Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial

Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimer’s disease.Objective: Determine whether memantine improves cognitive performance (CP) among subjects with multiple sclerosis (MS) and cognitive impairment (CI).Methods: This double-blind, randomized, placebo-controlled trial (Clinicaltrials.gov NCT00300716) compared memantine 10 mg twice a day (4 week titration followed by 12 weeks on the highest tolerated dose) with placebo. The primary outcome was the change from baseline to exit on the Paced Auditory Serial Addition Test (PASAT) and the California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR). Secondary outcomes included additional neuropsychological tests; self-report measures of quality of life, fatigue, and depression; and family/caregiver reports of subjects’ CI and neuropsychiatric symptoms.Results: The differences between the groups on the change on the PASAT (placebo—memantine = 0.0 correct responses, 95% CI 3.4, 3.4; p = 0.9) and on CVLT-II...