Memantine for cognitive impairment in multiple sclerosis

A randomized placebo-controlled trial

J. F. Lovera, E. Frohman, T. R. Brown, D. Bandari, L. Nguyen, Vijayshree Yadav, O. Stuve, J. Karman, K. Bogardus, G. Heimburger, L. Cua, G. Remingon, J. Fowler, T. Monahan, S. Kilcup, Y. Courtney, J. McAleenan, K. Butler, Katherine Wild, Ruth Whitham & 1 others Dennis Bourdette

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimers 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).

Original languageEnglish (US)
Pages (from-to)715-723
Number of pages9
JournalMultiple Sclerosis
Volume16
Issue number6
DOIs
StatePublished - 2010

Fingerprint

Memantine
Multiple Sclerosis
Randomized Controlled Trials
Placebos
Verbal Learning
Fatigue
Depression
Neuropsychological Tests
N-Methylaspartate
Cognitive Dysfunction
Double-Blind Method
Self Report
Caregivers
Alzheimer Disease
Quality of Life

Keywords

  • Attention
  • Cognition disorders
  • Memantine
  • Memory
  • Multiple sclerosis
  • Neuropsychological tests
  • Placebo
  • Randomized controlled trial

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Memantine for cognitive impairment in multiple sclerosis : A randomized placebo-controlled trial. / Lovera, J. F.; Frohman, E.; Brown, T. R.; Bandari, D.; Nguyen, L.; Yadav, Vijayshree; Stuve, O.; Karman, J.; Bogardus, K.; Heimburger, G.; Cua, L.; Remingon, G.; Fowler, J.; Monahan, T.; Kilcup, S.; Courtney, Y.; McAleenan, J.; Butler, K.; Wild, Katherine; Whitham, Ruth; Bourdette, Dennis.

In: Multiple Sclerosis, Vol. 16, No. 6, 2010, p. 715-723.

Research output: Contribution to journalArticle

Lovera, JF, Frohman, E, Brown, TR, Bandari, D, Nguyen, L, Yadav, V, Stuve, O, Karman, J, Bogardus, K, Heimburger, G, Cua, L, Remingon, G, Fowler, J, Monahan, T, Kilcup, S, Courtney, Y, McAleenan, J, Butler, K, Wild, K, Whitham, R & Bourdette, D 2010, 'Memantine for cognitive impairment in multiple sclerosis: A randomized placebo-controlled trial', Multiple Sclerosis, vol. 16, no. 6, pp. 715-723. https://doi.org/10.1177/1352458510367662
Lovera, J. F. ; Frohman, E. ; Brown, T. R. ; Bandari, D. ; Nguyen, L. ; Yadav, Vijayshree ; Stuve, O. ; Karman, J. ; Bogardus, K. ; Heimburger, G. ; Cua, L. ; Remingon, G. ; Fowler, J. ; Monahan, T. ; Kilcup, S. ; Courtney, Y. ; McAleenan, J. ; Butler, K. ; Wild, Katherine ; Whitham, Ruth ; Bourdette, Dennis. / Memantine for cognitive impairment in multiple sclerosis : A randomized placebo-controlled trial. In: Multiple Sclerosis. 2010 ; Vol. 16, No. 6. pp. 715-723.
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abstract = "Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimers 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).",
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AU - Bandari, D.

AU - Nguyen, L.

AU - Yadav, Vijayshree

AU - Stuve, O.

AU - Karman, J.

AU - Bogardus, K.

AU - Heimburger, G.

AU - Cua, L.

AU - Remingon, G.

AU - Fowler, J.

AU - Monahan, T.

AU - Kilcup, S.

AU - Courtney, Y.

AU - McAleenan, J.

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AU - Wild, Katherine

AU - Whitham, Ruth

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N2 - Background: Memantine, an NMDA antagonist, is effective for moderate to severe Alzheimers 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).

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