Discontinuation of Donepezil in Patients with Alzheimer's Disease and Other Dementias

Introduction to Tapering

The American College of Physicians and other medical societies recommend tapering donepezil gradually over 2-4 weeks rather than abruptly discontinuing to minimize withdrawal symptoms and prevent cognitive deterioration in patients with Alzheimer's disease and other dementias 1

Tapering donepezil is recommended to prevent acute cognitive decline, reduce withdrawal symptoms, and avoid cholinergic rebound effects, which can be detrimental to patient outcomes 1
Abrupt discontinuation of donepezil can cause a sudden decrease in acetylcholine levels, leading to cholinergic rebound effects, similar to the rebound acid hypersecretion seen with other medications like PPIs 2

The Mayo Clinic recommends tapering cholinesterase inhibitors, such as donepezil, over 2-4 weeks after obtaining agreement with family, with a suggested tapering schedule of reducing the dose by half for 2 weeks before discontinuation 1
For patients on 10 mg daily, the recommended tapering schedule is to reduce to 5 mg daily for 2 weeks before discontinuation, and for patients on 5 mg daily, consider alternate-day dosing for 2 weeks before discontinuation 1

Monitoring is crucial during and after donepezil tapering, including assessing cognitive function, functional status, and behavioral symptoms, to identify any worsening of symptoms or emergence of new symptoms 1

Consider discontinuing donepezil when no perceived benefit is achieved in the first 3 months of treatment, the patient's dementia has progressed to very advanced stages, or intolerable side effects occur despite dose adjustments 1

The principle of gradual discontinuation applies to many neurologically active medications, including antipsychotics, benzodiazepines, and disease-modifying antirheumatic drugs (DMARDs), to prevent withdrawal symptoms and rebound effects 1, 3, 4
Antipsychotics require tapering over periods greater than 1 month to prevent withdrawal symptoms, benzodiazepines need gradual tapering to prevent rebound anxiety and withdrawal, and DMARDs require gradual discontinuation over abrupt discontinuation 1, 3, 4