Starting Dose of Memantine for Elderly Patients with Advancing Dementia
The recommended starting dose of memantine for an elderly patient with advancing dementia is 5 mg once daily, with gradual titration in 5 mg increments at weekly intervals to a target maintenance dose of 20 mg/day (10 mg twice daily). 1
Initial Dosing Protocol
Start with 5 mg once daily and increase in 5 mg increments following this specific titration schedule: 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)
The minimum interval between dose increases must be one week to allow for tolerance assessment and minimize adverse effects 1
The target maintenance dose of 20 mg/day (10 mg twice daily) is the dosage proven effective in controlled clinical trials for moderate to severe Alzheimer's disease 2, 3, 1
Critical Dose Adjustments for Elderly Patients
For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the target dose should be reduced to 5 mg twice daily (10 mg total daily) rather than the standard 20 mg/day 1, 3
This renal adjustment is essential because the area under the curve increases by 115% in severe renal impairment, and the lower dose achieves comparable steady-state concentrations to normal dosing in patients with normal renal function 3
For patients with severe hepatic impairment, memantine should be administered with caution, though specific dose adjustments are not definitively established 1
Important Clinical Considerations for Elderly Patients
Memantine can be taken with or without food, which provides flexibility for elderly patients with varying eating schedules 1
If a patient misses several days of treatment, do not resume at the previous dose—restart at lower doses and retitrate following the weekly increment schedule 1
The oral solution formulation (2 mg/mL) may be preferable for elderly patients with swallowing difficulties, administered using the supplied dosing syringe slowly squirted into the corner of the mouth 1
Efficacy Evidence Supporting This Dosing
The 20 mg/day dose demonstrates statistically significant improvements in cognition (measured by Severe Impairment Battery), global assessment (CIBIC-plus scale), and quality of life measures in moderate to severe Alzheimer's disease 2, 4, 3
Benefits are seen in patients with moderate-to-severe AD whether or not they are concurrently taking cholinesterase inhibitors 5, 6
High-certainty evidence shows small but consistent clinical benefits across cognitive function (3.11 SIB points), activities of daily living (1.09 ADL19 points), and behavior/mood (1.84 NPI points) compared to placebo 6
Safety Profile at Standard Dosing
Discontinuation rates due to adverse effects are 9-12% with memantine versus 7-13% with placebo, indicating generally good tolerability 2, 3
The most common adverse effects in elderly patients include dizziness, headache, confusion, and constipation 1, 3
There is moderate-certainty evidence of increased dizziness risk (6.1% versus 3.9% with placebo) and headache (5.5% versus 4.3%), but no increased risk of falls 6
Critical Pitfall to Avoid
Do not use memantine for mild dementia or mild cognitive impairment in elderly patients—the evidence shows no benefit in mild AD (MMSE 20-23), and guidelines recommend deprescribing memantine for mild cognitive impairment 2, 6
The clinical benefit is specifically demonstrated for moderate to severe dementia, making appropriate severity assessment essential before initiating therapy 4, 1, 6