Riluzole augmentation may help veterans with PTSD who are resistant to SSRIs, SNRIs

Augmentation of selective serotonin or serotonin-noradrenaline reuptake inhibitors with riluzole may improve PTSD hyperarousal symptoms, according to study results published in Journal of Clinical Psychiatry.

This improvement appeared to occur without changes in overall PTSD symptoms, anxiety, depression or disability.

“Preclinical evidence suggests that riluzole facilitates fear extinction in rats, and a recent preliminary meta-analysis of clinical trials showed that riluzole had small positive effects on depression and obsessive-compulsive disorder symptoms, which have some commonality with PTSD symptoms,” Patricia T. Spangler, PhD, of the Center for the Study of Traumatic Stress at the Uniformed Services University in Maryland, and colleagues wrote. “These findings suggest that riluzole may be an effective pharmacologic agent in the treatment of PTSD.”

In the current randomized, double-blind, placebo-controlled, parallel trial, the investigators sought to determine the efficacy of augmenting SSRI and SNRI treatment with riluzole, a glutamatergic modulator approved for treating amyotrophic lateral sclerosis, for PTSD symptoms related to combat. They conducted the trial at two medical centers among veterans and active duty service members with combat-related PTSD according to results of the Clinician Administered PTSD Scale (CAPS). All participants were not responsive to SSRI or SNRI pharmacotherapy, and 36 were randomly assigned to 8-week augmentation with a starting dose of 11 mg per day of riluzole while 38 received placebo. The investigators assessed participants weekly for PTSD symptoms, anxiety, depression, disability and side effects.

Results of intent-to-treat analyses of CAPS scores revealed no significant differences between groups on change in overall PTSD symptoms, with a small effect size. However, Spangler and colleague noted clinically significant improvement within groups in overall PTSD symptoms for both groups. Both groups exhibited clinically significant within-group improvement in overall PTSD symptoms, but the riluzole group exhibited a greater mean decrease in CAPS score vs. the placebo group. Further, the riluzole group had significantly greater improvement on hyperarousal as measured by the PTSD Checklist-Specific-Subscale and near-significant findings on the CAPS Subscale D, according to exploratory analyses of PTSD symptom clusters. Change in depression, anxiety or disability were not significantly different between the riluzole augmentation and placebo groups.

“While these findings should be interpreted with caution, they indicate that riluzole may reduce hyperarousal symptoms in combat veterans whose PTSD symptoms did not remit with SSRI/SNRI monotherapy,” Spangler and colleagues wrote. “Despite the limitations of the current study, its results suggest that riluzole may have the potential to play such a role in treating combat-related PTSD. Further study of riluzole (and other glutamatergic modulators) will help clarify the role for such agents in treating PTSD unrelated to military combat.”