Recommended Treatment Regimen for Memantine in Moderate to Severe Alzheimer's Disease
Memantine at a dosage of 20 mg/day is the recommended treatment for moderate to severe Alzheimer's disease, with a gradual titration schedule starting at 5 mg/day and increasing by 5 mg increments weekly until reaching the target dose. 1
Dosing Protocol
- Start with 5 mg (2.5 mL) once daily 1
- Increase dose in 5 mg increments with a minimum interval of one week between dose increases 1
- Titration schedule:
- Week 1: 5 mg (2.5 mL) once daily
- Week 2: 10 mg/day (2.5 mL twice daily)
- Week 3: 15 mg/day (2.5 mL and 5 mL as separate doses)
- Week 4: 20 mg/day (5 mL twice daily) - this is the target effective dose 1
- Memantine can be taken with or without food 1
- If doses are missed for several days, dosing should be resumed at lower doses and retitrated as described above 1
Special Populations
- For patients with severe renal impairment (creatinine clearance of 5-29 mL/min), the recommended target dose is 5 mg twice daily (10 mg/day total) 1
- Administer with caution to patients with severe hepatic impairment 1
- Conditions that raise urine pH may decrease urinary elimination of memantine, resulting in increased plasma levels 1
Clinical Efficacy
- Memantine shows statistically significant improvement in cognition scores for moderate to severe Alzheimer's disease as measured by the Severe Impairment Battery (SIB) 2
- Studies demonstrate statistically significant changes on the CIBIC-plus scale (global assessment) for patients with moderate to severe Alzheimer's disease 2
- Limited evidence shows improvement in quality of life, caregiver burden, and resource utilization 2
- Combination therapy with cholinesterase inhibitors (particularly donepezil) has shown additional benefits:
Adverse Effects and Monitoring
- Common adverse events include nausea, dizziness, diarrhea, and agitation 2, 1
- Withdrawal rates due to adverse effects range from 9-12% in treatment groups (compared to 7-13% in placebo groups) 2
- No individual adverse reaction was associated with treatment discontinuation in ≥1% of memantine-treated patients at a rate greater than placebo 1
Duration of Treatment and Discontinuation
Consider discontinuation if:
- There has been clinically meaningful worsening of dementia over the past 6 months without other medical conditions or environmental factors contributing to the decline 2
- No clinically meaningful benefit observed at any time during treatment 2
- The individual has severe or end-stage dementia (dependence in most basic activities of daily living, inability to respond to environment, or limited life expectancy) 2
- Development of intolerable side effects (confusion, dizziness, falls) 2
- Poor medication adherence that precludes safe ongoing use 2
When discontinuing memantine, a gradual approach is recommended:
- Reduce dose by 50% every 4 weeks until reaching the initial starting dose 2
- After 4 weeks on the starting dose, the medication can be discontinued 2
- Reinitiate treatment if the individual shows clinically meaningful worsening of cognition, functioning, neuropsychiatric symptoms, or global assessment that appears related to cessation of therapy 2
Important Clinical Considerations
- Memantine is FDA-approved specifically for moderate to severe Alzheimer's disease 1
- While some studies have evaluated memantine in mild Alzheimer's disease, the evidence is equivocal 4
- Memantine should be discontinued for indications other than Alzheimer's disease, Parkinson's disease dementia, dementia with Lewy bodies, or vascular dementia 2
- For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms, even if there is evidence of cognitive and functional decline 2