What is the initial medication for dementia, specifically Alzheimer's disease?

Initial Medication for Dementia (Alzheimer's Disease)

Donepezil is recommended as the first-line medication for patients with Alzheimer's disease, starting at 5 mg once daily with a target dose of 10 mg once daily. 1

Pharmacological Management Algorithm

First-Line Treatment

• Donepezil
  • Initial dose: 5 mg once daily
  • Target dose: 10 mg once daily
  • Titration: Increase to 10 mg after at least 3 months if well tolerated
  • For moderate to severe AD: Consider increasing to 23 mg daily after at least 3 months on 10 mg 1

Alternative First-Line Options

• Rivastigmine

  • Initial dose: 1.5 mg twice daily
  • Target dose: 3-6 mg twice daily
  • Titration: Increase dose after a minimum of 2 weeks at each dose level 1, 2
  • Should be taken with meals in divided doses 2

• Galantamine

  • Initial dose: 4 mg twice daily
  • Target dose: 8-12 mg twice daily
  • Titration: Gradually increase if tolerated 1

For Moderate to Severe Alzheimer's Disease

• Consider adding Memantine to cholinesterase inhibitor therapy
  • Initial dose: 5 mg once daily
  • Increase in 5 mg increments to target dose of 10 mg twice daily
  • Minimum of 1 week between dose increases 1, 3
  • For severe renal impairment: 5 mg twice daily 3

Monitoring and Side Effect Management

Common Side Effects to Monitor

• Cholinergic side effects (7-30% incidence) 1:
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea)
  • Dizziness
  • Headache

Special Considerations

• Monitor for bradycardia with donepezil in patients with cardiovascular history 1
• Conditions that raise urine pH may decrease memantine elimination, resulting in increased plasma levels 3
• Weight loss should be monitored as a potential treatment-related adverse effect 4

Evidence Quality and Comparative Efficacy

The recommendation for donepezil as first-line therapy is supported by extensive clinical evidence. Cochrane reviews have demonstrated that donepezil produces improvements in cognitive function and global clinical state in patients with mild to moderate Alzheimer's disease 5, 6.

Donepezil has shown benefits in:

• Cognitive function (measured by ADAS-Cog, MMSE, and SIB scales)
• Activities of daily living
• Global clinical function
• Delaying symptomatic progression 5, 7

Higher doses of donepezil (10 mg vs 5 mg) show marginally better efficacy but with increased adverse events 5. The 23 mg dose may provide additional benefits for language and visuospatial ability in moderate to severe AD 8, but has more side effects than the 10 mg dose 5.

Important Clinical Considerations

• Begin treatment early after diagnosis for maximum benefit
• Ensure adequate titration periods between dose increases to minimize side effects
• Consider discontinuing cholinesterase inhibitors if:
  • No clinically meaningful benefit observed
  • Development of severe or end-stage dementia
  • Intolerable side effects
  • Poor medication adherence 1
• Do not discontinue in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 1
• When discontinuing, reduce dose by 50% every 4 weeks until reaching initial starting dose, then discontinue completely 1

Remember that pharmacological treatment should be combined with non-pharmacological interventions such as cognitive stimulation therapy, physical exercise, environmental modifications, and caregiver support for optimal management of Alzheimer's disease 1.