From the Guidelines
Memantine should be started at a dose of 5 mg once daily and gradually increased to minimize side effects, with a target maintenance dose of 20 mg daily. This recommendation is based on the evidence from high-quality studies, including a study published in the Annals of Internal Medicine 1, which evaluated the efficacy and safety of memantine in patients with Alzheimer's disease and vascular dementia. The study found that memantine resulted in statistically significant, but not clinically important, improvement on the ADAS-cog scale in cognition for individuals with mild to moderate vascular dementia and mild to moderate Alzheimer disease.
Initiation and Titration of Memantine
To minimize side effects, memantine should be started at a low dose and gradually increased. The recommended titration schedule is as follows:
- Week 1: 5 mg once daily
- Week 2: 5 mg twice daily
- Week 3: 10 mg in the morning and 5 mg in the evening
- Week 4: 10 mg twice daily (20 mg total daily dose)
Administration and Special Considerations
Memantine can be taken with or without food at the same times each day. For patients with moderate renal impairment, the target dose should be reduced to 10 mg daily, and for severe renal impairment, the dose should be limited to 5-10 mg daily 1. Common side effects of memantine include dizziness, headache, confusion, and constipation, which typically improve as the body adjusts to the medication.
Mechanism of Action and Clinical Benefits
Memantine works by regulating glutamate activity in the brain, specifically as an NMDA receptor antagonist, which helps improve cognitive function in conditions like Alzheimer's disease by preventing excessive glutamate stimulation that can damage nerve cells 1. The gradual titration schedule helps minimize side effects while allowing the body to adjust to the medication's effects. Overall, the evidence supports the use of memantine as a safe and effective treatment for Alzheimer's disease and vascular dementia, with benefits in cognitive function, behavior, and quality of life.
From the FDA Drug Label
For patients randomized to memantine hydrochloride, treatment was initiated at 5 mg once daily and increased weekly by 5 mg/day in divided doses to a dose of 20 mg/day (10 mg twice a day).
Starting Memantine:
- Initiate treatment at 5 mg once daily.
- Increase the dose weekly by 5 mg/day in divided doses.
- Target dose is 20 mg/day, which can be administered as 10 mg twice a day 2.
From the Research
Initiating Memantine Treatment
To start memantine, consider the following steps:
- Consult a healthcare professional for proper diagnosis and treatment of Alzheimer's disease or other conditions where memantine is indicated 3, 4.
- Discuss the potential benefits and risks of memantine treatment, including its efficacy in improving cognitive functions and behavioral disturbances 3, 4.
- Determine the appropriate dosage and administration schedule, typically starting with a low dose and gradually increasing as needed and tolerated 3, 5.
- Monitor for potential adverse events, such as somnolence, and adjust the treatment plan accordingly 3, 6.
Combination Therapy with Cholinesterase Inhibitors
Consider combination therapy with memantine and a cholinesterase inhibitor, such as donepezil, for moderate to severe Alzheimer's disease:
- This combination has been shown to produce significant benefits in cognition, function, behavior, and global outcome compared to monotherapy 4, 7.
- The complementary mechanisms of memantine and cholinesterase inhibitors may offer superior therapeutic benefits 7.
- Regularly monitor patients for potential side effects and adjust the treatment plan as needed 5.
Patient Monitoring and Follow-up
Regularly monitor patients initiating memantine treatment for: