What are the recommended medications and dosages for treating dementia, specifically Alzheimer's disease?

Recommended Medications for Alzheimer's Disease

For patients with mild to moderate Alzheimer's disease, first-line treatment should be a cholinesterase inhibitor (ChEI) - specifically donepezil, rivastigmine, or galantamine - as these medications provide modest cognitive and functional benefits while being generally well-tolerated. 1

First-Line Medications and Dosing

Donepezil (Aricept)

• Starting dose: 5 mg once daily
• Titration: After 4-6 weeks, may increase to 10 mg once daily if well tolerated
• Advantages: Once-daily dosing, not hepatotoxic, simplest titration schedule
• Common side effects: Mild nausea, vomiting, diarrhea (can be reduced by taking with food)
• Special considerations: May cause initial increase in agitation that typically subsides after a few weeks 1

Rivastigmine (Exelon)

• Starting dose: 1.5 mg twice daily (3 mg/day)
• Titration: Increase by 1.5 mg twice daily every 4 weeks as tolerated
• Maximum dose: 6 mg twice daily (12 mg/day)
• Common side effects: Nausea, vomiting, diarrhea, headaches, dizziness, abdominal pain
• Special considerations: Take with food; contraindicated with aminoglycosides and procainamide 1, 2

Galantamine (Reminyl)

• Starting dose: 4 mg twice daily with morning and evening meals
• Titration: After 4 weeks, increase to 8 mg twice daily; after another 4 weeks, may consider 12 mg twice daily based on clinical benefit and tolerability
• Common side effects: Nausea, vomiting, diarrhea
• Special considerations: Contraindicated in hepatic or renal impairment; take with meals 1, 3

Second-Line Medication

Tacrine (Cognex)

• Not recommended as first-line due to:
  • Hepatotoxicity in 40% of patients (requires biweekly liver tests)
  • Four-times-daily dosing schedule
  • High incidence of side effects 1

Assessment of Response

• Beneficial response should be assessed after 6-12 months of treatment
• Look for:
  • Stabilization or delayed deterioration of cognitive or behavioral problems
  • Physician's global assessment
  • Primary caregiver's report
  • Neuropsychologic assessment or mental status questionnaire
  • Evidence of behavioral or functional changes 1

When to Discontinue Treatment

ChEIs should be discontinued if:

1. Side effects develop and do not resolve
2. Adherence is poor
3. Deterioration continues at the pretreatment rate after 6-12 months
4. Patient has severe or end-stage dementia (dependence in most basic ADLs, inability to respond to environment) 1

Important Clinical Considerations

• Patients who do not respond to one ChEI may respond to another
• Brief mental status tests are relatively insensitive measures of ChEI effects
• The most that these drugs can achieve is to modify the manifestations of Alzheimer's disease - they do not alter disease progression 1, 4
• ChEIs should not be discontinued in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 1
• Vitamin E (2,000 IU daily) may be considered as an adjunctive treatment to slow functional decline 1

Common Pitfalls to Avoid

1. Unrealistic expectations: Communicate the modest expected benefits to patients and families before starting treatment
2. Rapid titration: Gradual dose increases minimize adverse effects
3. Premature discontinuation: Allow adequate time (6-12 months) to assess response
4. Inappropriate use: ChEIs and memantine should be deprescribed for individuals with mild cognitive impairment 1
5. Inadequate monitoring: Regular assessment of cognitive, functional, and behavioral symptoms is essential

Evidence Quality Considerations

While there are no head-to-head studies comparing the efficacy of the three main ChEIs, the differences between them primarily relate to their side effect profiles and administration regimens 4. Donepezil may have fewer adverse effects compared to rivastigmine, but careful titration can improve tolerability of all agents 4.