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Orexin A 2026-06-01 ClinicalTrials

Orexin-receptor antagonist suvorexant to be evaluated for enhancing fear extinction in Veterans with **PTSD**

The Effects of Orexin Antagonism on Fear Extinction in PTSD

Background

PTSD affects approximately 22% of Veterans, manifesting as re-experiencing, avoidance, negative thoughts, and hyperarousal. Current treatments primarily leverage fear extinction principles, involving repeated exposure to feared cues to diminish physiological reactions. However, these therapies often have limited efficacy for many. Orexin, a wake-promoting neuropeptide, is known to modulate stress responses and has been suggested to enhance fear extinction. Targeting the orexin system presents a novel therapeutic avenue to improve PTSD outcomes by directly influencing this critical recovery process.

Study Design

This proposed study will examine whether suvorexant, a selective orexin-receptor antagonist, enhances fear extinction in Veterans diagnosed with PTSD and co-occurring insomnia. The primary objective is to assess suvorexant's impact on fear extinction, a core mechanism underlying recovery from PTSD. Secondary objectives include evaluating objective sleep improvements via wrist actigraphy and effects on PTSD-related nightmares using the Pittsburgh Sleep Quality Index-PTSD addendum (PSQI-A). Specific dosages, study duration, or participant numbers are not detailed.

Why It Matters

If this study demonstrates efficacy, suvorexant could become a valuable, accessible, and safe adjunct therapy for Veterans with PTSD, particularly those experiencing comorbid insomnia and impaired fear extinction. This research aims to validate a novel mechanistic approach to PTSD treatment, moving beyond traditional exposure therapies by targeting underlying neurobiology. Given suvorexant's established safety profile and widespread use for insomnia, positive findings could significantly accelerate its repurposing for PTSD, potentially improving treatment adherence and overall recovery. It could provide a new pharmacological strategy to augment existing fear extinction-based protocols.


suvorexant orexin antagonist ptsd fear extinction insomnia veterans
Source: clinicaltrials:NCT06788522 · Ingested 2026-06-09 · Digest: gemini-2.5-flash