Effectiveness of Donepezil Therapy in Advanced Alzheimer’s Disease

Bengt Winblad
European Psychiatric Review, 2009;2(1):53-55
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Abstract

Alzheimer’s disease (AD) is a progressive, degenerative disease. In the advanced stages, cognitive and functional abilities become compromised to the extent that most patients require total, full-time care, usually in specialised nursing homes. Loss of cognition affects functional autonomy, which is gradually lost, and psychiatric and behavioural symptoms often become problematic for both patients and their carers/families. The cholinesterase inhibitor donepezil is licensed for the treatment of mild to moderate AD in many regions worldwide, with the indication expanded to encompass severe AD in eight countries: the US, Canada, Japan, Australia, India, New Zealand, Thailand and the Philippines. Approval for use in severe AD was granted by the US Food and Drug Administration (FDA) in 2006 on the basis of strong evidence from the Swedish Nursing Home Severe AD study. In total, three prospective randomised clinical trials of donepezil in severe AD have now been conducted and a subanalysis of a fourth study has provided additional information. Overall, these studies show that donepezil treatment is associated with functional and cognitive benefits in patients with severe AD, although behavioural benefits were not consistently observed. Donepezil was well tolerated; side effects were transient, mild to moderately severe and generally cholinergic in nature.

Acknowledgements: Additional editorial support was provided by R Daniel of PAREXEL.
Keywords
Alzheimer’s disease (AD), severe, donepezil
Disclosure Bengt Winblad has received honoraria to participate in symposia and advisory board meetings from Pfizer, Eisai, Ortho-McNeill Neurologics, Merz, Lundbeck, Janssen-Cilag and Forest Laboratories. He has received no research grants from nor does he own stocks in these companies. Editorial support was funded by Eisai Inc. and Pfizer Inc.
Received: April 04, 2008 Accepted June 09, 2008
Correspondence: Bengt Winblad, Karolinska University Hospital, Huddinge, 14186 Stockholm, Sweden. E: bengt.winblad@ki.se

About 20% of patients with Alzheimer’s disease (AD) have severe dementia,1 which presents particular challenges. During the more severe stages, cognitive function continues to decline, functional autonomy is lost, psychiatric and behavioural symptoms become increasingly troublesome and patients become less able to communicate and less mobile, eventually leading to a need for complete care.2

The population with severe AD is often considered to be beyond the point at which pharmacological intervention will be beneficial and, indeed, some specialists and treatment guidelines recommend discontinuing treatment in these patients.3 However, a large proportion of patients first presenting to physicians with symptoms of AD are already in the moderate to severe stages of the disease.4 Existing data suggest that patients and their carers benefit if treatment is initiated or is continued in patients with more advanced AD.

Donepezil, a cholinesterase inhibitor (ChEI) widely used for the treatment of AD, was approved by the US Food and Drug Administration (FDA) in 2006 for the treatment of severe AD;5 this represented an extension of the existing licence for the treatment of mild to moderate AD. Licensing in Europe is currently for mild to moderate AD. For patients initiating donepezil treatment during the mild to moderate phase of AD, persistent treatment provides cognitive benefits,6,7 slows functional decline,8 helps behavioural symptoms9 and allows patients to stay at home longer.10 This article will review the clinical evidence for the use of donepezil in patients with more advanced AD.

Guidelines for Treatment of Severe Disease

Treatment guidelines for AD developed in Italy suggest that ChEI therapy should be considered in patients with moderate to severe AD (MSAD) and continued in patients who have derived benefit, even in those with a Mini-Mental State Examination (MMSE) score <10.11 The latest guidelines from the European Federation of Neurological Societies12 advocate the treatment of patients with severe AD (MMSE score <10) with memantine in combination with a ChEI as required. In contrast, UK guidelines from the National Institute of Health and Clinical Excellence (NICE) recommend the use of treatment only in those with moderate disease, continuing treatment while the patient’s MMSE score remains ≥10.3

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