Beth A Leeman-Markowski1, Kimford J Meador2, Lauren R Moo3, Andrew J Cole4, Daniel B Hoch4, Eduardo Garcia5, Steven C Schachter6. 1. Research Service, VA New York Harbor Healthcare System, New York, NY, USA; Department of Neurology, New York University Langone Medical Center, New York, NY, USA. Electronic address: beth.leeman-markowski@nyumc.org. 2. Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Palo Alto, CA, USA. 3. Geriatric Research Education and Clinical Center, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 4. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. 5. Tufts University School of Medicine, Boston, MA, USA; Newton-Wellesley Neurology Associates, PC, Newton Lower Falls, MA, USA. 6. Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.
Abstract
OBJECTIVE:Excitotoxic injury involving N-methyl-d-aspartate (NMDA) receptor hyperactivity contributes to epilepsy-related memory dysfunction (ERMD). Current treatment strategies for ERMD have limited efficacy and fail to target the underlying pathophysiology. The present pilot study evaluated the efficacy of memantine, an NMDA receptor antagonist, for the treatment of ERMD in adults with focal-onset seizures. METHODS: Subjects underwent cognitive testing at baseline, after a 13-week randomized, parallel-group, double-blinded phase (of memantine titrated to 10 mg bid or placebo), and following a 13-week open-label extension phase (of memantine titrated to 10 mg bid). The selective reminding test (SRT) continuous long-term retrieval (CLTR) score and 7/24 Spatial Recall Test learning score served as the primary outcome measures. Secondary measures included tests of attention span, fluency, visual construction, and response inhibition, as well as assessments of quality of life, depression, sleepiness, and side effects. RESULTS:Seventeen subjects contributed data to the blinded phase (n = 8 memantine, n = 9 placebo). No significant differences were seen between groups on the primary or secondary outcome measures. Pooled data at the end of the open-label phase from 10 subjects (initially randomized to memantinen = 3 or placebon = 7) demonstrated statistically significant improvement from baseline in CLTR score, memory-related quality of life, spatial span, and response inhibition. No significant changes were evident in depression, sleepiness, side effects, or seizure frequency throughout the trial. SIGNIFICANCE: Results demonstrated no significant effect of memantine on cognition when assessed at the end of the blinded period. Pooled data at the end of the open-label phase showed significant improvement over baseline performance in measures of verbal memory, frontal-executive function, and memory-related quality of life. These improvements, however, may be due to practice effects and should be interpreted cautiously. Findings suggest a favorable safety profile of memantine in the setting of epilepsy. Published by Elsevier Inc.
RCT Entities:
OBJECTIVE:Excitotoxic injury involving N-methyl-d-aspartate (NMDA) receptor hyperactivity contributes to epilepsy-related memory dysfunction (ERMD). Current treatment strategies for ERMD have limited efficacy and fail to target the underlying pathophysiology. The present pilot study evaluated the efficacy of memantine, an NMDA receptor antagonist, for the treatment of ERMD in adults with focal-onset seizures. METHODS: Subjects underwent cognitive testing at baseline, after a 13-week randomized, parallel-group, double-blinded phase (of memantine titrated to 10 mg bid or placebo), and following a 13-week open-label extension phase (of memantine titrated to 10 mg bid). The selective reminding test (SRT) continuous long-term retrieval (CLTR) score and 7/24 Spatial Recall Test learning score served as the primary outcome measures. Secondary measures included tests of attention span, fluency, visual construction, and response inhibition, as well as assessments of quality of life, depression, sleepiness, and side effects. RESULTS: Seventeen subjects contributed data to the blinded phase (n = 8 memantine, n = 9 placebo). No significant differences were seen between groups on the primary or secondary outcome measures. Pooled data at the end of the open-label phase from 10 subjects (initially randomized to memantine n = 3 or placebo n = 7) demonstrated statistically significant improvement from baseline in CLTR score, memory-related quality of life, spatial span, and response inhibition. No significant changes were evident in depression, sleepiness, side effects, or seizure frequency throughout the trial. SIGNIFICANCE: Results demonstrated no significant effect of memantine on cognition when assessed at the end of the blinded period. Pooled data at the end of the open-label phase showed significant improvement over baseline performance in measures of verbal memory, frontal-executive function, and memory-related quality of life. These improvements, however, may be due to practice effects and should be interpreted cautiously. Findings suggest a favorable safety profile of memantine in the setting of epilepsy. Published by Elsevier Inc.
Authors: Pierre N Tariot; Martin R Farlow; George T Grossberg; Stephen M Graham; Scott McDonald; Ivan Gergel Journal: JAMA Date: 2004-01-21 Impact factor: 56.272
Authors: Joanne Taylor; Ruwanthi Kolamunnage-Dona; Anthony G Marson; Philip E M Smith; Albert P Aldenkamp; Gus A Baker Journal: Epilepsia Date: 2009-07-02 Impact factor: 5.864
Authors: Christoph Helmstaedter; Martin Kurthen; Silke Lux; Markus Reuber; Christian Erich Elger Journal: Ann Neurol Date: 2003-10 Impact factor: 10.422