What are the recommended medications for treating dementia?

Recommended Medications for Treating Dementia

Cholinesterase inhibitors (ChEIs) and memantine are the first-line pharmacological treatments for dementia, with donepezil being the preferred initial medication due to its once-daily dosing and efficacy across mild to severe Alzheimer's disease. 1

First-Line Medications by Dementia Type and Severity

Mild to Moderate Alzheimer's Disease

• Donepezil: Start at 5 mg once daily, target dose 10 mg once daily 1
• Rivastigmine: Start at 1.5 mg twice daily, target dose 3-6 mg twice daily 1, 2
• Galantamine: Start at 4 mg twice daily, target dose 8-12 mg twice daily 1, 3

Moderate to Severe Alzheimer's Disease

• Donepezil: 5-10 mg daily, with option to increase to 23 mg daily after at least 3 months on 10 mg 1
• Memantine: Indicated specifically for moderate to severe Alzheimer's disease 4
• Combination therapy: Memantine plus donepezil for moderate to severe disease 1

Medication Selection Algorithm

1. Initial selection:

   • Choose donepezil for most patients due to simpler once-daily dosing and longer half-life (70-80 hours) 1, 5
   • Consider rivastigmine for patients with mixed Alzheimer's and Parkinson's disease dementia 2

2. Dosing titration:

   • Donepezil: Start at 5 mg once daily for 4-6 weeks, then increase to 10 mg if tolerated 1
   • Rivastigmine: Start at 1.5 mg twice daily, increase by 1.5 mg twice daily every 2 weeks to target dose 2
   • Galantamine: Start at 4 mg twice daily, increase by 4 mg twice daily every 4 weeks to target dose 1

3. Monitoring response:

   • Evaluate after 6-12 months for stabilization or slowing of cognitive decline 1
   • Look for improvements in functional abilities and behavioral changes
   • Consider caregiver reports of improvement

Managing Side Effects

• Common cholinergic side effects (7-30% incidence) include 1, 5:

  • Gastrointestinal symptoms (nausea, vomiting, diarrhea)
  • Dizziness
  • Headache

• If side effects occur:

  • Temporarily discontinue for several doses
  • Restart at same or lower dose level
  • If interrupted for >3 days, restart at lowest dose and retitrate 2

• Monitor for bradycardia with donepezil in patients with cardiovascular history 1

When to Discontinue Treatment

Discontinue ChEIs or memantine if 6:

1. Clinically meaningful worsening of dementia over past 6 months not attributable to other medical conditions
2. No clinically meaningful benefit observed at any time during treatment
3. Development of severe or end-stage dementia
4. Intolerable side effects
5. Poor medication adherence

Important exception: Do not discontinue ChEIs in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 6

Deprescribing Protocol

When discontinuing medication 6:

1. Reduce dose by 50% every 4 weeks until reaching initial starting dose
2. After 4 weeks at starting dose, discontinue completely
3. Monitor for worsening and reinitiate if clinically meaningful decline occurs

Special Considerations

• Continue treatment in patients who have had meaningful reduction in neuropsychiatric symptoms even with cognitive/functional decline 6
• Deprescribe ChEIs and memantine for individuals with mild cognitive impairment 6
• For patients with non-Alzheimer's dementia types (e.g., frontotemporal dementia), ChEIs and memantine should be discontinued 6

Efficacy Expectations

• Modest benefits on cognitive function, with average improvements of 2-5 points on cognitive assessment scales 7, 8
• Stabilization or slowing of cognitive decline rather than reversal of symptoms
• Benefits may be maintained for approximately 21 to 81 weeks with ongoing treatment 9

ChEIs and memantine remain the mainstay of pharmacological treatment for dementia, with the understanding that they provide symptomatic relief rather than disease modification. Careful monitoring, appropriate dose titration, and management of side effects are essential to maximize benefit and minimize harm.