for people ages 18-75 (full criteria)
at San Francisco, California and other locations
study started
completion around
Principal Investigator
by Sabra S Inslicht, PhD
Headshot of Sabra S Inslicht
Sabra S Inslicht



Post-traumatic stress disorder (PTSD) is a common consequence of combat that can result in trauma-related hyperarousal and sleep disturbances. Poor sleep, one of the most common complaints in Veterans with PTSD, can be distressing, impair concentration and memory, and contribute to physical health conditions, such as metabolic syndrome, inflammation, and cardiovascular disease. The orexin neuropeptide system underlies both sleep and stress reactivity. Suvorexant, a drug that reduces orexin, improves sleep in civilians, but has not yet been tested in Veterans with PTSD. This study will test whether suvorexant can improve sleep disturbances and PTSD symptoms in Veterans. Suvorexant may benefit Veterans by improving sleep quickly while also reducing PTSD symptoms over the long term, and with fewer side effects that were common in previous medications used to treat these conditions. Improving Veterans' sleep and PTSD symptoms could lead to better emotional and physical well-being, quality of life, relationships, and functioning.

Official Title

Suvorexant: A Dual Orexin Receptor Antagonist for Treating Sleep Disturbance inPosttraumatic Stress


The investigators propose a multi-site parallel group, randomized, double-blind, placebo-controlled Phase IV clinical trial to test the efficacy and safety of suvorexant on trauma-related sleep disturbance and PTSD symptoms in Veterans. The investigators will use a flexible dose design of suvorexant with a 2-week titration followed by a 10-week steady-dose phase. The investigators predict that suvorexant, as compared to placebo, will result in a greater decrease in insomnia on the Insomnia Severity Index (ISI) over the 12-week trial. The investigators also predict that suvorexant, as compared to placebo, will result in a greater reduction in non-sleep PTSD symptoms in the Clinician Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSMV) (CAPS-5) over the 12-week trial. Secondarily, the investigators will examine potential objectively measured wrist actigraphy as a biological mechanism of clinical improvement with as well as concomitant effects on PTSD-related nightmares using the Pittsburgh Sleep Quality Index-PTSD addendum (PSQI-A). Pending a significant effect of suvorexant on PTSD, the investigators will perform exploratory analyses to evaluate whether sleep improvement mediates the effect of suvorexant on PTSD symptoms. The investigators will also examine safety and tolerability of suvorexant compared to placebo (including depression, mood, vigor, suicidality, and daytime somnolence, psychomotor vigilance, and functional disability). Results from this study will provide substantive rationale for the use of Suvorexant in the treatment of Veterans with these concerns. This study will be the first to examine a selective orexin-receptor antagonist in a Veteran sample with PTSD. Suvorexant is an accessible, non-stigmatized medication whose use and safety has been well-established in non-mental-health settings. It has outstanding promise for treating common and distressing symptoms in Veterans as well as civilians with trauma-related sleep disturbance and PTSD.


Sleep Initiation and Maintenance Disorders, Stress Disorders, Posttraumatic, Suvorexant, Veterans, Dyssomnias, Parasomnias, Traumatic Stress Disorders, Post-Traumatic Stress Disorders


You can join if…

Open to people ages 18-75

  • Men and Women, age range of 18 to 75, with a history of US military service, capable of reading and understanding English, and able to provide written informed consent
  • Criterion A event meets DSM-5 criteria
  • PTSD symptoms >3 months duration as indexed by a CAPS-5 12 and a partial PTSD diagnosis at screening
  • Insomnia indicated by an ISI score > 14
  • Subjects on non-exclusionary medications must be on a stable dose for at least 4 weeks prior to randomization, which includes the Selective Serotonin Reuptake Inhibitors (SSRIs) e.g.:
    • Sertraline
    • Paroxetine
    • Fluoxetine
    • Fluvoxamine
    • Citalopram
    • Escitalopram
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs), e.g.:
    • Desvenlafaxine
    • Duloxetine
    • Levomilnacipran
    • Venlafaxine
  • For subjects who are in psychotherapy, treatment must be stable for 6 weeks
  • Women of child-bearing potential must not be pregnant or have plans for pregnancy or breastfeeding during the study and must use a medically acceptable method of birth control, e.g.:
    • oral
    • implantable
    • injectable
    • transdermal contraceptive
    • intrauterine device
    • double-barrier method
  • Sleep apnea score <30; if screening indicates mild or moderate sleep apnea (score between 5 and 30), referral will be provided

You CAN'T join if...

  • DSM-5 alcohol, marijuana, and/or other drug use disorder in the last 3 months
    • Mild alcohol use not meeting criteria for moderate or severe use disorder may be allowed on a case-by-case basis
    • Mild or moderate marijuana use disorder may be allowed on a on a case-by-case basis
  • Manic or psychotic episode in the last 5 years
  • Exposure to trauma in the last 3 months
  • Prominent suicidal or homicidal ideation or any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS) or increased risk of suicide that necessitates additional therapy or inpatient treatment
  • Pre-existing severe sleep apnea (score >30) in the absence of adherence to effective treatment (such as CPAP or oral device) or positive screen for severe sleep apnea by type III device (score > 30)
  • Neurologic disorder or systemic illness affecting CNS function
  • Chronic or unstable medical illness including:
  • History of severe traumatic brain injury
  • Mild cognitive impairment assessed by the Montreal Cognitive Assessment
  • Pregnancy, breastfeeding and/or refusal to use effective birth control (for women)
  • Narcolepsy
  • Previous adverse reaction to a hypnotic
  • Current use of benzodiazepines, strong CYP3A inhibitors, or Digoxin


  • benzodiazepines
  • strong CYP3A inhibitors
  • Digoxin
  • Furthermore, CNS depressants (e.g., benzodiazepines, opioids, alcohol) increase the risk of CNS depression when co-administered with suvorexant and will not be allowed for safety reasons.
  • Since metabolism by CYP3A is the major elimination pathway for suvorexant, concomitant use of suvorexant with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan), moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil), or strong CYP3A inducers (e.g., rifampin, carbamazepine and phenytoin) will not be allowed.
  • All concomitant medication use will be monitored and documented


  • San Francisco VA Medical Center, San Francisco, CA accepting new patients
    San Francisco California 94121-1563 United States
  • VA Long Beach Healthcare System, Long Beach, CA not yet accepting patients
    Long Beach California 90822 United States
  • Salisbury W.G. (Bill) Hefner VA Medical Center, Salisbury, NC accepting new patients
    Salisbury North Carolina 28144 United States
  • Ralph H. Johnson VA Medical Center, Charleston, SC accepting new patients
    Charleston South Carolina 29401-5703 United States

Lead Scientist at UCSF

  • Sabra S Inslicht, PhD
    My research goals include: 1) identifying psychobiological causes and consequences of traumatic stress symptoms; 2) utilizing fear conditioning and extinction models to better understand PTSD; 3) characterizing sex differences in the biology of PTSD; 4) improving measurement techniques in the laboratory and the field such as with mobile health devices; and 5) conducting resear…


accepting new patients
Start Date
Completion Date
VA Office of Research and Development
Related Info
Phase 4 research study
Study Type
Expecting 144 study participants
Last Updated