Combining Esketamine and Prolonged Exposure Treatment for PTSD (Post Traumatic Stress Disorder)

Eligibility Criteria

• 1. Individual between the ages of 18-65 years old (Young adults \[18 to 24 years old\] must not be taking an antidepressant).
• 2. PTSD diagnosis as assessed by Clinician-Administered Posttraumatic Stress Scale (CAPS-5)
• 3. Able to speak and read English (due to standardization of outcome measures)
• 4. On stable doses of current medications for at least 4 weeks
• 5. Weigh between 50-100 kg (110-220 pounds).
• 1. Young adults (18-24) currently taking any antidepressant.
• 2. Lifetime history of psychotic disorder or history of significant psychotic symptoms.
• 3. Lifetime history of manic episode.
• 4. Moderate or greater severity for alcohol or substance use disorder (DSM-5) in the previous six months.
• 5. A history of ketamine or phencyclidine abuse.
• 6. Evidence of a traumatic brain injury severe enough to interfere with comprehension and responding to the baseline screening questionnaires.
• 7. Current suicidal ideation severe enough to warrant immediate attention (as determined by the Depressive Symptoms Index-Suicidality Subscale and corroborated by a clinical risk assessment by a credentialed provider)
• 8. Other psychiatric disorders severe enough to warrant designation as the primary disorder as determined by clinician judgment.
• 9. Current use (with past 4 weeks) of any prohibited concomitant medications
• 10. Benzodiazepines, other medications, sedatives, acute alcohol use, or recreational drug use that would put patients at risk in the judgment of clinical providers).
• 11. Planned use of ketamine (i.e., for pain control) or participation in another trauma-focused psychotherapy during the time of the study.
• 12. Uncontrolled hypertension or tachycardia
• 13. A history of sensitivity or adverse reaction to ketamine or its excipients
• 14. An unstable medical, cardiovascular, pulmonary, or neurological condition that the investigator considers a contraindication to ketamine administration
• 15. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
• 16. Intracerebral hemorrhage.
• 17. Pregnancy or breastfeeding; women of childbearing potential unwilling to utilize reliable methods of contraception
• 18. History of nasal surgery or nasal obstructions experienced as an adult.
• 19. Inability to arrange for assisted transportation on ketamine treatment days due to recommendation that patient not drive for the remainder of the day following a ketamine treatment.