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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 in the treatment of vascular dementia
From American Family Physician, 11/1/04 by Mark H. Ebell

Clinical Question

Is donepezil effective in the treatment of vascular dementia?

Evidence-Based Answer

Donepezil in a dosage of 10 mg daily provides a small benefit in patients with mild to moderate vascular dementia and generally is well tolerated.

Practice Pointers

Donepezil, a cholinesterase inhibitor, is somewhat effective in the treatment of mild to moderate cognitive impairment caused by Alzheimer's disease. Malouf and Birks examined the evidence from two similar manufacturer-sponsored studies of donepezil in a total of 1,219 patients with vascular cognitive impairment (sometimes called "multi-infarct dementia" or "vascular dementia"). Both studies were randomized, double blinded, and placebo controlled.

Validated diagnostic criteria were used to identify patients with probable vascular dementia. Given the challenge of diagnosing dementia subtypes before death, however, a substantial number of patients probably had mixed vascular and Alzheimer's dementia. (1)

Patients who took donepezil performed slightly better on tests of cognitive function, such as the Mini-Mental State Examination (weighted mean difference, 1.2 points at 24 weeks on this 30-point scale) and the Alzheimer's Disease Assessment Scale cognitive subscale. Patients who took the 10-mg dosage did better than those who took the 5-mg dosage. Patients who took the 10-mg dosage (but not the 5-mg dosage) also did better than control patients on the Clinical Dementia Rating scale. There was no difference between groups on the Alzheimer's Disease Functional Assessment and Change Scale, which focuses on activities of daily living. Compared with the lower dosage and placebo, the 10-mg dosage was associated with more adverse events (odds ratio for at least one adverse event, 1.95; 95 percent confidence interval, 1.20 to 3.15; P = .007). Most adverse events were minor, and the pooled dropout rate and the rate of severe adverse events were similar between groups.

REFERENCE

(1.) Hogervorst E, Bandelow S, Combrinck M, Irani S, Smith AD. The validity and reliability of 6 sets of clinical criteria to classify Alzheimer's disease and vascular dementia in cases confirmed post-mortem: added value of a decision tree approach. Dement Geriatr Cogn Disord 2003;16:170-80.

MARK H. EBELL, M.D., M.S. Malouf R, Birks J. Donepezil for vascular cognitive impairment. Cochrane Database Syst Rev 2004;(3):CD004395.

COPYRIGHT 2004 American Academy of Family Physicians
COPYRIGHT 2004 Gale Group

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