The Effects of Orexin Antagonism on Fear Extinction in PTSD
VA Office of Research and Development
Summary
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.
Description
PTSD is a common consequence of combat manifested in part by trauma-related arousal and reactivity, seen in increased startle and impaired sleep that result from central and autonomic nervous system alterations. Impaired fear extinction may explain prolonged physiological alterations in PTSD. Preclinical evidence suggests that orexin, a wake-promoting neuropeptide, may be a shared mechanism underlying both sleep and fear extinction. While rodent studies have shown that pharmacological manipulations that block orexin in rodents facilitate fear extinction, no studies have tested this in humans w…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * (same for Phase 1 and Phase 2): * men and women * a history of US military service * capable of reading and understanding English * able to provide written informed consent * Criterion A event meets DSM-5 criteria and occurred during military service, including combat and military sexual trauma * Chronic full PTSD diagnosis \>3 months duration as indexed by CAPS-5 at screening, and CAPS-5 score \> 30 * Insomnia indicated by insomnia severity index (ISI) score \> 14 * Subjects on non-exclusionary medications, and must be on a stable dose for at least 4 weeks prio…
Interventions
- DrugSuvorexant
Suvorexant pills (10-20 mg)
- DrugPlacebo
Matching placebo pills
Locations (2)
- San Francisco VA Medical Center, San Francisco, CASan Francisco, California
- Ralph H. Johnson VA Medical Center, Charleston, SCCharleston, South Carolina