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Add-on Riluzole May Ease PTSD Hyperarousal Symptoms

November 03, 2020

Augmentation of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) treatment with the glutamatergic modulator riluzole may selectively improve hyperarousal symptoms in combat veterans with post-traumatic stress disorder (PTSD), according to a study published in the Journal of Clinical Psychiatry.

“Current pharmacologic treatments for PTSD have shown limited efficacy,” researchers wrote, “prompting a call to investigate new classes of medications.”

The double-blind trial included 74 US veterans and active duty service members with combat-related PTSD who were not responsive to SSRI or SNRI pharmacotherapy. Participants were randomized to either 8 weeks of add-on riluzole (100 mg a day) or placebo.

Although the study did not find a significant difference between treatment groups in overall symptoms, participants who received riluzole did show greater improvement in hyperarousal symptoms.

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Previous studies have linked hyperarousal symptoms with suicide attempts among combat veterans, explained study first author Patricia Spangler, PhD, a clinical research psychologist at Uniformed Services University, Bethesda, Maryland. Additionally, patients with high hyperarousal tend not to be as responsive to psychotherapeutic treatment for PTSD.

“Our results, though they should be interpreted cautiously, indicate that riluzole may reduce hyperarousal symptoms in combat veterans who are continuing to experience these symptoms despite treatment with antidepressants,” she said. 

If confirmed, the findings could be applicable to populations beyond combat veterans, noted study coauthor Army Col. David Benedek, MD, chair of the psychiatry department at Uniformed Services University. 

“At Uniformed Services University, we were particularly interested in the potential benefits of this medication for persons suffering from combat-related PTSD, as persistent symptoms may negatively impact military readiness,” he wrote. “But hyperarousal may have a negative social and occupational consequences in civilian life, so this augmentation strategy may hold promise for a wide range of persons suffering from residual PTSD symptoms.”

—Jolynn Tumolo


Spangler PT, West JC, Dempsey CL, et al. Randomized controlled trial of riluzole augmentation for posttraumatic stress disorder: efficacy of a glutamatergic modulator for antidepressant-resistant symptoms. Journal of Clinical Psychiatry. 2020;81(6):20m13233.

Motor neuron drug shows promise as treatment for PTSD symptoms linked to suicide attempts [press release]. Bethesda, Maryland: Uniformed Services University of the Health Sciences; October 27, 2020.

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