What medications are used to treat Alzheimer's disease?

Medications for Alzheimer's Disease

Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are the first-line pharmacological treatments for mild to moderate Alzheimer's disease, providing modest cognitive benefits and temporary stabilization of symptoms. 1

First-Line Medications

Cholinesterase Inhibitors

These medications work by inhibiting acetylcholinesterase, thereby increasing acetylcholine levels in the brain, which helps improve cognitive function. The three main options are:

1. Donepezil (Aricept)

   • Dosing: Start at 5 mg once daily, may increase to 10 mg daily after 4-6 weeks 1, 2
   • Advantages: Once-daily dosing, no hepatotoxicity, longer half-life (70-80 hours) 1, 3
   • Side effects: Mild gastrointestinal effects (nausea, vomiting, diarrhea), possible initial increase in agitation 1
   • Administration: Can be taken with food to reduce side effects 1

2. Rivastigmine (Exelon)

   • Dosing: Start at 1.5 mg twice daily, increase by 1.5 mg twice daily every 4 weeks to maximum of 6 mg twice daily (12 mg/day) 1, 4
   • FDA indications: Approved for both Alzheimer's disease and Parkinson's disease dementia 4
   • Side effects: Nausea, vomiting, diarrhea, weight loss, headaches, dizziness 1
   • Administration: Should be taken with meals in divided doses 4

3. Galantamine (Reminyl)

   • Dosing: Start at 4 mg twice daily with meals, increase to 8 mg twice daily after 4 weeks, may increase to 12 mg twice daily based on individual response 1
   • Side effects: Similar to other cholinesterase inhibitors (nausea, vomiting, diarrhea) 1
   • Contraindication: Not for use in patients with hepatic or renal impairment 1

Clinical Considerations

Efficacy

• Cholinesterase inhibitors provide modest benefits, typically a 5-15% improvement over placebo 1
• Benefits include temporary stabilization of cognition, improved function, and reduced behavioral symptoms 1
• Observation for 6-12 months is usually necessary to assess potential benefit 1

Monitoring and Assessment

• Response should be assessed through:
  • Physician's global assessment
  • Primary caregiver's report
  • Neuropsychological assessment or mental status questionnaire
  • Evidence of behavioral or functional changes 1

When to Discontinue

Cholinesterase inhibitors should be discontinued if:

• Side effects develop and do not resolve
• Adherence is poor
• Deterioration continues at the pretreatment rate after 6-12 months of treatment 1

Important Clinical Pearls

1. Set realistic expectations: Before starting treatment, communicate the expected modest benefits to patients and families 1
2. Consider switching medications: Patients who do not respond to one cholinesterase inhibitor may respond to another 1
3. Titrate slowly: Adverse effects can be minimized by gradual dose titration and taking medications with food 1, 3
4. Avoid tacrine: Tacrine is no longer considered first-line treatment due to hepatotoxicity requiring frequent liver function monitoring 1

Adjunctive Treatments

• Vitamin E: Daily intake of 2,000 IU may slow the progression of functional symptoms 1
• Medications to avoid: Insufficient evidence supports the use of NSAIDs or ginkgo biloba 1
• Estrogen: Substantial evidence shows estrogens do not benefit cognitive function after Alzheimer's disease onset 1

Comprehensive Management Approach

Effective management of Alzheimer's disease requires both pharmacologic and nonpharmacologic interventions:

1. Develop a comprehensive management plan that addresses comorbid conditions
2. Provide nonpharmacologic interventions for behavioral symptoms before adding medications
3. Link patients and families to community resources and support services like the Alzheimer's Association
4. Modify the management plan as the disease progresses 1

Remember that while these medications can provide symptomatic relief, they do not alter the underlying disease process. The goal of treatment is to improve quality of life by temporarily stabilizing or slowing cognitive decline and improving function.