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Donepezil

Donepezil, marketed under the trade name AriceptĀ® (Eisai), is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. It is well absorbed in the gut with an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks. more...

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The clinical utility of donepezil is controversial. Presently, there is no proof that use of donepezil or other similar agents alters the course or progression of Alzheimer's disease. However, controlled studies have shown modest benefits in cognition and behavior with this and similar agents. Therefore, many neurologists, psychiatrists, and primary care physicians use donepezil in patients with Alzheimer's disease. As of the 22 March 2005, the UK National Institute for Clinical Excellence (NICE) withdrew its recommendation for use of the drug for mild-to-moderate AD, on the basis that there is no significant improvement in functional outcome; of quality of life or of behavioral symptoms. However, these data conflict with those of other reports, as is often the case in medicine.

Donepezil is sometimes used in combination with Memantine, a new agent for Alzheimer's disease which is in the same chemical class. The response to both together is superior to either alone.

Donepezil has been tested in other disorders which cause dementia including Lewy body dementia and Vascular dementia, but it is not currently approved for these indications.

Sources

  • Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
  • Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4

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Donepezil may improve mild cognitive impairment
From AORN Journal, 9/1/04

People with mild cognitive impairment taking the medication donepezil were at reduced risk of progressing to Alzheimer's disease during the first 18 months of a three-year study when compared with their counterparts who were taking a placebo, according to a July 18, 2004, news release from the National Institutes of Health. The reduced risk of progressing from mild cognitive impairment to a diagnosis of Alzheimer's disease among participants on donepezil no longer existed after 18 months, and by the end of the study, the probability of progressing to Alzheimer's disease was the same in the two groups.

The study compared donepezil, vitamin E, and placebo in participants with mild cognitive impairment to see whether the medications would delay or prevent progression to Alzheimer's disease. During the course of the study, among people who did progress to Alzheimer's disease, the participants taking donepezil averaged 661 days until a diagnosis of Alzheimer's disease; a second group taking vitamin E averaged 540 days from mild cognitive impairment to Alzheimer's disease; and those taking placebo averaged 484 days to Alzheimer's disease. The investigators reported a statistically significant effect when donepezil was compared to placebo but said there was no apparent benefit from vitamin E.

The National Institute on Aging and the scientists conducting the study emphasized that further analyses are needed to assess the practical, clinical implications of the new data. The study is complex, and the effects appear to be time limited.

People with mild cognitive impairment have notable memory Loss and are at higher risk for developing Alzheimer's disease than those of similar age and health in the general population. Donepezil was used in the study because of its current approval as a medication for treating patients already diagnosed with Alzheimer's disease. The antioxidant vitamin E has been linked in animal research to a reduction in cognitive decline and in some population studies to reduced risk of Alzheimer's disease.

In addition to being tested for Alzheimer's disease, study participants were assessed in specific areas of cognitive function, including orientation, Language, and attention, and in everyday function (ie, activities of daily living). These secondary analyses suggest that decline among the group taking donepezil occurred at a slower rate on tests of global cognition, memory, and language than among the other participants during the first half of the study but progressed at the same rate thereafter.

The Memory Impairment Study was conducted nationwide at 69 sites. It involved 769 participants with mild cognitive impairment, who were followed for three years and tested for Alzheimer's disease at six-month intervals during their 36 months in the study. The average age of the participants was 73 years.

Donepezil May Have Short-Term Benefit for Mild Cognitive Impairment; More Analyses Needed to Assess Clinical Implications of New Data (news release, Bethesda, Md: National Institutes of Health, July 18, 2004) http://www.nih.gov/news/pr/jul2004/nia-18.htm (accessed 3 Aug 2004).

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COPYRIGHT 2004 Gale Group

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