Suvorexant for Post-Traumatic Stress Disorder

Recruiting at 1 trial location

Overseen By Sabra S Inslicht, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: SSRIs, SNRIs

Must not be taking: Trazodone, Mirtazapine, Antipsychotics

Disqualifiers: Alcohol use disorder, Bipolar, Schizophrenia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 nights

40120 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You can continue taking certain medications like SSRIs and SNRIs if you have been on a stable dose for at least 4 weeks before joining the trial. However, you must stop using certain antidepressants, mood stabilizers, antipsychotics, benzodiazepines, and some other medications before participating.

How is the drug Suvorexant unique for treating PTSD?

Suvorexant is unique because it is a dual orexin receptor antagonist (DORA) that helps improve sleep by reducing arousal and enhancing REM sleep, which is different from most other treatments that may not target these specific sleep mechanisms. ^{1 2 3 4 5}

Research Team

Sabra S Inslicht, PhD

Principal Investigator

San Francisco VA Medical Center, San Francisco, CA

Eligibility Criteria

This trial is for Veterans with PTSD and insomnia, focusing on those who experience symptoms like re-experiencing trauma, avoidance, negative thoughts or feelings, and hyperarousal. The study seeks participants who have not found relief through standard treatments.

Inclusion Criteria

Capable of reading and understanding English

Insomnia indicated by insomnia severity index (ISI) score > 14

Able to provide written informed consent

Exclusion Criteria

Pre-existing moderate sleep apnea or positive screen for sleep apnea by type III device (AHI>15) in the absence of adherence to effective treatment (such as CPAP or oral device)

Exposure to trauma in the last 3 months

I have a brain condition or illness affecting my nervous system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Proof-of-Concept

Development and establishment of feasibility of the task and recruitment in 40 eligible participants with PTSD and insomnia. Involves a home-based multi-day remote fear conditioning experimental study.

23 months

Remote procedures

Treatment

Participants receive nightly doses of suvorexant or placebo following extinction training over 6 nights.

6 nights

Remote procedures

Follow-up

Participants undergo extinction retention and fear reinstatement tests one week after extinction.

1 week

Remote procedures

Treatment Details

Interventions

• Suvorexant

Trial Overview The study tests if Suvorexant (a medication that blocks a brain chemical promoting wakefulness) can help reduce PTSD symptoms by enhancing fear extinction—a process where repeated exposure to feared cues without danger lessens physiological reactions.

Participant Groups

Group I: Suvorexant Experimental Treatment 1 Intervention

Suvorexant pills (10-20 mg)

Group II: Placebo Placebo Group 1 Intervention

Matching placebo pills

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a 6-week double-blind, placebo-controlled trial with 37 participants suffering from trauma-related insomnia, suvorexant treatment showed significant improvements in PTSD and insomnia symptoms, although the strong placebo response made it difficult to determine the medication's specific effects.

Suvorexant was well tolerated, with only one participant dropping out due to side effects, and it was associated with increased REM sleep duration, which correlated with a reduction in PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of suvorexant for trauma-related insomnia. Mellman, TA., Birku, K., Sandhu, I., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Evaluation of suvorexant for trauma-related insomnia. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Assessment of the Abuse Potential of the Orexin Receptor Antagonist, Suvorexant, Compared With Zolpidem in a Randomized Crossover Study. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

Suvorexant: efficacy and safety profile of a dual orexin receptor antagonist in treating insomnia. [2017]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Effect of CYP3A Inhibition and Induction on the Pharmacokinetics of Suvorexant: Two Phase I, Open-Label, Fixed-Sequence Trials in Healthy Subjects. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Suvorexant: a novel therapy for the treatment of insomnia. [2015]