Clinical TrialPTSDEsketamineCompleted

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

This open-label, proof-of-concept trial (n=8) will investigate the feasibility and effects of combining intranasal esketamine (28-84mg) with Prolonged Exposure (PE) therapy for the treatment of post-traumatic stress disorder (PTSD). Participants will receive 10 sessions of PE in a massed format over two weeks, alongside esketamine administered six times (three times per week) approximately one hour after specific PE sessions.

Target Enrollment
8 participants
Study Type
Phase I/II interventional
Design
Non-randomized

Detailed Description

An early phase I/II, open-label, single-group pilot to evaluate feasibility, acceptability, and preliminary clinical effects of intranasal esketamine combined with massed Prolonged Exposure for individuals with PTSD.

Participants receive 10 individual PE sessions over 2 weeks with intranasal esketamine administered six times (~1 hour after selected PE sessions); outcomes include PTSD symptom change, safety/tolerability, and feasibility metrics.

Study Protocol

Preparation

sessions

Dosing

6 sessions
15 min each

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Esketamine + PE

experimental

Intranasal esketamine administered alongside massed Prolonged Exposure (PE) therapy (open-label, single group).

Interventions

  • Esketamine28 - 84 mg
    via Other• six doses over 2 weeks• 6 doses total

    Intranasal spray given ~1 hour after PE sessions 1,3,5,6,8,10; starting 28 mg (14 mg per nostril), escalated to 84 mg as three 28 mg bouts separated by 5 minutes (15 min total administration).

  • Compound
    via Other• daily PE sessions (weekdays)

    Massed Prolonged Exposure: 10 individual PE sessions delivered over 2 weeks (weekdays, not including weekends/holidays).

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion 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).

Exclusion Criteria

  • Exclusion Criteria:
  • 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.

Study Details

  • Status
    Completed
  • Phase
    Phase IPhase II
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment8 participants
  • Timeline
    Start: 2025-02-20
    End: 2025-12-30
  • Compound
    Esketamine
  • Topic
    PTSD

Locations

The University of Texas Health Science Center at San Antonio — San Antonio, Texas, United States

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