What are the recommended medications for treating Alzheimer's disease?

Recommended Medications for Alzheimer's Disease

First-Line Treatment: Donepezil

Start donepezil 5 mg once daily as first-line pharmacotherapy for mild to moderate Alzheimer's disease, increasing to 10 mg daily after 4-6 weeks if tolerated. 1, 2, 3

Donepezil is the preferred initial cholinesterase inhibitor due to several practical advantages 1, 2:

• Once-daily dosing (compared to twice-daily for alternatives)
• Favorable side effect profile
• No hepatotoxicity (unlike tacrine)
• Established efficacy across all disease stages (mild, moderate, and severe)

Dosing Strategy

• Initial dose: 5 mg once daily for at least 4-6 weeks 1, 2, 3
• Maintenance dose: Increase to 10 mg once daily after the initial period if well-tolerated 1, 2, 3
• Administration: Take with food to minimize gastrointestinal side effects 2

Alternative Cholinesterase Inhibitors

If donepezil is not tolerated or contraindicated, consider these alternatives:

Rivastigmine

• Starting dose: 1.5 mg twice daily with food 1, 2
• Titration: Increase by 1.5 mg twice daily every 4 weeks as tolerated 1, 2
• Maximum dose: 6 mg twice daily (12 mg per day) 1, 2
• Note: Take with food to reduce adverse effects 2

Galantamine

• Starting dose: 4 mg twice daily with morning and evening meals 1, 2, 4
• Titration: Increase to 8 mg twice daily after 4 weeks 1, 2
• Maximum dose: May increase to 12 mg twice daily based on individual tolerability 1, 2

Moderate to Severe Disease: Add Memantine

Add memantine 20 mg/day when patients progress to moderate or severe Alzheimer's disease. 1, 2, 3

• Memantine shows statistically significant improvement in cognition 1, 2, 3
• Can be used alone or in combination with cholinesterase inhibitors 1, 2, 3
• Particularly beneficial for patients with MMSE scores in the 1-10 range 5

Monitoring Treatment Response

Allow 6-12 months to properly assess treatment benefit before considering discontinuation. 1, 2, 3

Use comprehensive assessments including 1, 2, 3:

• Physician's global assessment
• Primary caregiver's report of functional and behavioral changes
• Neuropsychological testing (ADAS-cog, MMSE, SIB)
• Evidence of behavioral or functional changes

Expected Treatment Effects

• Realistic expectation: 5-15% benefit over placebo 1
• Equivalent to delaying decline by approximately one year 1
• ADAS-cog improvement of 2-3 points on the 70-point scale 6
• Treatment effects abate within 6 weeks of discontinuation 5

Managing Side Effects

Common adverse effects are cholinergic in nature, occurring in 7-30% of patients 2, 3, 7:

• Nausea, vomiting, diarrhea
• Dizziness, abdominal pain
• Headaches and fatigue
• Generally mild and transient 2, 3

Strategies to Minimize Side Effects 2, 3:

• Take medication with food
• Use slower dose titration
• Consider switching to a different cholinesterase inhibitor if side effects persist

Important: Patients are more likely to withdraw from treatment (24% vs 20% placebo) and experience adverse events (72% vs 65% placebo) 6

Comprehensive Management Approach

Develop a comprehensive management plan immediately upon diagnosis that addresses 1, 2, 3:

• Patient and family values, preferences, and comorbid conditions
• Realistic expectations for drug therapy
• Future care choices and advance planning
• Driving safety, financial planning, and healthcare directives

Nonpharmacologic Interventions

Implement alongside medication throughout the disease course 1, 2, 3:

• Provide predictable routines and simplify tasks
• Create a safe environment with orientation aids (calendars, labels)
• Referrals to social service agencies and support resources
• Caregiver education and support groups
• Day care programs and Alzheimer's Association Safe Return Program registration

Behavioral Symptoms

Exhaust nonpharmacologic interventions before adding medications for behavioral symptoms. 3

When behavioral disturbances persist despite cholinesterase inhibitor therapy and nonpharmacologic interventions 2:

• Use of a psychotropic agent may be necessary
• Start with low doses and increase slowly
• Monitor carefully for side effects

Special Considerations

Rapid Cognitive Decline

• Occurs in up to one-third of patients, more common in moderate dementia 2
• Patients with rapid cognitive decline may achieve greater benefits from rivastigmine and galantamine 2

Vitamin E

• Vitamin E (2,000 IU daily) may slow the progression of functional symptoms 2
• Based on expert consensus, though evidence is limited 2

Dose Comparisons

• The 10 mg/day dose of donepezil provides marginally larger benefits than 5 mg/day 6
• The 23 mg/day dose shows no greater benefits than 10 mg/day but has higher withdrawal rates and adverse events 6
• No evidence of differences in efficacy between donepezil, galantamine, and rivastigmine 8