What medications are recommended to treat Alzheimer's disease?

Medications for Alzheimer's Disease Treatment

Donepezil is recommended as first-line therapy for mild to moderate Alzheimer's disease, while memantine is indicated for moderate to severe Alzheimer's disease, with combination therapy often providing additional benefit in moderate to severe cases. 1, 2, 3

First-Line Treatment Options

For Mild to Moderate Alzheimer's Disease:

• Cholinesterase Inhibitors (ChEIs):
  • Donepezil: Start at 5 mg once daily, titrate to 10 mg once daily after 4-6 weeks if tolerated 1
  • Rivastigmine: Start at 1.5 mg twice daily, titrate to 3-6 mg twice daily 1
  • Galantamine: Start at 4 mg twice daily, titrate to 8-12 mg twice daily 1

For Moderate to Severe Alzheimer's Disease:

• Memantine: FDA-approved specifically for moderate to severe Alzheimer's disease 2
• Combination therapy: Adding memantine to a cholinesterase inhibitor (particularly donepezil) for moderate to severe disease 1

Medication Selection Algorithm

1. Assess disease severity using standardized cognitive assessment tools
2. For mild to moderate disease: Start with donepezil (preferred first-line due to once-daily dosing and established efficacy) 1
3. For moderate to severe disease:
   • Start with donepezil if not already on medication
   • Add memantine if already on a cholinesterase inhibitor 1, 2
4. If intolerance to donepezil: Consider alternative cholinesterase inhibitors (rivastigmine or galantamine) 1

Dosing and Titration

Donepezil:

• Starting dose: 5 mg once daily
• After 4-6 weeks, increase to 10 mg once daily if well tolerated
• Monitor for common side effects: nausea, diarrhea, vomiting, sleep disturbances, and bradycardia 1

Memantine:

• Used specifically for moderate to severe Alzheimer's disease
• Can be used as monotherapy or in combination with a cholinesterase inhibitor 2

Efficacy Assessment

• Evaluate response after 6-12 months of treatment 1
• Look for:
  • Stabilization or slowing of cognitive decline
  • Improvement or stabilization in functional abilities
  • Changes in behavior
  • Caregiver reports of improvement

Discontinuation Considerations

Cholinesterase inhibitors or memantine should be discontinued if 4:

• No clinically meaningful benefit observed during treatment
• Development of severe or end-stage dementia
• Intolerable side effects (confusion, dizziness, falls)
• Poor medication adherence

Important: Do not discontinue cholinesterase inhibitors in patients who currently have clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 4

Special Considerations

• For patients with cardiovascular history, monitor for potential bradycardia with donepezil 1
• For elderly patients, start at low doses and titrate cautiously 1
• When discontinuing medication, reduce dose gradually (50% every 4 weeks) until reaching the initial starting dose, then discontinue after 4 more weeks 4
• Reinitiate treatment if clinically meaningful worsening occurs after discontinuation 4

Non-Pharmacological Approaches

In addition to medication therapy, consider:

• Environmental modifications
• Behavioral management techniques
• Caregiver support and education
• Cognitive training and physical exercise 1

Treatment Pitfalls to Avoid

1. Failing to monitor for side effects: Cholinergic side effects are common and may lead to discontinuation if not managed
2. Abrupt discontinuation: Can lead to rapid worsening; always taper gradually
3. Not reassessing efficacy: Regular assessment of cognitive and functional status is essential
4. Overlooking caregiver burden: Provide comprehensive psychoeducational training for caregivers 1
5. Continuing treatment without benefit: If no clinically meaningful benefit is observed, consider discontinuation 4

Medications for Alzheimer's disease provide modest but significant benefits for cognition, function, and behavior. Early initiation and appropriate selection based on disease severity can help maximize treatment outcomes and quality of life.