Memantine Dosing and Treatment Guidelines for Moderate to Severe Alzheimer's Disease
The recommended dosing for memantine in moderate to severe Alzheimer's disease is to start at 5 mg once daily and titrate weekly in 5 mg increments to a target maintenance dose of 20 mg/day (10 mg twice daily). 1
Dosing Schedule and Administration
- Initial dose is 5 mg (2.5 mL) once daily 1
- Increase dose in 5 mg increments to:
- 10 mg/day (5 mg twice daily)
- 15 mg/day (5 mg and 2.5 mg as separate doses)
- 20 mg/day (10 mg twice daily) 1
- Minimum interval between dose increases should be one week 1
- Memantine can be taken with or without food 1
- For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the recommended target dose is 5 mg twice daily 1
- Administer with caution in 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, 4
- 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
- Benefits have been shown in quality of life, with less agitation reported in treatment groups compared to placebo 5, 4
- Improvements in activities of daily living (ADLs) have been demonstrated in three out of four studies evaluating this outcome 2
Combination Therapy
- Memantine can be used as monotherapy or in combination with cholinesterase inhibitors 3, 5, 4
- Combination therapy with memantine plus a cholinesterase inhibitor has shown superior outcomes compared to cholinesterase inhibitor therapy alone 3, 4
- A randomized controlled trial demonstrated that adding memantine to stable donepezil treatment resulted in significantly better outcomes in cognition, activities of daily living, global outcome, and behavior compared to placebo 6
Adverse Effects and Monitoring
- Common adverse events include dizziness (6.3% vs 5.7% placebo), headache (5.2% vs 3.7% placebo), confusion, and constipation 1, 7
- Nausea, diarrhea, and agitation may also occur, though agitation was less frequently reported in treatment groups than in placebo groups in most studies 2, 4
- Withdrawal rates due to adverse effects range from 7.4% to 12% in treatment groups (compared to 7-13% in placebo groups) 4, 6, 7
- Conditions that raise urine pH may decrease the urinary elimination of memantine, resulting in increased plasma levels 1
Treatment Duration and Discontinuation
- Consider discontinuation if there has been clinically meaningful worsening of dementia over 6 months without other contributing factors 5, 4
- Consider discontinuation if no clinical benefit is observed during treatment 5, 4
- Consider discontinuation if the patient progresses to severe or end-stage dementia with dependence in most basic activities of daily living 5, 4
- When discontinuing memantine, a gradual approach is recommended, reducing dose by 50% every 4 weeks until reaching the initial starting dose 3, 5, 4
Special 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 5, 4
- Memantine is generally well tolerated with an adverse event profile similar to placebo in both short-term and long-term studies (up to 2 years) 7
- While memantine is primarily indicated for moderate to severe Alzheimer's disease, some studies have shown benefits in mild to moderate disease, particularly in language and memory domains 8, 9