Active duty service members and veterans with post-traumatic stress disorder (PTSD) refractory to evidence-based therapy were randomized to receive either riluzole, a glutamate modulator, or placebo adjunctive to selective serotonin reuptake inhibitor therapy over an 8-week period. Subjects underwent 1H brain magnetic resonance spectroscopy scans pre- and post-treatment and were assessed longitudinally for PTSD symptomology using the Clinician-Administered PTSD Scale (CAPS). Subjects were stratified into improved and non-improved groups based on a decrease in CAPS score. Analyses on within- and between-group metabolite differences revealed that riluzole modulated the glutamate-glutamine cycle, improved neural energetics, and may have induced choline-linked neuroprotective inflammation.
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