What is the dosage and indication of Memantine for Alzheimer's disease?

Memantine for Alzheimer's Disease: Dosage and Indications

Memantine is indicated for the treatment of moderate to severe dementia of the Alzheimer's type, with a recommended target dose of 20 mg/day administered as 10 mg twice daily. 1

Indications

Memantine is specifically approved for:

• Moderate to severe Alzheimer's disease
• Can be used as monotherapy or in combination with cholinesterase inhibitors

Memantine is not indicated for mild Alzheimer's disease, as evidence suggests there is probably no significant clinical benefit in this population. 2

Dosing Protocol

The FDA-approved dosing regimen for memantine is:

1. Initial dose: 5 mg once daily
2. Titration: Increase in 5 mg increments at weekly intervals
3. Target dose: 20 mg/day (10 mg twice daily)
4. Titration schedule:
   • Week 1: 5 mg once daily
   • Week 2: 10 mg/day (5 mg twice daily)
   • Week 3: 15 mg/day (5 mg in morning, 10 mg in evening)
   • Week 4 and beyond: 20 mg/day (10 mg twice daily) 1

Special Populations

• Severe renal impairment: Reduce target dose to 5 mg twice daily (10 mg/day total) for patients with creatinine clearance of 5-29 mL/min 1
• Severe hepatic impairment: Administer with caution 1

Administration

• Can be taken with or without food
• If doses are missed for several days, restart at lower dose and re-titrate
• Do not mix oral solution with other liquids 1

Efficacy

Memantine shows consistent benefits in moderate to severe Alzheimer's disease:

• Cognition: 3.11 point improvement on the Severe Impairment Battery scale 2
• Activities of daily living: 1.09 point improvement on ADL19 scale 2
• Behavior and mood: 1.84 point improvement on Neuropsychiatric Inventory 2
• Global clinical status: 0.21 point improvement on CIBIC+ 2

When combined with donepezil (a cholinesterase inhibitor), memantine provides superior outcomes compared to donepezil alone in:

• Cognition
• Activities of daily living
• Behavior
• Global function 3, 4

Safety and Tolerability

Memantine is generally well-tolerated with fewer side effects than cholinesterase inhibitors. Common adverse events include:

• Dizziness (6.1% vs 3.9% for placebo) 2
• Headache (5.5% vs 4.3% for placebo) 2
• Confusion and constipation 1

The discontinuation rate due to adverse events is similar to placebo (7.4% vs 12.4%) 4

Monitoring Treatment Response

Response to memantine should be assessed after 3-6 months of treatment, looking for:

• Stabilization or slowing of cognitive decline
• Maintenance of activities of daily living
• Improvement or stabilization in behavioral symptoms 3

Common Pitfalls to Avoid

1. Inappropriate patient selection: Memantine is not indicated for mild Alzheimer's disease
2. Inadequate dose titration: Follow the recommended weekly titration schedule
3. Premature discontinuation: Benefits may take several weeks to become apparent
4. Unrealistic expectations: Memantine slows progression but does not reverse the disease 3
5. Failure to adjust dose in renal impairment: Patients with severe renal impairment require dose reduction

In summary, memantine is an effective N-methyl-D-aspartate (NMDA) receptor antagonist that provides modest but clinically meaningful benefits in moderate to severe Alzheimer's disease, either as monotherapy or in combination with cholinesterase inhibitors.