Suvorexant and Trauma Related Insomnia
Condition: Insomnia; Posttraumatic Stress Disorder
MeSH terms: Sleep Initiation and Maintenance Disorders; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 4

Summary: 
      Problems sleeping are common after exposure to highly threatening experiences and can occur
      with and without a diagnosis of posttraumatic stress disorder (PTSD). Established treatments
      for PTSD are limited for addressing insomnia and many insomnia treatments appear to be
      limited in the context of PTSD. Suvorexant is FDA approved for insomnia and among approved
      drugs has a unique mechanism of action that may be well suited for targetting arousal at
      night dysregulated by trauma. The investigators will evaluate the efficacy of suvorexant for
      insomnia that developed in relation to trauma exposure, utilizing a placebo control, and
      polysomnography to identify biomarkers of response, in a six week trial.
    

Detailed description: 
      Disturbed sleep is one of the most common and distressing responses to exposure to severe
      trauma and can persist in many of those affected with and without accompanying posttraumatic
      stress disorder (PTSD). Insomnia is a risk factor for many of the conditions that are
      prevalent in trauma-exposed populations including PTSD, depression, and physical health
      conditions such as obesity, and cardiovascular disease. Trauma-related insomnia (TRI) is not
      typically differentiated in studies characterizing insomnia and its treatment, and insomnia
      accompanying PTSD has been shown to be relatively refractory to the treatments that are
      established for PTSD. Thus treatment of TRI presents an unmet need that has implications for
      the large and growing groups of people exposed to trauma in terms of relieving distress and
      preventing further psychiatric and medical morbidity.

      Most of the data on TRI comes from research on populations with PTSD. Difficulty initiating
      and maintaining sleep is designated as one of the heightened arousal symptoms of PTSD in the
      DSM. Sleep studies have suggested increased wake after sleep onset (WASO), reduced slow wave
      sleep (SWS) in some PTSD populations and fragmented rapid eye movement (REM) sleep when PTSD
      is developing, and during its more acute stages. Suvorexant is a first in class orexin
      antagonist and is approved by the FDA for the indication of insomnia. Orexin antagonists
      dampen the activity of a specific arousal enhancing system in the brain during sleep. In
      rodent models suvorexant has been shown to enhance, and in healthy humans, to not affect slow
      wave and REM activity (in contrast with traditional hypnotics which can diminish both).
      Reducing arousal during sleep while reducing WASO and maintaining REM and slow wave sleep is
      a promising profile for the treatment of TRI. We are therefore proposing a placebo controlled
      evaluation to assess the efficacy of suvorexant for treating TRI with and without PTSD and
      its tolerability in these populations. We will include polysomnography (PSG) in order to have
      objective sleep outcomes and probe potential mechanisms and biomarkers predicting response.
      The proposed study will meet the objective below and test the following hypotheses:

      Objective. To evaluate the efficacy of suvorexant for participants that meet criteria for
      insomnia and who identify a severely threatening event (DSM criterion A trauma) as a
      precipitant or a factor that significantly exacerbated their sleep disturbance.

      The investigators hypothesize that suvorexant will improve subjective and objective indices
      of sleep disturbance; specifically, our primary outcome the polysomnographic (PSG) measure of
      sleep efficiency will be increased in the group receiving suvorexant compared with the group
      receiving placebo.

      The effect of suvorexant versus placebo on the secondary outcome measures of the Insomnia
      Severity Index (ISI) scores and co-occurring symptoms of PTSD will also be evaluated.

      Exploratory analyses will include comparison of response patterns among those with versus
      without significant symptoms of PTSD and relationships between increased in slow wave and
      rapid eye movement (REM) sleep and improvement in ISI scores and PTSD symptoms.

      Adverse experiences and the tolerability of suvorexant in the recruited population with TRI
      will also be evaluated.
    

Intervention name(s): suvorexant; placebo
Intervention type(s): Drug; Other
Intervention description(s): First in class orexin antagonist recently approved by the FDA for the treatment of insomnia; Pill with inactive ingredients
Other intervention name(s): Belsomra
Intervention MeSH terms: Suvorexant
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment