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Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial
J F Lovera1, E Frohman, T R Brown
1Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70003, USA. jlover@lsuhsc.edu
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 LDFR (placebo-memantine =-0.6 words, 95% CI -2.1, 0.8; p = 0.4) as well as on the other cognitive tests were not significant. Subjects on memantine had no serious adverse events (AEs) but had more fatigue and neurological AEs as well as, per family members' reports, less cognitive improvement and greater neuropsychiatric symptoms than subjects on placebo.
Conclusion:
Memantine 10 mg twice a day does not improve CP in subjects with MS, ages 18-65, without major depression, who have subjective cognitive complaints and perform worse than one SD below the mean on the PASAT or on the California Verbal Learning Test-II (total recall or delayed free recall).
Insights
Memantine did not improve cognitive performance in multiple sclerosis patients. The study found no significant cognitive benefits and noted increased fatigue and neurological side effects with memantine treatment.
Area of Science:
- Neuroscience
- Clinical Neurology
Background:
- Memantine is an NMDA antagonist approved for moderate to severe Alzheimer's disease.
- Multiple sclerosis (MS) can cause cognitive impairment (CI).
Purpose of the Study:
- To evaluate the efficacy of memantine in improving cognitive performance (CP) in individuals with MS and CI.
Main Methods:
- A double-blind, randomized, placebo-controlled trial (NCT00300716) was conducted.
- Participants received either 10 mg memantine twice daily or a placebo.
- Primary outcomes included changes in the Paced Auditory Serial Addition Test (PASAT) and California Verbal Learning Test-II (CVLT-II) Long Delay Free Recall (LDFR).
Main Results:
- No significant differences in CP were observed between the memantine and placebo groups on the PASAT or CVLT-II LDFR.
- Memantine was associated with increased fatigue and neurological adverse events.
- Caregiver reports indicated less cognitive improvement and more neuropsychiatric symptoms in the memantine group.
Conclusions:
- Memantine at 10 mg twice daily does not enhance cognitive function in adults (18-65) with MS experiencing subjective cognitive complaints and objective cognitive deficits.
- The study population excluded individuals with major depression.
- Further research may be needed to explore other therapeutic strategies for cognitive impairment in MS.
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