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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 delays nursing home placement - Tips from Other Journals
From American Family Physician, 3/15/04 by Caroline Wellbery

Factors that predict nursing home placement in patients with Alzheimer's disease include worsening dementia, behavior disturbances, and caregiver burden. However, most families prefer to keep patients with Alzheimer's disease at home as long as possible. In addition, delaying nursing home placement may reduce overall health care costs. Geldmacher and colleagues studied the role of the cholinesterase inhibitor donepezil in delaying time to nursing home admission.

The study was an observational follow-up to several randomized, placebo-controlled trials investigating the therapeutic benefits of donepezil. At the completion of these trials, patients were invited to continue open-label treatment for up to 240 weeks. Data, including nursing home placement, were recorded, as were the date and reason for placement. Four groups of patients were defined, depending on duration of donepezil use and dosage. These groups included the following: (1) minimal-use patients who received less than the minimum dosage, (2) early moderate-use patients who received adequate dosages but terminated early or did not participate in the open-label extension, (3) delayed-start patients who received adequate dosages only after entering the extension trial, and (4) maximal-use patients who received adequate dosages during the placebo-controlled phase and the extension. The principal outcome was time from entry in a placebo-controlled trial to nursing home placement. Different constructs were analyzed, depending on the duration of successful participation in a clinical trial.

A total of 671 patients with mild to moderate dementia were included in the analyses. Estimated median times to first dementia-related nursing home placement ranged from 44.7 months in the minimal-use group and 66.1 months in the maximal-use group. A delay in first dementia-related nursing home placement of 21.4 months was associated with donepezil use of at least 5 mg daily for at least 36 to 48 weeks. A delay of 17.5 months to permanent nursing home placement was associated with donepezil use of the same dosage and duration. Relative risk ratios (RRs) for nursing home placement in the moderate-use group were not significantly different from those in the minimal-use group but were significantly different from this group in the delayed-start and maximal-use groups. RRs for nursing home placement declined with longer donepezil use across all four groups, a trend that was consistent for the three cohort time constructs analyzed.

According to the results of this study, cumulative sustained exposure to effective doses of donepezil delays time to nursing home placement when placement is for longer than two weeks. Washout periods during the placebo-controlled trials attenuated donepezil's effects, suggesting that treatment of Alzheimer's disease with donepezil should be maintained before important benefits will occur. The authors doubt that selection bias influenced these results, given the similarity of patient characteristics and a follow-up period of up to eight years. Donepezil appears to benefit both cognitive function and behavioral symptoms.

Geldmacher DS, et al. Donepezil is associated with delayed nursing home placement in patients with Alzheimer's disease. J Am Geriatr Soc July 2003;51:937-44.

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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