The Effects of Orexin Antagonism on Fear Extinction in PTSD

PTSD affects approximately 22% of Veterans who have served in Iraq and Afghanistan. Symptoms of PTSD may include re-experiencing, avoidance of trauma reminders, negative thoughts or feelings, and hyperarousal, such as increased startle reactivity and disturbed sleep. Treatments for PTSD are based on fear extinction principles in which individuals are repeatedly exposed a feared cue in the absence of danger, resulting in diminishing physiological reactions, a process believed to underlie recovery from PTSD. Studies suggest that orexin, a wake-promoting neuropeptide, may enhance fear extinction. This study will examine whether suvorexant, a selective orexin-receptor antagonist, will enhance fear extinction in Veterans with PTSD and insomnia. Finding a role for orexins in fear extinction will support the rationale for its further evaluation in the treatment of PTSD. Suvorexant is an accessible, safe medication that has been well-established in treating insomnia. It has outstanding promise for treating common and distressing symptoms in Veterans with PTSD.

NCT Number	NCT06788522
Lead Sponsor	VA Office of Research and Development
Conditions	Insomnia, PTSD
Enrollment	40,120 participants
Start Date	2026-06-01
Primary Completion	2032-03-01 (estimated)
Study Completion	2032-06-30 (estimated)
Updated on ClinicalTrials.gov	2026-06-02