What is the recommended dosage and treatment protocol for Namenda (memantine) in patients with moderate to severe Alzheimer's disease?

Memantine (Namenda) Dosage and Treatment Protocol for Moderate to Severe Alzheimer's Disease

The recommended dosage protocol for memantine (Namenda) in moderate to severe Alzheimer's disease is to start at 5 mg once daily and titrate weekly in 5 mg increments to a target maintenance dose of 20 mg/day (given as 10 mg twice daily). 1

Dosing Titration Schedule

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

The minimum recommended interval between dose increases is one week, and the dosage shown to be effective in controlled clinical trials is 20 mg/day (10 mg twice daily). 1

Administration Guidelines

• Memantine can be taken with or without food
• If a dose is missed, the patient should not double up on the next dose
• If treatment is interrupted for several days, dosing should be resumed at lower doses and retitrated
• For oral solution formulation, do not mix with any other liquid and use the supplied dosing device 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
• Hepatic impairment: Administer with caution to patients with severe hepatic impairment 1

Extended-Release Option

An extended-release formulation (Namenda XR) is available as a 28 mg once-daily capsule, which may improve medication adherence through reduced pill burden and more convenient dosing. The capsules can be opened and contents sprinkled on applesauce for patients with swallowing difficulties. 2

Efficacy and Combination Therapy

Memantine has shown statistically significant, though modest, improvements in:

• Cognition
• Global function
• Quality of life
• Caregiver burden and resource utilization 3

Evidence strongly supports using memantine in combination with cholinesterase inhibitors (particularly donepezil) for moderate to severe Alzheimer's disease. The combination therapy has demonstrated superior outcomes in cognition, function, behavior, and global assessment compared to cholinesterase inhibitor monotherapy. 4

Duration of Therapy

• A beneficial effect, if any, is generally observed within 3 months based on clinical trials
• No clear evidence exists to determine the optimal duration of therapy
• Treatment should be discontinued when slowing decline is no longer a goal 3

Common Adverse Effects

Most common adverse reactions (≥5% and greater than placebo) include:

• Dizziness
• Headache
• Confusion
• Constipation 1

Withdrawal rates due to adverse effects range from 9-12% (similar to placebo at 7-13%). 3

Important Clinical Considerations

• Memantine is FDA-approved specifically for moderate to severe Alzheimer's disease 1
• Conditions that raise urine pH may decrease memantine elimination, resulting in increased plasma levels 1
• The choice between memantine and other agents should consider tolerability, adverse effect profile, ease of use, and medication cost 3
• Regular reassessment of cognitive, functional, and behavioral symptoms is necessary to monitor disease progression and treatment response

Remember that while memantine can provide symptomatic improvement and slow clinical decline, it does not cure the underlying disease process. Treatment decisions should prioritize quality of life and functional outcomes for patients with moderate to severe Alzheimer's disease.