Can Namenda (memantine) be used to treat memory loss in a patient with multiple sclerosis (MS)?

Memantine (Namenda) Should Not Be Used for Memory Loss in Multiple Sclerosis

Memantine is not recommended for treating memory loss in patients with multiple sclerosis, as multiple high-quality randomized controlled trials have demonstrated no cognitive benefit and significant risk of neurological worsening specific to the MS population. 1, 2, 3

Evidence Against Use in MS

Lack of Efficacy

• No improvement in memory performance was demonstrated in MS patients treated with memantine across multiple validated cognitive measures including the Paced Auditory Serial Addition Test (PASAT) and California Verbal Learning Test-II (CVLT-II). 2, 3
• A 52-week randomized controlled trial in relapsing-remitting MS patients showed no difference in PASAT scores between memantine (20 mg/day) and placebo groups (adjusted mean score difference: -0.40,95% CI: -5.5 to +4.7, p=0.88). 1
• Secondary cognitive outcomes including short-term memory, attention scores, and quality of life measures showed no significant differences. 1, 2

Significant Safety Concerns Specific to MS

• Memantine causes reversible neurological worsening in MS patients that does not occur in Alzheimer's disease populations. 4
• A pilot trial was halted early after 7 of 9 patients (78%) on memantine developed worsening neurological symptoms including blurred vision, severe fatigue, increased muscle weakness, walking difficulties, and unstable gait. 4
• Neurological and psychiatric adverse events were significantly higher in MS patients taking memantine compared to placebo, exceeding rates reported in the product literature for Alzheimer's disease. 1
• Symptoms resolved within days after stopping medication, but the risk of temporary disability is clinically significant. 4

Tolerability Issues

• MS patients on memantine reported more fatigue and neurological adverse events than those on placebo. 2
• Family members reported less cognitive improvement and greater neuropsychiatric symptoms in memantine-treated patients compared to placebo. 2
• The tolerability profile was significantly worse than expected based on Alzheimer's disease data. 1

Why Memantine Works Differently in MS vs. Alzheimer's Disease

While memantine is FDA-approved for moderate to severe Alzheimer's disease and shows modest benefits in vascular dementia 5, 6, the pathophysiology of cognitive impairment differs fundamentally between these conditions and MS:

• In Alzheimer's disease, memantine improves ADAS-cog scores by 1-3 points and shows benefits in global cognitive function. 5
• In vascular cognitive impairment, memantine demonstrates significant improvement on cognitive measures and is recommended in current guidelines. 5
• In MS, the mechanism of cognitive impairment involves demyelination and axonal loss rather than the glutamate-mediated excitotoxicity that memantine targets in neurodegenerative dementias. 3

Clinical Bottom Line

Do not prescribe memantine for MS-related memory complaints. The evidence is clear and consistent across multiple trials that it provides no benefit and carries unique risks in this population. 1, 2, 4, 3

Alternative Approaches

• Focus on disease-modifying therapies to prevent further MS-related neurological damage. 3
• Consider cognitive rehabilitation and compensatory strategies rather than pharmacological symptomatic treatment. 3
• Screen for and treat comorbid conditions that may worsen cognition (depression, fatigue, sleep disorders). 2