Memantine (Namenda) Dosing for Moderate to Severe Alzheimer's Disease
The recommended dosing regimen for memantine (Namenda) in moderate to severe Alzheimer's disease is to start at 5 mg once daily and titrate by 5 mg weekly to a target dose of 20 mg/day (given as 10 mg twice daily), which is the FDA-approved effective dose. 1
Initial Dosing and Titration Schedule
- Starting dose: 5 mg (2.5 mL) once daily
- Titration: Increase in 5 mg increments at weekly intervals
- Week 2: 10 mg/day (5 mg twice daily)
- Week 3: 15 mg/day (5 mg and 10 mg as separate doses)
- Week 4: 20 mg/day (10 mg twice daily) - maintenance dose 1
The minimum recommended interval between dose increases is one week to minimize side effects and ensure tolerability. 1
Administration Guidelines
- Memantine can be taken with or without food
- Do not mix the oral solution with any other liquid
- If doses are missed for several days, restart at a lower dose and re-titrate as described above
- For patients with difficulty swallowing, the extended-release capsules can be opened and contents sprinkled on applesauce 2
Special Populations
- Severe renal impairment (creatinine clearance 5-29 mL/min): Reduce target dose to 5 mg twice daily (10 mg/day total) 1
- Hepatic impairment: Administer with caution in severe hepatic impairment 1
Extended-Release Option
An extended-release formulation (Namenda XR) is available as a once-daily 28 mg capsule, which may improve medication adherence in patients with difficulty following twice-daily regimens. 2, 3
- The extended-release formulation follows a similar titration schedule but reaches a higher final dose (28 mg once daily)
- This formulation may be particularly beneficial for improving adherence in patients with moderate to severe Alzheimer's disease 3
Efficacy and Clinical Evidence
Memantine has demonstrated effectiveness for moderate to severe Alzheimer's disease:
- Memantine shows statistically significant improvement in cognition for moderate to severe Alzheimer's disease 4
- It is effective as both monotherapy and in combination with cholinesterase inhibitors like donepezil 5
- For moderate to severe Alzheimer's disease, the American Academy of Neurology recommends donepezil 5-10 mg daily with the option to add memantine for combination therapy 6
Monitoring and Side Effects
- Most common adverse events (≥5% and greater than placebo): dizziness, headache, confusion, and constipation 1
- Withdrawal rates due to adverse events are similar to placebo (approximately 10-11.5%) 1
- Monitor conditions that raise urine pH, as they may decrease urinary elimination of memantine, resulting in increased plasma levels 1
Treatment Duration and Discontinuation
Continue treatment in patients who show meaningful reduction in neuropsychiatric symptoms even with cognitive/functional decline 6
Consider discontinuation if there is:
- Clinically meaningful worsening of dementia
- No clinically meaningful benefit
- Development of severe or end-stage dementia
- Intolerable side effects
- Poor medication adherence 6
When discontinuing, reduce dose by 50% every 4 weeks until reaching the initial starting dose, then discontinue completely 6
Do not discontinue in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 6
Memantine is currently the only approved NMDA receptor antagonist for the treatment of moderate to severe Alzheimer's disease and has shown benefits in global status, cognition, function, and behavior when used appropriately at the recommended dosage.