Adding Trauma-focused Psychotherapy to Ketamine Treatment for Chronic PTSD
Condition: PTSD
MeSH terms: Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

Summary: 
      The current pilot project will evaluate the efficacy of adding Written Exposure Therapy (WET)
      to a course of repeated IV ketamine infusions in improving PTSD symptoms and maintaining
      symptom improvement in patients with chronic PTSD. WET is a brief, 5-session evidence-based
      written trauma-focused therapy without in between-session assignments, with demonstrated
      efficacy and low dropout rates in patients with PTSD. WET will be administered to all
      eligible participants; the first WET sessions will be interleaved with the last two ketamine
      infusions to take advantage of a window of increased neuroplasticity potentially induced by
      repeated ketamine infusions. WET will be administered on different days as the ketamine
      infusions.
    

Detailed description: 
      Current treatments for PTSD do not work for a significant proportion of individuals with
      PTSD, or work only partially, leaving persistent and disabling residual symptoms. The
      research team has led the development of ketamine for the treatment of chronic PTSD. After
      the initial, proof-of-concept randomized controlled trial (RCT) of a single ketamine infusion
      in individuals with chronic PTSD showed promising results, the study team recently completed
      the first RCT of repeated intravenous ketamine infusions where individuals with chronic PTSD
      received a course of six ketamine infusions (vs. active placebo midazolam infusions) and
      demonstrated a rapid and robust improvement in PTSD symptoms. Median time to loss of
      response, however, occurred a few weeks following the course of infusions, making it
      imperative to investigate novel approaches aimed at preventing symptom relapse following
      ketamine treatment. The study team proposes a proof-of-concept, open-label pilot study to
      evaluate the efficacy of adding an evidence-based, brief and scalable trauma-focused
      psychotherapy, Written Exposure Therapy (WET), to a course of ketamine infusions in improving
      PTSD symptoms and maintaining symptom improvement, in participants with chronic PTSD. To
      accomplish this aim, the study team will enroll individuals who meet DSM-5 criteria for
      chronic PTSD. Eligible patients will receive a total of six ketamine infusions and will
      participate in WET (a total of five sessions). The primary outcome will be change in PTSD
      symptom severity from baseline to 12 weeks from the start of WET, assessed with the
      Clinician-Administered PTSD Scale for DSM-5. Additionally, all participants will be assessed
      weekly until 12 weeks following the start of WET. Thereafter, participants who remain
      improved will be assessed monthly for up to 24 weeks. The study team will also evaluate
      whether extinction learning ability -assessed with a computerized extinction learning task-
      predicts maintenance of ketamine response over time, and will explore potential
      sociodemographic and clinical predictors of treatment response. If demonstrated to have
      preliminary efficacy, this novel combined treatment may represent a promising intervention
      for individuals with chronic PTSD, deserving further study.
    

Intervention name(s): Ketamine; Written Exposure Therapy
Intervention type(s): Drug; Behavioral
Intervention description(s): Repeated intravenous Ketamine infusions.; WET is a brief, 5-session evidence-based written trauma-focused therapy
Other intervention name(s): WET
Intervention MeSH terms: Ketamine
Intervention model: Single Group Assignment
Intervention model description: Open label pilot study
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ketamine; Written Exposure Therapy; PTSD; intervention; treatment; posttraumatic stress disorder