Memantine: Usage and Dosing for Alzheimer's Disease
Memantine is an NMDA receptor antagonist indicated for the treatment of moderate to severe Alzheimer's disease, with a recommended starting dose of 5 mg once daily that should be gradually titrated to a target dose of 20 mg/day. 1
Mechanism and Indications
- Memantine is a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that works by inhibiting excessive calcium influx caused by chronic overstimulation of the NMDA receptor 2
- It is specifically approved for treating moderate to severe dementia of the Alzheimer's type 1
- Unlike cholinesterase inhibitors, memantine represents a distinct pharmacological approach to treating Alzheimer's disease 3
Dosing Protocol
- The recommended starting dose is 5 mg (2.5 mL) once daily 1
- Dose should be increased in 5 mg increments with a minimum interval of one week between increases 1
- Titration 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) 1
- The clinically effective dose established in controlled trials is 20 mg/day 1
- Memantine can be taken with or without food 1
Special Populations
- For patients with severe renal impairment (creatinine clearance 5-29 mL/min), a reduced target dose of 5 mg twice daily is recommended 1
- Administer with caution to patients with severe hepatic impairment 1
Clinical Efficacy
- Memantine improves cognition and global assessment in patients with moderate to severe Alzheimer's disease, though the magnitude of effect may not reach clinical significance in all domains 4
- Studies demonstrate improvements in quality of life for patients with moderate to severe Alzheimer's disease 5
- Combination therapy with memantine plus a cholinesterase inhibitor (particularly donepezil) has shown superior outcomes compared to cholinesterase inhibitor therapy alone 3, 6
Adverse Effects and Tolerability
- Memantine is generally well tolerated with an adverse event profile similar to placebo 7
- Common adverse events include:
- Headache (5.6% vs 5.1% for placebo)
- Diarrhea (5.0% vs 3.9% for placebo)
- Dizziness (6.3% vs 5.7% for placebo)
- Agitation (7.5% vs 12.0% for placebo) 7
- Discontinuation rates due to adverse events are similar between memantine and placebo groups (8.9% vs 9.8%) 7
Duration of Treatment and Discontinuation
- Consider discontinuation if:
- Clinically meaningful worsening of dementia occurs over 6 months
- No clinical benefit is observed during treatment
- Patient progresses to severe or end-stage dementia 5
- When discontinuing, a gradual approach is recommended, reducing dose by 50% every 4 weeks until reaching the initial starting dose 5
Important Clinical Considerations
- Conditions that raise urine pH may decrease urinary elimination of memantine, potentially increasing plasma levels 1
- For patients with neuropsychiatric symptoms, continue memantine if there has been meaningful reduction in these symptoms, even with cognitive decline 5
- Extended-release formulations (28 mg once daily) have also shown efficacy and good tolerability 8