Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials

Abstract

Background: Multiple sclerosis (MS), a disabling demyelinating disease of the central nervous system, is associated with cognitive impairment, spasticity, and fatigue. There are still no established guidelines on the management of MS-related sequela. Memantine has the potential to reduce glutamate toxicity, thereby reducing consequent cognitive impairment, spasticity, and fatigue.Objectives: This study aims to determine the efficacy and safety of memantine in preventing cognitive impairment, reducing spasticity and fatigue, and controlling disability in MS patients through a review of relevant randomized trials.Methods: MEDLINE, CENTRAL, Scopus, Embase, LILACS, ClinicalTrials.gov, and HERDIN were searched from inception to May 2020 for relevant trials.Results: The search yielded 203 articles; four studies were included in the analysis. Pooled evidence shows that memantine compared with placebo does not significantly improve PASAT, ASS, MFIS, and EDSS scores of patients with MS. Memantine is associated with mild adverse drug events such as dizziness, fatigue, and anxiety.Conclusion: There is not enough evidence to support the efficacy of memantine in preventing cognitive decline, controlling spasticity, reducing fatigue, and preventing disability. Future researches should consider the different MS subtypes, effect of co-administration of disease-modifying therapies, longer duration of administration, and more sensitive outcome measures to evaluate the potential benefit of memantine in MS.

Pathophysiological Ionotropic Glutamate Signalling in Neuroinflammatory Disease as a Therapeutic Target

“…However, in AD, although improvement in patients was seen in terms of cognition and behaviour, the efficacy outcomes reported were modest ( Matsunaga et al, 2015 ; Kishi et al, 2017 ), with unclear effects on brain volume ( Yang et al, 2013 ). Similarly in MS, trials using memantine have been performed, but no significant effects were seen on either cognitive impairment or disability ( Peyro Saint Paul et al, 2016 ; Turalde et al, 2020 ). Therefore, the search for novel neuroprotective therapeutic targets and strategies continues.…”

Sub-clinical glutamate receptor antagonist combinations prevent progressive demyelination

“…Monotherapy with NMDA or AMPA antagonists is protective in EAE models of MS, but in general only at high concentrations 3,[28][29][30][31] . For example, the protection afforded by memantine requires a dose of 60 mg/kg/day, while a dose of 10-20 mg/kg/day in rodents correlates with the clinical guidelines for memantine in humans 32 , a dose that has no benefit in clinical trials of MS patients 33 . The memantine/perampanel CLD-GA paradigm that is effective against CPZ-induced white matter injury was based on doses an order of magnitude below the clinical treatment range for these drugs and is an attractive alternative to full-dose co-administration such as that tested in stage II clinical trials for glioblastoma (eg., 34 ).…”

A Narrative Review on Axonal Neuroprotection in Multiple Sclerosis

“…To date, clinical trials have failed to demonstrate any significant effect of memantine on patients with MS whatever the parameter investigated: fatigue, cognitive performance, or spasticity [ 247 – 251 ] (Table 6 ). Worse still, adverse events have been reported in several studies.…”