Memantine Treatment for Moderate to Severe Alzheimer's Disease
For patients with moderate to severe Alzheimer's disease, memantine (Namenda) is recommended at a starting dose of 5 mg once daily, with weekly 5 mg increments to reach the target dose of 20 mg/day (10 mg twice daily), which has been shown to improve cognition, global function, and quality of life. 1
Dosing Protocol
- Initial dose: 5 mg (2.5 mL) once daily 1
- Titration: Increase in 5 mg increments at weekly intervals 1
- Week 2: 10 mg/day (5 mg twice daily) 1
- Week 3: 15 mg/day (5 mg and 10 mg as separate doses) 1
- Week 4 and beyond: 20 mg/day (10 mg twice daily) - maintenance dose 1
Administration Guidelines
- Can be taken with or without food 1
- If a dose is missed, patient should not double up; take the next dose as scheduled 1
- If treatment is interrupted for several days, restart at lower dose and retitrate 1
- For oral solution: use provided dosing syringe, slowly squirt into corner of patient's mouth 1
Special Populations
- Renal impairment: For severe renal impairment (creatinine clearance 5-29 mL/min), reduce to 5 mg twice daily 1
- Hepatic impairment: Administer with caution to patients with severe hepatic impairment 1
Clinical Efficacy
- Memantine improves cognition and global assessment in moderate to severe Alzheimer's disease, though the magnitude of effect may not reach clinical significance in all domains 2, 3
- Studies demonstrate statistically significant improvements on the Severe Impairment Battery (SIB) and CIBIC-plus scale for patients with moderate to severe Alzheimer's disease 4, 5
- Memantine shows benefits in quality of life, with less agitation reported in treatment groups compared to placebo 2, 4
Combination Therapy
- Memantine can be used as monotherapy or in combination with cholinesterase inhibitors 3, 5
- Combination therapy with memantine plus a cholinesterase inhibitor (particularly donepezil) has shown superior outcomes compared to cholinesterase inhibitor therapy alone 4, 5
- In patients receiving stable doses of donepezil, adding memantine resulted in significantly better outcomes on measures of cognition, activities of daily living, global outcome, and behavior 5
Adverse Effects
- Most common adverse reactions (≥5% and greater than placebo): dizziness, headache, confusion, and constipation 1
- Withdrawal rates due to adverse effects range from 9-12% in treatment groups (compared to 7-13% in placebo groups) 4
- Conditions that raise urine pH may decrease urinary elimination of memantine, resulting in increased plasma levels 1
Extended-Release Option
- Memantine extended-release (28 mg once daily) is available as an alternative to twice-daily dosing 6
- Potential advantages include more convenient dosage regimen and lower pill burden that may improve adherence 6
- Extended-release capsules can be opened and contents sprinkled on applesauce for patients with difficulty swallowing 6
Treatment Duration and Discontinuation
- Consider discontinuation if clinically meaningful worsening of dementia occurs over 6 months without other contributing factors 4
- Consider discontinuation if no clinical benefit is observed during treatment 4
- Consider discontinuation if the patient progresses to severe or end-stage dementia with dependence in most basic activities of daily living 4
- When discontinuing, use a gradual approach, reducing dose by 50% every 4 weeks until reaching the initial starting dose 3, 4
Important Clinical Considerations
- For patients with neuropsychiatric symptoms (psychosis, agitation, aggression), continue memantine if there has been a clinically meaningful reduction in these symptoms, even with cognitive and functional decline 4
- Memantine is currently the only approved option for the treatment of moderate to severe Alzheimer's disease 7