What is the recommended dosage of memantine (N-methyl-D-aspartate receptor antagonist) for patients with Alzheimer's disease?

Memantine Dosing for Alzheimer's Disease

The recommended dosing regimen for memantine in Alzheimer's disease is to start at 5 mg once daily and titrate weekly by 5 mg increments to a target dose of 20 mg/day (given as 10 mg twice daily), which is the effective dosage demonstrated in clinical trials. 1

Dosing Schedule and Titration

The FDA-approved dosing schedule for memantine is as follows:

• Week 1: 5 mg once daily
• Week 2: 10 mg/day (5 mg twice daily)
• Week 3: 15 mg/day (5 mg and 10 mg as separate doses)
• Week 4 and beyond: 20 mg/day (10 mg twice daily) - maintenance dose

This gradual titration schedule helps minimize side effects while achieving therapeutic levels 1. Memantine can be taken with or without food.

Special Populations

Renal Impairment

• For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the target dose should be reduced to 10 mg/day (5 mg twice daily) 1

Hepatic Impairment

• Memantine should be administered with caution to patients with severe hepatic impairment 1

Extended-Release Formulation

An extended-release formulation is available as an alternative dosing option:

• 28 mg once daily capsule 2
• May improve medication adherence through once-daily dosing
• Capsules can be opened and contents sprinkled on applesauce for patients with swallowing difficulties 2

Clinical Considerations

Indications

Memantine is specifically indicated for moderate to severe Alzheimer's disease 1. Evidence from the Cochrane database shows a small but consistent clinical benefit in moderate-to-severe AD but no benefit in mild AD 3.

Combination Therapy

Memantine can be used as monotherapy or in combination with cholinesterase inhibitors. The American Academy of Neurology recommends combination therapy with memantine plus donepezil for moderate to severe Alzheimer's disease 4.

Monitoring and Discontinuation

• Evaluate response after 6-12 months of treatment 4

• Consider discontinuation if:

  • No clinically meaningful benefit observed
  • Clinically meaningful worsening of dementia over 6 months
  • Development of severe or end-stage dementia
  • Intolerable side effects (confusion, dizziness, falls)
  • Poor medication adherence 5, 4

• Do not discontinue if patient has clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 5

Common Side Effects

The most common adverse events include dizziness (6.1%), headache (5.5%), and confusion 1, 3. These are generally mild and well-tolerated compared to placebo.

Pitfalls to Avoid

• Do not use memantine for mild cognitive impairment - it should be deprescribed in this population 5, 4
• Do not use memantine for frontotemporal dementia or other non-indicated conditions 4
• If a patient misses several days of memantine, dosing should be resumed at lower doses and retitrated according to the schedule 1
• Do not mix memantine oral solution with other liquids 1
• When discontinuing, reduce dose gradually (by 50% every 4 weeks) until reaching the initial starting dose, then discontinue completely 5

Memantine has also shown efficacy in Parkinson's disease with dementia, using the same dosing regimen as for Alzheimer's disease 6, though this is an off-label use.