What to do about agitation in a patient after stopping donepezil (Aricept)?

Managing Agitation After Stopping Donepezil

For patients experiencing agitation after stopping donepezil, the agitation is likely a withdrawal effect that typically resolves within a few weeks; monitoring and supportive care are recommended while the symptoms subside.

Understanding Donepezil Withdrawal and Agitation

• Donepezil can cause an initial increase in agitation when started, which typically subsides after the first few weeks of therapy 1, 2
• Similarly, abrupt discontinuation of donepezil can lead to withdrawal symptoms including worsening of dementia symptoms and agitation, potentially culminating in delirium 3
• Withdrawal effects after stopping cholinesterase inhibitors like donepezil are related to the sudden decrease in acetylcholine levels in the brain 3

Management Approach for Post-Discontinuation Agitation

Step 1: Assess Severity and Impact

• Determine if the agitation is severe enough to cause distress or pose safety concerns 1
• Evaluate for other potential causes of agitation (pain, infection, other medication effects) 1

Step 2: Consider Medication Options

• If agitation is severe and causing significant distress:
  • Consider restarting donepezil at a lower dose (5 mg daily) if there were no serious adverse effects that prompted discontinuation 1, 3
  • Administer donepezil in the morning rather than at bedtime to minimize sleep disturbances 4

Step 3: Non-Pharmacological Interventions

• Implement behavioral interventions and environmental modifications 1
• Provide reassurance and maintain a calm, structured environment 1
• Avoid physical restraints which may worsen agitation 1

Step 4: Monitor and Reassess

• Observe for gradual resolution of agitation, which typically occurs over a 1-2 week period 2, 3
• If agitation persists beyond 2 weeks, reassess for other potential causes 1

Important Considerations

• Donepezil itself is not effective for treating agitation in Alzheimer's disease, as demonstrated in a 12-week randomized controlled trial 5
• If donepezil was discontinued due to lack of benefit after an adequate trial (6-12 months), restarting may not be beneficial 1
• If donepezil was discontinued due to side effects, consider switching to another cholinesterase inhibitor (rivastigmine or galantamine) as patients who don't respond to one may respond to another 1

Cautions and Pitfalls

• Avoid using antipsychotics as first-line treatment for agitation, as they carry an FDA black box warning for increased mortality in elderly patients with dementia 1
• Be aware that donepezil has been associated with rare cases of mania, particularly when titrated from 5 mg to 10 mg daily 6
• Recognize that abrupt discontinuation rather than gradual tapering may increase the risk of withdrawal symptoms 3
• Understand that cognitive and behavioral deterioration after stopping donepezil may be mistaken for disease progression rather than withdrawal 3