease Assessment Scale--cognitive subscale, which uses scores ranging from
0 (no impairment) to 70 (very severe impairment). For all 3 drugs, the
differences between the treatment groups and placebo groups was a minimal
1.5 points to 3.9 points. In 12 trials, effectiveness was also measured
using the Clinician's Interview Base on Impression of Change; these scores
were not significantly different between treatment and placebo groups. One
study that used a measure of cognitive decline showed an average 5 months
delay with donepezil compared with placebo before a clinically evident
functional decline was seen.
Technorati Tags: Alzheimer's-disease, donepezil, Aricept, rivastigmine, Exelon, galantamine, Razadyne
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