Higher-dose (23 mg/day) donepezil formulation for the treatment of patients with moderate-to-severe Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the elderly. An estimated 5.4 million people in the United States have AD, and its prevalence is expected to increase rapidly in the coming years. Few US Food and Drug Administration (FDA)-approved treatment options for AD are currently available. Donepezil is 1 of only 2 therapies approved in the United States for the treatment of moderate-to-severe AD. In 2010, the FDA approved a higher daily dose of donepezil (23 mg/day) for the treatment of AD in the moderate-to-severe stages based on positive results from a large, global, phase 3 clinical trial that compared switching to donepezil 23 mg/day with continuing treatment with donepezil 10 mg/day. In that trial, no benefit was seen in the co-primary endpoint of global functioning; however, donepezil 23 mg/day provided a small but significant improvement in the cognitive endpoint compared with donepezil 10 mg/day. A subgroup analysis subsequently showed that the cognitive benefits were significant irrespective of concomitant memantine use. Adverse events were mainly gastrointestinal related and were more prevalent in patients receiving the donepezil 23-mg/day dose during the first month of therapy, but were relatively infrequent thereafter. These data indicate that once-daily donepezil 23 mg may be an effective treatment option for patients with moderate-to-severe AD with or without concomitant memantine. This article reviews the rationale for using higher-dose donepezil, the clinical data supporting its use, and some of the practical implications that should be considered by practicing physicians when using donepezil 23 mg/day for patients with AD.