Name:	Donepezil
Other Names:	Aricept™
Therapeutic Applications:	cognition/memory enhancement
Therapy Types:	pharmacological
Mechanisms:	cholinesterase inhibitors
Development Status:	approved in U.S.
FDA Phase:	FDA approved
Role in Alzheimer's Disease:	Improves cognition, global function, and activities of daily living.
Pharmacological Role:	Inhibits the breakdown of acetylcholine, a neurotransmitter important to cognitive function.
Contraindications:	Donepezil is contraindicated in patients with known hypersensitivity to the drug or to other piperidine derivatives. Should be prescribed with caution to patients with sick-sinus syndrome or other cardiac conduction abnormalities, asthma, seizures, active gastrointestinal disease, or in patients receiving non-steroidal antiinflammatory agents.
Side Effects:	Diarrhea, vomiting, nausea, fatigue, insomnia, and anorexia, but in most cases, such side effects are mild and decline with continued use of the drug. Overall, a good side effects profile, without hepatotoxicity and with less nausea than tacrine.
Evidence pro its efficacy:	Several clinical trials studies have shown Donepezil to be well tolerated and improved cognition and global function in patients with mild to moderately severe Alzheimer's disease (AD).
Evidence con its efficacy:	It doesn't work terrifically (probably a third of the patients respond), and may not work at all in advanced cases of AD. It doesn't appear to influence the underlying progression of the disease.
Dosage:	Donepezil is available in 5- and 10-mg tablets; it is administered once daily at bedtime. Treatment should commence with the 5-mg dose; after 4 to 6 weeks, the dosage can be increased to 10 mg if the patient does not respond adequately to the lower dosage.
Companies:	Eisai Incoporated, Pfizer, Inc.
Notes:	Donepezil is being studied for use vascular dementia, which frequently develops following a stroke. Several placebo-controlled trials have found it improves cognitive function in people with vascular dementia. link to Aricept Web Site. See also ARF news story. See Medline Plus Drug Information: Donepezil [MedMaster] and Donepezil (Systemic) [USP DI].

References

Black S, Roman GC, Geldmacher DS, Salloway S, Hecker J, Burns A, Perdomo C, Kumar D, Pratt R. Efficacy and Tolerability of Donepezil in Vascular Dementia. Positive Results of a 24-Week, Multicenter, International, Randomized, Placebo-Controlled Clinical Trial. Stroke. 2003 Sep 11. Abstract

Wilkinson D, Doody R, Helme R, Taubman K, Mintzer J, Kertesz A, Pratt RD. Donepezil in vascular dementia: A randomized, placebo-controlled study. Neurology. 2003 Aug 26;61(4):479-86. Abstract

Pratt RD. Patient populations in clinical trials of the efficacy and tolerability of donepezil in patients with vascular dementia. J Neurol Sci. 2002 Nov 15;203-204:57-65. Abstract

Winblad B, Engedal K, Soininen H, Verhey F, Waldemar G, Wimo A, Wetterholm AL, Zhang R, Haglund A, Subbiah P; Donepezil Nordic Study Group. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 2001 Aug 14;57(3):489-95. Abstract

Kosasa T, Kuriya Y, Matsui K, Yamanishi Y. Inhibitory effect of orally administered donepezil hydrochloride (E2020), a novel treatment for Alzheimer's disease, on cholinesterase activity in rats. Eur J Pharmacol. 2000 Feb 18;389(2-3):173-9. Abstract

Staff RT, Gemmell HG, Shanks MF, Murray AD, Venneri A. Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy. Nucl Med Commun. 2000 Jan;21(1):37-41. Abstract

Evans M, Ellis A, Watson D, Chowdhury T. Sustained cognitive improvement following treatment of Alzheimer's disease with donepezil. Int J Geriatr Psychiatry. 2000 Jan;15(1):50-3. Abstract

Greenberg SM, Tennis MK, Brown LB, Gomez-Isla T, Hayden DL, Schoenfeld DA, Walsh KL, Corwin C, Daffner KR, Friedman P, Meadows ME, Sperling RA, Growdon JH. Donepezil therapy in clinical practice: a randomized crossover study. Arch Neurol. 2000 Jan;57(1):94-9. Abstract

Robert PH, Gokalsing E, Bertogliati C. [Cholinergic hypothesis and Alzheimer's disease: the place of donepezil]. Encephale. 1999 Nov;25 Spec No 5:23-7; discussion 28-9.

Burns A, Rossor M, Hecker J, Gauthier S, Petit H, Moller HJ, Rogers SL, Friedhoff LT. The effects of donepezil in Alzheimer's disease - results from a multinational trial. Dement Geriatr Cogn Disord. 1999 May-Jun;10(3):237-44. Abstract

Kryger G, Silman I, Sussman JL. Protein, Structure Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti- Alzheimer drugs. Structure Fold Des. 1999 Mar 15;7(3):297- 307. Abstract

Doody RS. Clinical profile of donepezil in the treatment of Alzheimer's disease. Gerontology. 1999 ;45 Suppl 1():23- 32. Abstract

Warner JP. Evidence-based psychopharmacology 1. Appraising a single therapeutic trial: what is the evidence for treating early Alzheimer's disease with donepezil? J Psychopharmacol (Oxf). 1999;13(3):308-12. Abstract

Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT. A 24- week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group. Neurology. 1998 Jan;50(1):136-45. Abstract

Rogers SL. Perspectives in the management of Alzheimer's disease: clinical profile of donepezil. Dement Geriatr Cogn Disord. 1998;9 Suppl 3:29-42. Abstract

Wilkinson D. Clinical experience with Donepezil (Aricept) in the UK. J Neural Transm Suppl. 1998;54:311-5. Abstract