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Research Letter
November 2015

Association Between Glutamate Blockade and Fatigue in Patients With Multiple Sclerosis

Author Affiliations
  • 1Department of Neurology, University of California–San Francisco
JAMA Neurol. 2015;72(11):1374-1375. doi:10.1001/jamaneurol.2015.2332

Excitotoxity, primarily mediated by excessive glutamate release, is one of the main proposed mechanisms for neurodegeneration in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis.1 However, a few clinical trials of medications with glutamate-blocking properties have not yet shown beneficial effects in patients with MS.

Fatigue is one of the most frequently reported MS symptoms and the underlying mechanisms of this potentially debilitating symptom are not well understood.2 Here, we report the effects of riluzole, a medication with glutamate-blocking properties, on fatigue in a randomized clinical trial in patients with early MS.

This is an analysis of a randomized, double-blind, placebo-controlled trial assessing the possible neuroprotective effects of riluzole in combination with intramuscular interferon β-1a that was conducted at 2 centers. The methods, including inclusion and exclusion criteria, the details of the randomization, and the results of primary and secondary outcomes of the study, are reported elsewhere.3 The institutional review boards at the University of California–San Francisco and Oregon Health and Science University approved this study; written informed consent was obtained from all participants.