Donepezil in Severe Alzheimer’s disease: A Review of Treatment Considerations with Disease Progression
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Date
2015-04
Authors
Neuendorff, Melanie
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Abstract
Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects
35 million people worldwide, with the prevalence expecting to double by 2030. Patients with
severe AD (Mini-Mental State Examination (MMSE) score <10) require extensive help with
daily activities, show severe memory impairment, and exhibit major personality and behavioral
changes. Donepezil is one of only two drugs currently approved by the US Food and Drug
Administration (FDA) and Health Canada for use in severe AD. The drug is currently available
in 5mg, 10mg, and a controversial more recently FDA approved 23mg daily dose. This review
will provide a brief background on AD, and discuss the risks, benefits, and current
recommendations for donepezil use in severe disease, with an emphasis on Canadian and US
practices.
Methods: Randomized Controlled Trials (RCTs) concerning the efficacy and safety of
various doses of donepezil (Aricept) use in severe AD were identified using PubMed. Three
original double blind, parallel-group, placebo-controlled, randomized studies, one post-hoc
analysis, and one sub-group analysis were selected for review.
Results: Donepezil benefits
patients with severe AD in areas of cognition and global function. Increased benefits of treatment
correlated with escalading dose in patients with more advanced baseline disease, as measured by
Severe Impairment Battery (SIB) scores. However, more patients assigned to donepezil
discontinued their treatment due to an adverse event (AE) than placebo, and AEs occurred more
frequently and with increasing severity as dose increased.
Conclusion: Donepezil treatment
shows small but measurable benefits in severe AD. Clinicians must weigh these benefits against
the possible AEs when determining the appropriate course of therapy, as recommendations for
discontinuation of cholinesterase inhibitors in advanced AD remain unclear.
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Keywords
donepezil, Alzheimer's disease