Suvorexant and fear learning in veterans with PTSD and insomnia

Who can take part

• (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 prior to randomization, including 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

Who cannot take part

• Moderate or severe DSM-5 alcohol or cannabis use disorder in the last 3 months; Mild alcohol use disorder with abstinence of 30 days will be allowed; Mild marijuana use disorder will be allowed with abstinence for one week prior to participation; Any other DSM-5 drug use disorder in the last 3 months will be excluded
• Use of exclusionary antidepressant (trazodone, mirtazapine, doxepin, tricyclics), mood stabilizers (e.g., lithium), antipsychotic medication
• 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
• Previous adverse reaction to a hypnotic
• Current use of benzodiazepines, strong inhibitors of CYP3A, or Digoxin; The investigators will require that all participants do not consume heavy amounts of alcohol per week (>7 drinks for women, >14 drinks for men) or use illicit drugs for one week prior to participation
• Lifetime bipolar disorder I or II, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, or major depressive disorder with psychotic features
• Neurologic disorder or systemic illness affecting CNS function
• Chronic or unstable medical illness, including:; unstable 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; severe chronic obstructive pulmonary disease
• History of severe traumatic brain injury as assessed by the Ohio State University Traumatic Brain Injury Identification Method (OSU-TBI ID)
• Uncorrected hearing impairment
• Mild cognitive impairment assessed by the Montreal Cognitive Assessment (MOCA)
• Exposure to trauma in the last 3 months
• 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)
• Night shift work or extreme morning or evening tendencies in order to avoid the impact of circadian factors on subjective and objective sleep measures
• Pregnancy, breastfeeding and/or refusal to use effective birth control (for women)