Memantine (Namenda) Dosing for Cognitive Decline
The recommended dosing for memantine (Namenda) in patients with cognitive decline is to start at 5 mg once daily, then increase by 5 mg increments weekly to a target dose of 20 mg/day (administered as 10 mg twice daily), which is the effective dosage shown in controlled clinical trials. 1
Dosing Schedule and Titration
Memantine should be titrated gradually according to this schedule:
- 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)
This gradual titration helps minimize potential side effects. The minimum recommended interval between dose increases is one week 1.
Administration Considerations
- Memantine can be taken with or without food
- If a patient misses a single dose, they should not double the next dose
- If treatment is interrupted for several days, dosing should be resumed at lower doses and re-titrated
- For the oral solution formulation (2 mg/mL), do not mix with other liquids 1
Special Populations
Renal Impairment
- For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the recommended target dose is reduced to 5 mg twice daily (10 mg/day total) 1
Hepatic Impairment
- Administer with caution to patients with severe hepatic impairment 1
Extended-Release Formulation Option
For patients who might benefit from once-daily dosing, memantine extended-release (ER) is available as a 28 mg once-daily capsule. This formulation may improve medication adherence and offers the option of opening the capsule and sprinkling contents on applesauce for patients with difficulty swallowing 2.
Clinical Indications
Memantine is specifically indicated for moderate to severe dementia of the Alzheimer's type 1. It is not recommended for mild cognitive impairment, as studies have shown inconsistent benefits in this population 3, 4.
The Canadian Consensus Conference on the Diagnosis and Treatment of Dementia recommends that memantine should be deprescribed for individuals with mild cognitive impairment 3.
Efficacy Considerations
Memantine works as an N-methyl-D-aspartate (NMDA) receptor antagonist that inhibits excessive calcium influx induced by chronic overstimulation of the NMDA receptor 5.
Clinical evidence shows that:
- Memantine is effective for moderate to severe Alzheimer's disease 5
- It can be used as monotherapy or in combination with cholinesterase inhibitors 6
- When combined with donepezil, memantine resulted in significantly better outcomes than placebo on measures of cognition, activities of daily living, and behavior 6
Common Side Effects
The most common adverse reactions (occurring in ≥5% of patients and at a rate greater than placebo) are:
- Dizziness
- Headache
- Confusion
- Constipation 1
Monitoring and Follow-up
Regular follow-up every 3-6 months is recommended to:
- Evaluate treatment effectiveness
- Assess for adverse effects
- Monitor disease progression
- Consider discontinuation if appropriate 4
Discontinuation Considerations
According to the Canadian Consensus Conference guidelines, memantine should be considered for discontinuation in patients taking it for >12 months if:
- There has been clinically meaningful worsening of dementia over the past 6 months
- No clinically meaningful benefit was observed during treatment
- The patient has progressed to severe or end-stage dementia
- Intolerable side effects develop (confusion, dizziness, falls)
- Medication adherence is poor 3
If discontinuation is warranted, dose reduction should occur gradually, with a 50% reduction every 4 weeks until reaching the initial starting dose, then complete discontinuation after 4 more weeks 3.