Should the dose of memantine (Namenda) be increased in a 71-year-old patient with impaired memory who initially responded to 5 milligrams twice daily (BID) but is no longer experiencing significant benefit?

From the Guidelines

Increasing the memantine dose to 10 mg twice daily may be considered for a 71-year-old patient who initially responded to 5 mg twice daily but is now experiencing diminished benefits, as the standard therapeutic dose is typically 10 mg twice daily, reached through gradual titration 1. When considering a dose increase, it's essential to evaluate other factors that might affect cognition, including medication interactions, sleep quality, and any new medical conditions. The patient should be monitored for side effects and cognitive response after the dose adjustment. Some key points to consider when making this decision include:

• The patient's initial response to memantine suggests that it was effective in improving their memory, but the diminishing benefits may indicate a need for a higher dose.
• The guidelines recommend considering discontinuation of memantine if there has been a clinically meaningful worsening of dementia, no clinically meaningful benefit was observed, or the individual has severe or end-stage dementia 1.
• However, since the patient is still experiencing some benefits from the medication, increasing the dose may be a more appropriate option than discontinuing it.
• It's crucial to follow a gradual titration schedule to minimize potential side effects, such as dizziness, headache, or confusion, and to monitor the patient's response to the increased dose.
• If increasing to the standard dose doesn't provide benefit, or if side effects occur, a comprehensive reevaluation of the treatment approach would be warranted, considering the patient's preferences, prior expressed wishes, and collaboration with family or substitute decision makers 1.

From the FDA Drug Label

The dose should be increased in 5 mg increments to 10 mg/day (2.5 mL twice daily), 15 mg/day (2. 5 mL and 5 mL as separate doses), and 20 mg/day (5 mL twice daily). The minimum recommended interval between dose increases is one week. The dosage shown to be effective in controlled clinical trials is 20 mg/day (5 mL twice daily).

The patient is currently taking memantine 5 mg twice daily. Dose increase is possible, and the recommended dose can be increased to 10 mg/day (5 mg twice daily) with a minimum interval of one week between dose increases. However, it is essential to monitor the patient's response and adjust the dose accordingly. The maximum effective dose shown in clinical trials is 20 mg/day.

• The patient's current dose is 5 mg twice daily, which is 10 mg/day.
• A dose increase to 15 mg/day or 20 mg/day may be considered, but it should be done with caution and under close monitoring.
• The patient's age and potential renal impairment should be taken into account when adjusting the dose, as the target dose for patients with severe renal impairment is 5 mg twice daily 2.

From the Research

Dose Increase Considerations for Memantine

• The current dose of memantine is 5 mg twice a day (BID), and the patient is 71 years old 3.
• Studies have shown that memantine is effective in moderate-to-severe Alzheimer's disease, with a licensed dose of 20 mg/day or 28 mg extended release 3.
• Increasing the dose of memantine may be considered, but it is essential to weigh the potential benefits against the risks of adverse events.
• A study on the pharmacokinetics of memantine found that the maximum plasma concentration of memantine after multiple-dose administration was greater than that after a single-dose administration, suggesting memantine accumulation with multiple-dose administration of 5 mg 4.

Efficacy of Memantine in Alzheimer's Disease

• Memantine has been shown to have a small clinical benefit in people with moderate-to-severe Alzheimer's disease, with improvements in cognitive function, activities of daily living, and behavioral disturbances 3, 5, 6.
• Combination therapy with cholinesterase inhibitors and memantine has been found to be beneficial for the treatment of moderate-to-severe Alzheimer's disease, with significant effects on behavioral disturbance scores, activity of daily living scores, and global assessment scores 5, 6.

Safety and Tolerability

• Memantine has been found to be generally well-tolerated, with a similar discontinuation rate compared to placebo 3, 6.
• Common adverse events associated with memantine include dizziness, headache, and confusion 3.
• A study on the safety and tolerability of memantine found that the maximum plasma concentration of memantine after multiple-dose administration was greater than that after a single-dose administration, suggesting memantine accumulation with multiple-dose administration of 5 mg 4.