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 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.


CONCLUSIONS
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).
Lovera
J F
JF
Neurology, Louisiana State University Health Sciences Center, New Orleans, LA 70003, USA. jlover@lsuhsc.edu
Frohman
E
E
Brown
T R
TR
Bandari
D
D
Nguyen
L
L
Yadav
V
V
Stuve
O
O
Karman
J
J
Bogardus
K
K
Heimburger
G
G
Cua
L
L
Remingon
G
G
Fowler
J
J
Monahan
T
T
Kilcup
S
S
Courtney
Y
Y
McAleenan
J
J
Butler
K
K
Wild
K
K
Whitham
R
R
Bourdette
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D003863:Depression / Q000523:psychology; D004311:Double-Blind Method; D005221:Fatigue / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000523:psychology; D009483:Neuropsychological Tests; D018579:Patient Selection; D011788:Quality of Life / Q000523:psychology; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D008559:Memantine