Initial Treatment for Alzheimer's Disease
Donepezil is recommended as the first-line medication for patients with Alzheimer's disease, starting at 5 mg once daily and targeting 10 mg once daily. 1
Pharmacological Management
First-Line Treatment: Donepezil
- Start with 5 mg once daily
- After at least 3-4 weeks, if well tolerated, increase to target dose of 10 mg once daily
- For moderate to severe Alzheimer's disease, may consider increasing to 23 mg daily after at least 3 months on 10 mg 1, 2
- Donepezil has a long elimination half-life (70-80 hours), allowing for convenient once-daily dosing 3
Alternative First-Line Options
If donepezil is not tolerated or contraindicated, consider:
- Rivastigmine: Start with 1.5 mg twice daily, titrate gradually to 3-6 mg twice daily 1, 4
- Galantamine: Start with 4 mg twice daily, titrate gradually to 8-12 mg twice daily 1
Dosing Summary
| Medication | Starting Dose | Target Dose | Administration |
|---|---|---|---|
| Donepezil | 5 mg once daily | 10 mg once daily | Once daily |
| Rivastigmine | 1.5 mg twice daily | 3-6 mg twice daily | With meals, twice daily |
| Galantamine | 4 mg twice daily | 8-12 mg twice daily | Twice daily |
Managing Side Effects
Cholinergic side effects occur in 7-30% of patients and include 1, 3:
- Gastrointestinal symptoms (nausea, vomiting, diarrhea)
- Dizziness
- Headache
Important precaution: Monitor for potential bradycardia with donepezil in patients with cardiovascular history 1
Titration strategy: Slower titration can reduce side effects, particularly with rivastigmine 3
Non-Pharmacological Interventions
These should be implemented alongside medication:
Daily routines: Establish predictable routines for meals, exercise, and bedtime 1
Task simplification: Break complex tasks into simple steps 1
Environmental modifications:
- Install safety locks on doors and gates
- Use color-coded or graphic labels as orientation cues
- Install grab bars in bathrooms
- Reduce excess stimulation and clutter
- Ensure adequate lighting 1
Cognitive stimulation: Group cognitive stimulation therapy for mild to moderate dementia 1
Physical exercise: Group or individual physical exercise to improve physical and cognitive function 1
Caregiver Support
- Provide psychosocial and psychoeducational interventions for caregivers 1
- These interventions are essential to reduce caregiver burden and improve patient outcomes
Comparative Effectiveness
- The three cholinesterase inhibitors (donepezil, rivastigmine, galantamine) show similar efficacy for mild to moderate Alzheimer's disease 5
- Donepezil appears to have fewer adverse effects compared to rivastigmine 5
- Donepezil has simpler titration than rivastigmine and galantamine 5
Treatment Monitoring and Discontinuation
Consider discontinuing cholinesterase inhibitors if:
- Clinically meaningful worsening of dementia
- No clinically meaningful benefit
- Development of severe or end-stage dementia
- Intolerable side effects
- Poor medication adherence 1
Important: Do not discontinue cholinesterase inhibitors in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 1
When discontinuing medication, reduce dose by 50% every 4 weeks until reaching initial starting dose, then discontinue completely 1