What is the recommended dosage and usage of memantine (Memantine) for treating Alzheimer's disease?

Memantine Dosing and Usage for Alzheimer's Disease

Memantine is indicated for moderate to severe Alzheimer's disease, with a target dose of 20 mg/day (10 mg twice daily for immediate-release or 28 mg once daily for extended-release formulations), titrated gradually over 4 weeks to minimize adverse effects. 1

Standard Dosing Protocol

Immediate-Release Formulation

The FDA-approved titration schedule follows a structured 4-week escalation 1:

• 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 is the target therapeutic dose 1

The minimum interval between dose increases is one week, and this 20 mg/day dose has been proven effective in controlled clinical trials 1.

Extended-Release Formulation

For the once-daily extended-release formulation, the target dose is 28 mg once daily, which provides higher total daily exposure and may offer convenience advantages for adherence 2, 3. This formulation demonstrated significant efficacy on cognition (SIB) and global status (CIBIC-Plus) in patients with moderate to severe AD taking cholinesterase inhibitors 2.

Clinical Indications and Patient Selection

Memantine is specifically approved for moderate to severe dementia of the Alzheimer's type 1. The evidence base is strongest for patients with:

• MMSE scores of 5-14 (moderate to severe disease) 4, 2
• Patients already on stable cholinesterase inhibitor therapy can safely add memantine with demonstrated additional benefit 4

The evidence for mild to moderate AD (higher MMSE scores) is equivocal, though meta-analyses suggest some benefit 5. The most robust data support use in moderate to severe disease 6, 7.

Administration Details

• Memantine can be taken with or without food 1
• If a single dose is missed, do not double the next dose 1
• If multiple doses are missed for several days, resume at lower doses and retitrate 1
• For oral solution: do not mix with other liquids; use the supplied dosing syringe and slowly squirt into the corner of the patient's mouth 1
• Extended-release capsules may be opened and sprinkled on applesauce for patients with swallowing difficulties 3

Special Population Adjustments

Severe Renal Impairment

Reduce target dose to 5 mg twice daily (10 mg/day total) in patients with creatinine clearance 5-29 mL/min 1. This is critical because memantine is primarily renally eliminated, and accumulation can occur with impaired kidney function.

Severe Hepatic Impairment

Administer with caution in severe hepatic impairment, though specific dose adjustments are not provided 1.

Conditions Raising Urine pH

Be cautious with conditions that alkalinize urine (renal tubular acidosis, severe UTIs, dietary changes), as these decrease urinary elimination and increase plasma memantine levels 1.

Expected Clinical Benefits

When used appropriately in moderate to severe AD, memantine demonstrates 6, 7:

• Cognition: Statistically significant improvements on the Severe Impairment Battery (SIB)
• Global function: Significant changes on CIBIC-Plus scale
• Activities of daily living: Improvements on ADCS-ADL scales 6
• Behavioral symptoms: May reduce neuropsychiatric symptoms and agitation 6
• Caregiver burden: Limited evidence shows improvements in caregiver burden and resource utilization 7

When combined with donepezil in moderate to severe AD, memantine showed superior outcomes versus donepezil alone on cognition (SIB: +0.9 vs -2.5, p<0.001), ADLs (ADCS-ADL19: -2.0 vs -3.4, p=0.03), and global status (CIBIC-Plus: 4.41 vs 4.66, p=0.03) 4.

Discontinuation Criteria

Consider stopping memantine if 7:

• Clinically meaningful worsening of dementia over the past 6 months without other contributing medical or environmental factors
• No clinically meaningful benefit observed at any time during treatment
• Severe or end-stage dementia with dependence in most basic ADLs, inability to respond to environment, or limited life expectancy

Exception: Continue memantine even with cognitive/functional decline if there has been clinically meaningful reduction in neuropsychiatric symptoms (psychosis, agitation, aggression) 7.

When discontinuing, use a gradual taper: reduce dose by 50% every 4 weeks until reaching the initial starting dose 7.

Safety Profile

Memantine is generally well tolerated 6, 1:

• Common adverse events: Headache (5.6%), diarrhea (5.0%), dizziness, nausea 1, 2
• Discontinuation rates: 7-12% due to adverse events (similar to placebo rates of 7-13%) 7, 1
• Agitation: Memantine may actually have a protective effect against agitation 6
• Serious adverse events: No significant differences versus placebo 6

The combination of memantine with cholinesterase inhibitors is safe and well tolerated, with discontinuation rates of 7.4% versus 12.4% for placebo 4.

Common Pitfalls to Avoid

• Titrating too quickly: Always maintain at least one week between dose increases to minimize adverse effects 1
• Using in mild AD without evidence: The strongest evidence supports moderate to severe disease; use in mild AD is not well established 5
• Ignoring renal function: Failure to dose-adjust in severe renal impairment can lead to drug accumulation 1
• Premature discontinuation: If neuropsychiatric symptoms improve, continue memantine even if cognition declines 7