Is it better to discontinue donepezil (Aricept) or memantine (Namenda) in a geriatric patient with Alzheimer's disease who is experiencing increased anxiety and worsened sundowning while taking the medication?

Should You Discontinue Donepezil or Memantine for Increased Anxiety and Worsened Sundowning?

Do not discontinue donepezil or memantine based solely on increased anxiety or sundowning, as sustained anxiety worsening is not a recognized adverse effect of these medications, and the initial agitation that can occur with donepezil typically resolves within a few weeks. 1

Understanding the Clinical Picture

Donepezil and Anxiety: Separating Myth from Reality

• Donepezil may cause initial agitation in some patients, but this typically subsides after a few weeks and should not be confused with sustained anxiety worsening. 1
• Sustained anxiety is explicitly not listed as a side effect of donepezil by the American Academy of Family Physicians. 1
• If anxiety or agitation persists beyond the first few weeks of treatment, consider other contributing factors such as disease progression, comorbid conditions, or environmental stressors rather than attributing it solely to donepezil. 1

Memantine's Behavioral Profile

• Memantine actually shows benefits in quality of life, with less agitation reported in treatment groups compared to placebo. 2
• For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms, even with cognitive and functional decline. 2

When to Actually Consider Discontinuation

Appropriate Clinical Scenarios for Stopping These Medications

Discontinue only in these specific circumstances:

• Advanced dementia: Donepezil lacks long-term benefit particularly in advanced dementia and is indicated only for mild to moderate dementia, not severe disease. 3
• No clinical benefit observed: Consider discontinuation if no clinical benefit is observed during treatment. 2
• Clinically meaningful worsening: Consider discontinuation if clinically meaningful worsening of dementia occurs over 6 months without other contributing factors. 2
• Severe or end-stage dementia: Consider discontinuation if the patient progresses to severe or end-stage dementia with dependence in most basic activities of daily living. 2

Recognized Adverse Effects (Not Anxiety or Sundowning)

The actual adverse effects of donepezil include nausea, vomiting, diarrhea, nightmares, and bradyarrhythmias. 4, 3

If You Must Discontinue: The Proper Method

Tapering Protocol

• Use gradual tapering rather than abrupt cessation to avoid potential rebound worsening of cognitive or behavioral symptoms. 3
• Reduce the dose by 50% every 4 weeks until reaching the initial starting dose. 2
• For donepezil specifically, a reasonable schedule is to reduce the dose by half for 2-4 weeks, then discontinue. 3
• Monitor for increased agitation during the first few weeks after discontinuation. 3

What to Monitor After Discontinuation

• Acute worsening of cognition or behavior 3
• Increased agitation or neuropsychiatric symptoms 3
• Changes in functional status 3

The Evidence Supporting Continuation

Combination Therapy Benefits

• The combination of donepezil and memantine produces significant benefits on global clinical status measures, improvements in neuropsychiatric symptoms, and reduced caregiver distress. 2
• Adding memantine to stable donepezil therapy provides additional benefit in patients with moderate to severe Alzheimer's disease. 2
• The combination is well-tolerated with no significant increase in serious adverse events. 2

Individual Drug Efficacy

• Donepezil significantly improves cognition, global clinical function, and activities of daily living in mild to moderate Alzheimer's disease. 5
• Memantine improves cognition and global assessment in moderate to severe Alzheimer's disease. 2

Critical Pitfall to Avoid

The most common error is attributing behavioral symptoms to the medication when they are actually manifestations of disease progression or environmental factors. 1 Before discontinuing effective therapy, systematically evaluate for delirium triggers, medication interactions with other agents (particularly anticholinergics, benzodiazepines, or antipsychotics which genuinely worsen cognition), pain, infection, or changes in the patient's environment. 4