Clinical Research Directory

Inclusion Criteria: 1. Ability to comprehend and provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study (approximately 17 weeks from the date of being randomized) 3. Individuals, between the ages of 18 and 75 years 4. Allow digital recording of phone interviews 5. PTSD related to military service 6. Primary DSM-5 diagnosis of PTSD, assessed by structured interview using the CAPS-5 7. Total CAPS-5 score 23 8. ISI \>15 9. Screening clinical laboratory tests without clinically significant abnormalities that would make study participation inappropriate, as determined by the site investigator with input, if needed, from the study chair 10. Electrocardiogram (ECG) at baseline without clinically significant abnormalities that would make study participation inappropriate, as determined by the site investigator with input, if needed, from the study chair and/or contingent upon approval by consulting medical physician. 11. Females of childbearing potential: 1. Must have a negative pregnancy test during screening 2. Must agree not to become pregnant or breastfeed during the course of the study 3. Must be willing to use a reliable form of contraception for 16 weeks (during study treatment and for 2 weeks after taking the last dose) which includes: barrier contraceptives (male or female condoms with or without a spermicide, diaphragm or cervical cap with spermicide, or intrauterine device) and hormone-based therapy (contraceptive pills, intrauterine devices, or Depo-Provera®) 4. Birth control for female participants is not necessary if surgically sterile or if with a partner with whom they are not capable of conceiving children (defined as a surgically sterile female by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; surgically sterile male who has undergone a complete orchiectomy or successful vasectomy; or a same sex partner) 12. Agree to secure firearms while receiving study treatment 13. If individuals are undergoing evidence-based psychotherapy (EBT), which includes cognitive behavioral therapy (CBT), cognitive processing therapy (CPT), prolonged exposure therapy (PE), and/or stress inoculation therapy (SIT), they must have started these therapies at least 60 days prior to starting screening. If screening is started, and it is then discovered that EBT was started within 60 days prior to screening, participants must wait at least 60 days since staring the new EBT before they can complete the screening ISI, the screening PCL, and the Phone Assessment. (Supportive individual and group therapy is allowed) 14. Agreement to adhere to Lifestyle Considerations (see Section 5.3) throughout study participation 15. Clinical evidence of adequately treated sleep apnea or absence of sleep apnea having a severity that would make study participation problematic, established by meeting one of the criteria below: 1. Clinical evidence of adequately treated sleep apnea with a continuous positive airway pressure (CPAP) or alternative treatment device (as defined in Section 8.1) (Participants can be reevaluated at least 30 days after screen failure.) 2. If clinically tested, sleep study negative for sleep apnea or results indicating an Apnea-Hypopnea Index (AHI) \< 23 within the past 6 months 3. If tested for study eligibility, ApneaLink (or equivalent alternative device) result or other sleep study shows AHI \< 23. Exclusion Criteria: 1. Currently enrolled in any other interventional study unless prior approval is provided by the study team (It is a CSP policy that exemptions will be assessed for individual patients on a case-by-case basis. Exemptions require the agreement in writing of the following individuals or groups: (1) the SIs of both studies; (2) the Study Chairs of the involved studies; (3) the appropriate CSP Center Director(s); and (4) the VA Central IRB.) 2. Allergy and/or history of intolerance to trazodone hydrochloride and/or eszopiclone, or history of experiencing complex sleep behaviors (i.e., sleep walking, sleep driving, and/or engaging in other activities while not fully awake) while taking any sleep medication 3. A comorbid current or lifetime diagnosis of bipolar I disorder, bipolar II disorder, schizoaffective disorder, schizophrenia or delusional disorder, or current comorbid diagnosis of schizophreniform disorder, brief psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder or psychotic disorder not otherwise specified (NOS) according to Structured Clinical Interview for DSM-5 (SCID)-I-RV/P 4. History of moderate or severe traumatic brain injury (TBI) or history of gross structural damage as shown on MRI. 5. Positive urine test for an illicit substance, excluding cannabis, within the past 90 days prior to screening 6. Substance use meeting DSM-5 criteria for moderate or severe dependence (excluding nicotine) within the past 12 months prior to screening. (Note: Current mild dependence for alcohol and cannabis use is acceptable, but current mild dependence of any other substances is exclusionary.) 7. Inpatient psychiatric hospitalization within 30 days prior to screening 8. Suicidal or homicidal ideation with intent or plan to harm themselves or others within 90 days prior to screening 9. Chronic liver disease with two or more of the following occurring within the past six months: international normalized ratio (INR) greater than or equal to 1.7 (not on warfarin therapy), bilirubin greater than or equal to 2 mg/dL, serum albumin less than or equal to 3.5 g/dL, ascites, or encephalopathy (Participants can be reevaluated in 30 days) 10. Clinical and laboratory evidence of untreated hypothyroidism or hyperthyroidism 11. A corrected QT (QTc) interval greater than 470 ms 12. Unstable, serious medical condition or one requiring acute medical treatment, or planned hospitalization for extended care 13. Dementia, epilepsy, stroke, or current treatment with warfarin for anticoagulation 14. Taking any of the exclusionary medications listed in Appendix A. Note- an individual taking one of these medications for the sole purpose of improving sleep that elects to undergo an adequate wash-out period of at least 5 half-lives of the parent compound or active metabolite (e.g., for medications like diazepam), under the care of the individual's clinical provider, would not be excluded by this criterion. 15. Under criminal investigation or pending legal charges with potential incarceration 16. Individuals who lack stable contact information (including lack of a telephone number) 17. Participants who anticipate working during the hours of midnight to 6am during the course of study trial 18. Participants with narcolepsy