What is the recommended treatment and dosage for Alzheimer's disease using Aricept (donepezil)?

Donepezil (Aricept) Treatment for Alzheimer's Disease

The recommended treatment for Alzheimer's disease with donepezil begins with 5 mg once daily in the evening, with a potential increase to 10 mg daily after 4-6 weeks for mild to moderate disease, and up to 23 mg daily for moderate to severe disease after at least 3 months on 10 mg. 1

Dosing Guidelines

• For mild to moderate Alzheimer's disease:

  • Start with 5 mg once daily in the evening, just prior to retiring 1
  • May increase to 10 mg once daily after 4-6 weeks on the 5 mg dose 1
  • Maximum recommended dose is 10 mg daily 1

• For moderate to severe Alzheimer's disease:

  • Start with 5 mg once daily in the evening 1
  • May increase to 10 mg once daily after 4-6 weeks 1
  • May further increase to 23 mg once daily after at least 3 months on 10 mg 1
  • Maximum recommended dose is 23 mg daily 1

• Administration considerations:

  • Take in the evening, just prior to retiring 1
  • Can be taken with or without food 1
  • The 23 mg tablet should not be split, crushed, or chewed 1

Clinical Benefits and Expectations

• Donepezil provides modest improvement of symptoms, temporary stabilization of cognition, or reduction in the rate of cognitive decline in some patients 2
• Approximately 20-35% of patients show significant improvement on neuropsychologic tests, equivalent to delaying decline by about one year 2
• The average improvement in cognition as measured by ADAS-cog is statistically significant but may not reach clinically significant levels in all patients 3
• Efficacy has been demonstrated for up to 4.9 years in patients with mild to moderate Alzheimer's disease 2

Monitoring Response

• Assess response through:
  • Physician's global assessment 2
  • Caregiver reports 2
  • Cognitive assessments 2
• Observation for 6-12 months is usually necessary to assess potential benefit 2
• Consider discontinuation if:
  • Side effects develop and do not resolve 2
  • Adherence is poor 2
  • Deterioration continues at pre-treatment rate after 6-12 months 2

Side Effects and Management

• Common adverse effects include:
  • Gastrointestinal symptoms: nausea, vomiting, diarrhea 2, 4
  • Muscle cramps, particularly leg cramps 2, 5
  • Insomnia, fatigue, and anorexia 4, 5
• Side effects are dose-dependent, with higher incidence at higher doses 6, 7
• Taking donepezil with food can reduce gastrointestinal side effects 2
• Morning administration may be considered to minimize sleep disturbances 6

Special Considerations

• Unlike tacrine, donepezil is not hepatotoxic and does not require liver function monitoring 2, 5
• Cholinesterase inhibitors may exaggerate succinylcholine-type muscle relaxation during anesthesia 1
• May have vagotonic effects on the sinoatrial and atrioventricular nodes, manifesting as bradycardia or heart block 1
• Patients should be monitored for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers 1
• Use with caution in patients with a history of asthma or obstructive pulmonary disease 1

Practical Recommendations

• Communicate the expected modest benefits to patients and families before initiating treatment 2
• Consider morning administration rather than bedtime dosing to minimize sleep disturbances 6
• Monitor for adverse effects, particularly gastrointestinal symptoms 6
• Higher doses (10 mg vs. 5 mg) may provide slightly better cognitive benefits but come with increased risk of side effects 8
• The 23 mg dose has not shown greater benefits than the 10 mg dose but has higher rates of adverse events 8