What is the efficacy of Aricept (donepezil) in treating Alzheimer's disease in a typical geriatric patient?

Efficacy of Aricept (Donepezil) in Alzheimer's Disease

Aricept (donepezil) provides modest but consistent improvements in cognition and global function for patients with mild to moderate Alzheimer's disease, though the cognitive benefits do not reach clinically significant thresholds on standard testing scales. 1

Cognitive Outcomes

Donepezil at both 5 mg and 10 mg daily doses produces statistically significant improvements in cognition compared to placebo, but these effects are small. 1 Based on 34 reports from 24 distinct studies, the summary estimates for the ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) show consistent treatment effects, though the average change does not reach the 4-point threshold considered clinically significant. 1

• The cognitive improvements are evident as early as week 3 of treatment and represent approximately a 5-15% benefit over placebo. 1
• Approximately 20-35% of treated patients exhibit a 7-point improvement on neuropsychologic tests, equivalent to delaying one year's decline. 1
• The 10 mg dose shows a dose-response advantage over 5 mg, though the difference is modest. 2

Global Function and Clinical Significance

The most compelling evidence for donepezil's efficacy comes from global assessment measures (CIBIC-plus), which demonstrate clinically significant changes, unlike the ADAS-cog scores. 1 The CIBIC-plus (Clinician's Interview-Based Impression of Change) evaluates four major domains: general function, cognition, behavior, and activities of daily living. 2

• Global function improvements are maintained throughout study durations, typically 24 weeks. 1
• A larger proportion of patients achieve clinically important improvements with donepezil compared to placebo, though statistical significance of these proportions was only reported in select trials. 1

Functional and Behavioral Outcomes

Evidence for functional improvement is less consistent than for cognitive and global outcomes. 1 Donepezil 10 mg/day significantly delayed deterioration in activities of daily living (ADL) by up to 55 weeks in retrospective analyses and improved patients' abilities to perform complex tasks. 1, 3

• Behavioral symptoms and quality of life were not evaluated as extensively or with consistent outcomes across studies. 1
• Donepezil may reduce caregiver burden, though evidence is limited. 3

Duration of Effect and Disease Progression

Short study durations (most ≤6 months) prevent definitive conclusions about donepezil's ability to delay disease progression or its efficacy beyond 6 months. 1 Although differences between treatment and placebo groups were maintained during studies, long-term efficacy data suggest improvements are maintained for approximately 21-81 weeks with 10 mg/day dosing. 3

• For mild cognitive impairment specifically, donepezil reduced conversion rates to Alzheimer's disease in the short term, but differences disappeared by 36 months. 1
• There is no evidence supporting donepezil use in mild cognitive impairment, as putative benefits are minor, short-lived, and associated with significant side effects. 4

Adverse Effects

Adverse events are primarily gastrointestinal (nausea, vomiting, diarrhea) and are dose-related. 1 Withdrawal rates due to adverse events ranged from 0-57% in treatment groups versus 0-20% in placebo groups. 1

• Common side effects include muscle cramps, fatigue, anorexia, and abnormal dreams. 1, 2
• No evidence of hepatotoxicity has been observed, unlike tacrine. 1, 3
• Donepezil 23 mg daily is associated with weight loss. 2

Practical Considerations

The recommended starting dose is 5 mg once daily, which can be increased to 10 mg after 4-6 weeks based on tolerability. 1, 2 The longer titration period (6 weeks versus 7 days) minimizes cholinergic side effects. 3

• Donepezil should be taken with food to reduce gastrointestinal adverse effects. 1
• Some patients may exhibit initial increased agitation that subsides after the first few weeks. 1
• Response assessment should include physician global assessment, caregiver input, and evaluation of cognitive and functional status. 1