Initial Treatment for Alzheimer's Disease
Start donepezil 5 mg once daily as first-line pharmacotherapy for Alzheimer's disease, then increase to 10 mg daily after 4-6 weeks if tolerated. 1, 2
Why Donepezil is the Preferred Initial Agent
Donepezil is recommended as the first-line cholinesterase inhibitor due to several practical advantages over alternatives 1, 2:
- Once-daily dosing improves medication adherence compared to twice-daily or four-times-daily alternatives 1, 2
- Favorable side effect profile with no hepatotoxicity, unlike tacrine which causes elevated liver enzymes in 49% of patients 3
- Established efficacy across all disease stages from mild to severe Alzheimer's disease 1, 2
- Longer elimination half-life (70-80 hours) allows for stable plasma concentrations with single daily dosing 3
Dosing Strategy
The dosing approach is straightforward 1, 2, 4:
- Start at 5 mg once daily for at least 4-6 weeks
- Increase to 10 mg once daily after the initial period if well-tolerated
- Take with food to minimize gastrointestinal side effects 4
The 4-6 week titration period is critical—studies using a 7-day dose escalation showed higher adverse event rates, which can be minimized by this longer titration schedule 5.
Expected Treatment Benefits
Set realistic expectations with patients and families 2:
- Cognitive improvement of 2-3 points on the ADAS-Cog scale compared to placebo at 24 weeks 6
- This represents approximately 5-15% benefit over placebo, equivalent to delaying decline by about one year 2
- Benefits are maintained for 21-81 weeks with continued treatment 5
- Allow 6-12 months to properly assess treatment benefit before considering discontinuation 1, 2, 4
Adding Memantine for Disease Progression
Add memantine 20 mg/day when patients progress to moderate or severe Alzheimer's disease 1, 2, 4:
- Memantine shows statistically significant improvement in cognition and can be used alone or in combination with cholinesterase inhibitors 1, 2
- The combination of memantine with donepezil provides additional benefit in moderate to severe disease 7
Alternative Cholinesterase Inhibitors
If donepezil is not tolerated, consider alternatives 2, 4:
- Rivastigmine: Start 1.5 mg twice daily with food, increase by 1.5 mg twice daily every 4 weeks as tolerated to maximum 6 mg twice daily 2, 4
- Galantamine: Start 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, may increase to 12 mg twice daily based on tolerability 2, 4
Managing Side Effects
Common cholinergic adverse effects occur in 7-30% of patients but are generally mild and transient 1, 4, 3:
- Nausea, vomiting, diarrhea, dizziness, abdominal pain are most common 1, 4
- Strategies to minimize side effects include taking medication with food, using slower dose titration, and considering switching to a different cholinesterase inhibitor if side effects persist 1
- The 10 mg dose has more adverse effects than 5 mg, but very few patients discontinue treatment as a direct result 5, 6
Essential Nonpharmacologic Interventions
Implement these strategies alongside medication from the time of diagnosis 1, 2, 4:
- Provide predictable routines and simplify tasks 1
- Create a safe environment with calendars and labels for orientation 1
- Refer to social service agencies and support resources 2
- Provide caregiver education and support groups 2
- Consider day care programs and register in the Alzheimer's Association Safe Return Program 1
- Exhaust nonpharmacologic interventions before adding medications for behavioral symptoms 1
Comprehensive Management at Diagnosis
Develop a complete management plan immediately upon diagnosis that addresses 1, 2, 4:
- Patient and family values, preferences, and comorbid conditions 1, 2
- Realistic expectations for drug therapy (5-15% benefit over placebo) 2
- Future care choices and advance planning including driving safety, financial planning, and healthcare directives 2
- Optimization of comorbid conditions, as this can reduce disability and maximize function 1