Donepezil in Severe Alzheimer’s disease: A Review of Treatment Considerations with Disease Progression

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Neuendorff, Melanie
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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.
donepezil, Alzheimer's disease