Can donepezil (Aricept) accelerate dementia progression?

Donepezil Does Not Accelerate Dementia Progression

Donepezil does not accelerate dementia progression; rather, it provides modest benefits in cognitive function, activities of daily living, and global clinical state for patients with mild to moderate Alzheimer's disease. 1, 2

Mechanism and Benefits of Donepezil

Donepezil is a reversible inhibitor of acetylcholinesterase that works by:

• Enhancing cholinergic function by increasing acetylcholine concentration through inhibition of its breakdown 3
• Providing modest but statistically significant improvements in cognitive function 2
• Demonstrating benefits in global clinical function and activities of daily living 2

The American College of Physicians and American Geriatrics Society recommend donepezil as a first-line pharmacological treatment for mild to moderate Alzheimer's disease due to its once-daily dosing, favorable side effect profile, and demonstrated efficacy 1.

Evidence of Efficacy

Multiple studies have demonstrated that donepezil provides benefits rather than accelerating progression:

• Cochrane review evidence shows donepezil improves cognitive function measured by ADAS-Cog (mean difference -2.67 points) and MMSE (mean difference 1.05 points) compared to placebo after 26 weeks of treatment 2
• Donepezil also improves activities of daily living and clinician-rated global impression of change 2
• These benefits have been observed across the spectrum of mild, moderate, and severe Alzheimer's disease 4

Dosing and Duration Considerations

• Standard dosing begins with 5 mg once daily, increasing to 10 mg once daily after 4-6 weeks if tolerated 1, 5
• For moderate to severe Alzheimer's disease, 10 mg daily is recommended, with the option to add memantine for add-on therapy 1
• Treatment should be continued for at least 6-12 months before assessing efficacy 1
• Beneficial response can be determined through physician's global assessment, caregiver report, neuropsychological assessment, or evidence of behavioral/functional changes 5

Side Effects and Management

The most common adverse effects include:

• Gastrointestinal symptoms: nausea, vomiting, diarrhea 5, 1
• Initial increase in agitation that typically subsides after a few weeks 5

Management strategies include:

• Starting with lower doses and gradual titration
• Taking medication with food
• Considering switching to another cholinesterase inhibitor if side effects are intolerable 1

When to Discontinue

Consider discontinuation if:

• Side effects develop and do not resolve
• Adherence is poor
• Deterioration continues at the pretreatment rate after 6-12 months of treatment 5
• Development of severe or end-stage dementia 1

Important Considerations

1. Assessment period: Observation for 6-12 months is usually necessary to assess potential benefit 5

2. Individual response: Patients who do not respond to one cholinesterase inhibitor may respond to another 5

3. Monitoring: Regular reassessment should look for stabilization or slowing of cognitive decline, improvement or stabilization in functional abilities, changes in behavior, and caregiver reports 1

4. Special populations: Lower weight individuals (<55 kg) may experience more side effects including nausea, vomiting, and weight loss 3

In conclusion, the evidence strongly supports that donepezil does not accelerate dementia progression but rather provides modest benefits across multiple domains of function for patients with Alzheimer's disease. The decision to use donepezil should be based on a careful consideration of its potential benefits against possible side effects for each individual patient.