What is the recommended titration schedule for donepezil (Aricept) and memantine in patients with dementia and delirium when continuing at the fastest recommended titrations?

Recommended Titration Schedule for Donepezil and Memantine in Dementia and Delirium

The standard titration schedule for donepezil should be 5 mg once daily for 4-6 weeks, then increased to 10 mg once daily if tolerated; while memantine should be started at 5 mg daily and increased by 5 mg weekly until reaching the target dose of 20 mg daily. 1

Donepezil (Aricept) Titration

Standard Titration Schedule

• Initial dose: 5 mg once daily
• Duration at initial dose: 4-6 weeks
• Target dose: 10 mg once daily (optimal therapeutic dose)
• Method: Increase to 10 mg only after tolerability is confirmed at the lower dose 1

Important Considerations

• Rapid titration increases risk of adverse events (nausea, vomiting, diarrhea) without improving rehabilitation outcomes 1
• Gastrointestinal side effects are dose-dependent and more common during dose escalation 2
• For patients with moderate to severe dementia who may need higher doses:
  • Dose titration before escalating to higher doses (e.g., 23 mg) shows better safety profile for cholinergic adverse events 3
  • Consider intermediate titration steps (e.g., alternating 10 mg and higher dose) for 4 weeks before full escalation 3

Memantine Titration

Standard Titration Schedule

• Week 1: 5 mg once daily
• Week 2: 10 mg once daily (5 mg twice daily for immediate-release)
• Week 3: 15 mg once daily (5 mg and 10 mg in divided doses for immediate-release)
• Week 4: 20 mg once daily (10 mg twice daily for immediate-release) 1

Important Considerations

• Slower titration may be necessary in patients with renal impairment 1
• Rapid titration of memantine may precipitate or worsen delirium, particularly in vulnerable patients 1
• Benefits typically become apparent within 3 months of treatment 1

Combination Therapy Considerations

When using both medications together:

• Start and titrate one medication first, stabilize for 4-6 weeks before adding the second medication
• For patients with moderate to severe Alzheimer's disease, combination therapy shows superior outcomes compared to monotherapy 1, 4
• Lower-dose donepezil (5 mg/day) with memantine may have fewer adverse effects while maintaining efficacy compared to higher-dose combinations 4

Special Considerations for Patients with Delirium

• Stabilize delirium before initiating or adjusting cholinesterase inhibitors or memantine 1
• Donepezil treatment may be associated with reduced delirium in critically ill dementia patients 5
• Monitor for drug interactions that may exacerbate delirium (e.g., memantine with trimethoprim can cause myoclonus and delirium) 6

Monitoring During Titration

• Assess for common adverse events:
  • Donepezil: nausea, vomiting, diarrhea, dizziness, headache, insomnia
  • Memantine: headache, dizziness, confusion, constipation
• If adverse events occur, consider temporary dose reduction rather than discontinuation
• If dose reduction is needed during deprescribing, follow guidelines for reducing dose by 50% every 4 weeks until reaching the initial starting dose 2

Following these titration schedules will maximize therapeutic benefit while minimizing adverse effects in patients with dementia and delirium.