Donepezil Discontinuation: Abrupt vs. Tapering
Donepezil can be discontinued abruptly without tapering, as the beneficial effects of donepezil abate over 6 weeks following discontinuation without evidence of a rebound effect. 1
Evidence for Abrupt Discontinuation
The FDA drug label for donepezil specifically addresses discontinuation, stating that:
- Following 6 weeks of placebo washout, the beneficial effects of donepezil abate without evidence of a rebound effect 1
- Clinical trials have successfully used abrupt discontinuation protocols with 3-week and 6-week washout periods 1
This is the highest quality evidence available, coming directly from the FDA-approved drug labeling, which is based on the original clinical trials for donepezil.
Potential Concerns with Abrupt Discontinuation
While the FDA label supports abrupt discontinuation, some research suggests caution:
- A small open-label study in patients with Dementia with Lewy Bodies and Parkinson's Disease with Dementia found that sudden withdrawal of donepezil produced acute cognitive and behavioral decline 2
- This decline was reversed when donepezil was restarted, suggesting that the deterioration was related to the loss of therapeutic effect rather than a withdrawal syndrome 2
Tapering Approach (If Preferred)
If tapering is preferred due to individual patient factors, the following approach can be considered, based on medication tapering guidelines:
- Reduce the dose by 5-10% every 1-2 weeks 3
- For patients on 10mg daily, consider:
- Reducing to 5mg daily for 2-4 weeks
- Then discontinuing completely
Monitoring During Discontinuation
Regardless of whether donepezil is discontinued abruptly or tapered:
- Monitor for cognitive decline, which would represent loss of therapeutic effect rather than withdrawal 1, 2
- Be prepared to restart the medication if significant cognitive or behavioral deterioration occurs 2
- Schedule follow-up within 4-6 weeks of discontinuation to assess cognitive status
Clinical Context
The decision to discontinue donepezil should be based on:
- Lack of therapeutic benefit
- Intolerable side effects
- Patient/family preference
- Advanced disease stage where benefits no longer outweigh risks
Summary
Based on the highest quality evidence (FDA drug labeling), donepezil can be discontinued abruptly without a formal tapering schedule. The beneficial effects will gradually diminish over approximately 6 weeks following discontinuation, without evidence of withdrawal symptoms or rebound effects. If there are specific concerns about individual patient factors, a gradual tapering approach can be considered, but is not required based on the available evidence.