What is Aricept (donepezil)?

Aricept (Donepezil): What It Is and How It Works

Aricept (donepezil) is a reversible acetylcholinesterase inhibitor medication primarily used for treating symptoms of mild, moderate, and severe Alzheimer's disease by enhancing cholinergic function in the brain. 1

Mechanism of Action

Donepezil works by:

• Inhibiting the enzyme acetylcholinesterase, which breaks down acetylcholine in the brain
• Increasing acetylcholine concentration in the brain, which helps compensate for the loss of functioning cholinergic neurons
• Enhancing cholinergic neurotransmission, addressing some of the cognitive symptoms of Alzheimer's disease 1

The drug does not alter the underlying disease process or stop the progression of Alzheimer's disease, but it can temporarily improve or stabilize symptoms.

Formulation and Administration

Donepezil is available as:

• Oral tablets in 5 mg and 10 mg strengths
• Once-daily dosing (typically at bedtime)
• Film-coated tablets containing inactive ingredients including lactose monohydrate, microcrystalline cellulose, and other excipients 1

Dosing Regimen

The standard dosing protocol for Aricept is:

• Initial dose: 5 mg once daily
• After 4-6 weeks, can be increased to 10 mg once daily if well tolerated
• For moderate to severe Alzheimer's disease: May be increased to 23 mg daily after at least 3 months on 10 mg daily 2

Clinical Efficacy

Clinical trials have demonstrated that donepezil:

• Improves cognitive function as measured by standardized tests (ADAS-Cog, MMSE)
• Enhances global clinical function based on clinician assessment
• Shows modest improvements in activities of daily living
• Provides benefits in behavioral symptoms 3, 4

In clinical studies, donepezil showed statistically significant improvements compared to placebo:

• 2.5-3.1 point improvement on ADAS-Cog scale
• 32-38% of patients showed clinical improvement on global assessment scales 3

Side Effects

Common side effects include:

• Gastrointestinal issues: nausea, vomiting, diarrhea (most common)
• Insomnia and abnormal dreams
• Muscle cramps
• Fatigue and dizziness
• Anorexia 5, 6

These side effects are typically mild to moderate and often transient. Taking the medication with food can help reduce gastrointestinal side effects.

Important Clinical Considerations

• Assessment of response: Beneficial response should be evaluated after 6-12 months of treatment through physician assessment, caregiver reports, neuropsychological testing, and functional changes 5

• Discontinuation: Consider stopping the medication if:

  • Side effects develop and don't resolve
  • Poor medication adherence
  • Continued deterioration at pre-treatment rate after 6-12 months 5, 2

• Pharmacokinetics:

  • Long half-life of approximately 70 hours
  • Reaches steady state within 15 days
  • Highly protein-bound (96%) 1, 7

• Drug interactions:

  • Limited significant drug interactions
  • Metabolized by CYP450 enzymes 2D6 and 3A4 1

Advantages Over Earlier Cholinesterase Inhibitors

Unlike tacrine (an earlier cholinesterase inhibitor):

• No hepatotoxicity (tacrine caused liver enzyme elevation in 40% of patients)
• Once-daily dosing (versus four times daily for tacrine)
• Better safety profile 5, 3

Clinical Pearls

• Brief mental status tests may be relatively insensitive for measuring donepezil's cognitive effects
• Patients who don't respond to one cholinesterase inhibitor may respond to another
• Donepezil provides modest improvement or stabilization rather than dramatic improvement
• Rapid dose escalation can lead to increased side effects 2

Donepezil represents an important treatment option for managing symptoms of Alzheimer's disease, with established efficacy and a favorable safety profile compared to earlier medications in its class.