Enhancing Week-long Psychological Treatment for PTSD With Ketamine

Based on the current research findings on the therapeutic effectiveness of trauma focus psychotherapy and of ketamine combining the two treatments may yield a promising new rapid week-long treatment for PTSD. As PTSD symptoms' structure is comprised of several unique clusters which include re-experiencing, avoidance, depression and hypervigilance the investigators hypothesize that by combining Ketamine with trauma-focused psychotherapy the proposed intervention can address these PTSD symptoms clusters more effectively than existing treatments. This proposed clinical trial has the potential to produce a significant therapeutic effect that otherwise would take months to occur by tapping on the enhanced neuroplasticity and the antidepressant effect of ketamine (which lasts between 24hrs to 7 days), to promote rapid changes in learning and memory when applying psychotherapy within a unique "window of opportunity" of neurophysiological changes produced by the investigative drug. During the first visit participants will undergo a clinical interview to establish a PTSD diagnosis and other eligibility criteria. If found eligible participants will be invited to take part in this 7-day rapid treatment trial for PTSD. On the first therapy visits, participants will be educated about the psychological treatment that will be provided and the potential benefit of ketamine or midazolam that may enhance the psychotherapy outcomes. On the second day of the study, participants will receive an infusion of ketamine or midazolam and will undergo a magnetic resonance imaging (MRI) to assess their brain reactivity to PTSD before the treatment. On days 3-6 participants will attend a 60-90 minutes psychotherapy session to address their PTSD symptoms. A second ketamine or midazolam infusion will take place on day 4 of the study to enhance the drug therapeutic effect for the study duration. Day 7 will include another MRI scan to assess treatment effect on PTSD. Participants will need to attend one follow up MRI scan and clinical evaluation at 30 days and then a clinical evaluation at 90 days post-treatment to assess the long-term effectiveness of the intervention.