Management of Donepezil and Memantine in Patients with Anxiety and Sundowning

Understanding the Clinical Picture

The American Academy of Family Physicians does not list sustained anxiety as a side effect of donepezil, and initial agitation typically resolves within a few weeks 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 shows benefits in quality of life, with less agitation reported in treatment groups compared to placebo, according to the American Academy of Neurology 2

Discontinue donepezil in advanced dementia, as it lacks long-term benefit, particularly in severe disease, as recommended by the American Geriatrics Society 3
Consider discontinuation if no clinical benefit is observed during treatment, or if clinically meaningful worsening of dementia occurs over 6 months without other contributing factors, as suggested by the American Academy of Neurology 2

The actual adverse effects of donepezil include nausea, vomiting, diarrhea, nightmares, and bradyarrhythmias, according to the Mayo Clinic Proceedings and the American College of Clinical Pharmacology 4, 3

Use gradual tapering rather than abrupt cessation to avoid potential rebound worsening of cognitive or behavioral symptoms, as recommended by the American Academy of Neurology 3
Reduce the dose by 50% every 4 weeks until reaching the initial starting dose, according to the American Geriatrics Society 2

The combination of donepezil and memantine produces significant benefits on global clinical status measures, improvements in neuropsychiatric symptoms, and reduced caregiver distress, as reported by the American Academy of Neurology 2
Adding memantine to stable donepezil therapy provides additional benefit in patients with moderate to severe Alzheimer's disease, according to the American College of Clinical Pharmacology 2

The most common error is attributing behavioral symptoms to the medication when they are actually manifestations of disease progression or environmental factors, as warned by the American Academy of Family Physicians 1
Systematically evaluate for delirium triggers, medication interactions, pain, infection, or changes in the patient's environment before discontinuing effective therapy, as recommended by the Mayo Clinic Proceedings and the American Geriatrics Society 4, 1