Suvorexant 3 - PE-PC

Insomnia is the most prevalent symptom endorsed by PTSD patients and is highly prevalent in TBI, resulting in impairments in many domains of overall health and functioning. Prolonged exposure for primary care (PE-PC) is a shorter version of traditional PE that has demonstrated efficacy in the treatment of PTSD, related conditions (e.g., insomnia, depression), and improving functioning when compared to treatment as usual (e.g., PE, cognitive behavioral therapy for insomnia) in Veterans. However, challenges for PTSD interventions remain as some symptoms, particularly arousal and sleep-related difficulties, often fail to remit, with only 40-60% of Veterans showing clinically significant improvements following treatment, in addition to high attrition rates from these interventions. An integrated treatment that incorporates a pharmacological intervention that improves sleep during PE-PC may provide the greatest opportunity to facilitate recovery, by both increasing Veterans' engagement in treatment and supporting the extinction learning and consolidation mechanisms that promote recovery.

Hypothesis/Objective(s): The investigators aim to test whether integrating PE-PC with suvorexant, FDA-approved for the treatment of insomnia, will 1) promote the efficacy of PE-PC in improving sleep and PTSD symptoms in Veterans and military personnel with insomnia and posttraumatic stress disorder (PTSD) with and without mild-to-moderate traumatic brain injury (TBI); and 2) improve psychosocial and physical functioning.

Specific Aims: 1) To examine whether suvorexant facilitates PE-PC, seen as a greater reduction of PTSD symptoms over the course of treatment. 2) To examine whether suvorexant facilitates greater improvement in psychosocial and physical functioning compared to placebo over the course of treatment.

Study Design: The investigators propose an 8-week randomized, double-blind, placebo-controlled Phase IV clinical trial to examine the efficacy of augmenting PE-PC with suvorexant (10-20 mg) for the treatment of PTSD symptoms and improvement of functioning in Veterans with PTSD, insomnia, with and without TBI. The study design (N = 142) will involve repeated measures with two intervention arms, both of which include a standard course of weekly PE-PC therapy: 1) PE-PC+suvorexant (n = 71) compared to 2) PE-PC+placebo (n = 71).

Clinical Impact: This work aligns with the FY24 TBIPHRP CTA Research Level 2, Focus Area to Treat by examining repurposed interventions to improve outcomes of psychological health conditions and/or TBI through treatment and rehabilitation. The proposed intervention could promote sustained functional recovery following insomnia, PTSD, and TBI, as well as increased treatment engagement, retention, and success in those Veterans who would have otherwise not responded to treatment.

Relevance to Military Health: PTSD affects one in four treatment-seeking U.S. Veterans returning from Iraq and Afghanistan and one in 10 VA healthcare users. Sleep disturbance was the most frequently reported symptom in Veterans with PTSD, with the prevalence of insomnia or nonrestorative sleep estimated between 60%-90% and up to 97.4% of combat Veterans with TBI. However, effective and readily available treatments for co-occurring PTSD, insomnia, and TBI are not readily available or successful outside of PTSD specialty clinics, leading to unmet healthcare needs and/or treatment dropout/non-response. The ultimate goal of this work is to improve treatment availability and options for Veterans and military personnel affected by PTSD and TBI. Increased effectiveness of PTSD treatment in Veterans has the potential to: 1) optimize performance; 2) preserve health across the full deployment life cycle; and 3) improve long-term physical, social, and occupational functioning.

Inclusion criteria

• Adults 18-75 years who are U.S. military Veterans; able to read/understand English and provide written informed consent;
• Exposure to a DSM-5 Criterion A traumatic event;
• Current PTSD, duration > 3 months, CAPS-5 total score ≥ 12
• Insomnia diagnosis indicated by ISI score >14
• If taking non-exclusionary psychotropics (e.g., SSRI/SNRI, tetracyclic antidepressants, tricyclics, antipsychotics, and mood stabilizers, insomnia medication, neuroleptics, anti-psychotics) must be on a dose stable ≥ 4 weeks before randomization.
• If in supportive psychotherapy, stable ≥ 6 weeks before randomization (no concurrent exposure-based PTSD or CBT-I).
• Women of childbearing potential: negative urine pregnancy test at screening; agree to use a medically acceptable contraception method during treatment.

Exclusion criteria

• DSM-5 alcohol, marijuana, and/or other substance use disorder in the last 3 months. Mild alcohol and marijuana use not meeting criteria for disorder permissible;
• Lifetime bipolar disorder I or II, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features;
• Exposure to trauma in the last 3 months;
• Prominent suicidal or homicidal ideation, any suicidal behavior in the past 3 months on the Columbia Suicide Severity Rating Scale (C-SSRS)83, or increased risk of suicide that necessitates additional therapy or inpatient treatment;
• Pre-existing sleep apnea by type III device with AHI >15 in the absence of adherence to effective treatment (such as CPAP or oral device);
• Night shift work or extreme morning or evening tendencies;
• Neurologic disorder or systemic illness affecting CNS function;
• Chronic or unstable medical illness (i.e., angina, myocardial infarction within the past 6 months, congestive heart failure, preexisting hypotension or orthostatic hypotension, heart block or arrhythmia, chronic renal or hepatic failure, pancreatitis, and severe chronic obstructive pulmonary disease);
• Severe cognitive impairment as assessed by the MoCA (or alternative validated threshold per site SOP)
• Pregnancy or breastfeeding, or unwillingness to use effective contraception (women of childbearing potential).
• Previous adverse reaction to a hypnotic;
• Current use of sedative-hypnotics, benzodiazepines, moderate or strong CYP3A inhibitors, or strong CYP3A inducers or Digoxin;
• Current participation in exposure-based PTSD or behavioral insomnia treatments.