Can donepezil (Aricept) be discontinued immediately in a patient with dementia and elevated liver enzymes?

Can Donepezil Be Discontinued Immediately?

Donepezil can be safely tapered to discontinuation, especially in advanced dementia where there is perceived lack of benefit or when adverse effects outweigh benefits. 1

Evidence for Safe Discontinuation

The Mayo Clinic guidelines explicitly state that cholinesterase inhibitors like donepezil are "safe to taper to off, especially when there is perceived lack of benefit." 1 This is particularly relevant in your patient with elevated liver enzymes, as the medication may be contributing to hepatic stress without providing meaningful clinical benefit.

Key Considerations Supporting Discontinuation

In the context of elevated liver enzymes, discontinuation is particularly appropriate because:

• Donepezil lacks long-term benefit, particularly in advanced dementia 1
• The medication is indicated only for mild to moderate dementia, not severe disease 1
• Common adverse effects include nausea, vomiting, diarrhea, nightmares, and bradyarrhythmias 1
• While donepezil itself does not typically cause hepatotoxicity 2, the presence of elevated liver enzymes warrants medication review and potential discontinuation of non-essential drugs

Discontinuation Method

The recommended approach is gradual tapering rather than abrupt cessation. 1 While the guidelines indicate it is "safe to taper to off," they do not specify immediate discontinuation. The rationale for tapering includes:

• Avoiding potential rebound worsening of cognitive or behavioral symptoms 3
• Minimizing withdrawal-related adverse effects
• Allowing time to monitor for any clinical deterioration

Practical Tapering Approach

A reasonable tapering schedule would be:

• If on 10 mg daily, reduce to 5 mg daily for 2-4 weeks, then discontinue 1
• If on 5 mg daily, can discontinue after 1-2 weeks of observation
• Monitor for increased agitation during the first few weeks, which may occur but typically subsides 3

Clinical Context for This Decision

The evidence shows that donepezil provides only modest, statistically significant but not clinically important benefits:

• Average improvement on ADAS-Cog scale was -2.02 to -2.92 points (threshold for clinical significance is ≥4 points) 1
• While some patients show clinically important individual responses, most studies did not demonstrate statistical significance for this subset 1
• Benefits are maintained for only 21-81 weeks before gradual deterioration resumes 2

When Discontinuation is Most Appropriate

Discontinue donepezil when: 1

• Disease has progressed to severe/advanced dementia
• Patient experiences adverse effects (nausea, vomiting, diarrhea, bradycardia)
• There is no perceived clinical benefit
• Elevated liver enzymes or other medical complications require medication burden reduction
• Patient or family wishes to simplify medication regimen

Important Caveats

Do not confuse lack of dramatic improvement with lack of benefit. 4 Some patients may be experiencing slowed decline rather than improvement, which becomes apparent only after discontinuation. However, in advanced dementia, this consideration becomes less relevant as the medication is not indicated for severe disease. 1

Monitor for: 3

• Acute worsening of cognition or behavior in the 4-6 weeks following discontinuation
• Increased agitation or neuropsychiatric symptoms
• Changes in functional status

If significant deterioration occurs after discontinuation, reinitiation can be considered, though this is rarely necessary in advanced dementia. 1