Prolonged Exposure for Post Traumatic Stress Disorder (PTSD) With/Without Yohimbine
Condition: Post-Traumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

Summary: 
      The proposed study has three distinct but related research objectives. The first goal is to
      measure physiological correlates of successful treatment with Prolonged Exposure (PE) therapy
      for posttraumatic stress disorder (PTSD) in veterans of the Iraq and Afghanistan wars.
      Individuals with PTSD often experience elevated heart rates and other objectively measurable
      signs of anxiety when confronted with safe situations that remind them of past dangerous
      situations. We will measure physiological responses and compare the outcomes to patient's
      self reported subjective accounts of symptom improvement on traditional measures of PTSD.
      Developing a way to measure objective gains in symptoms improvement may help researchers who
      are studying ways to improve PTSD treatment. The second goal of the study is to investigate
      if yohimbine, a drug found to promote a specific type of learning, will improve treatment
      outcomes for veterans in PTSD treatment. The third goal is to investigate if ability to get
      used to loud startling audio tones correlates to baseline PTSD pathology and treatment
      outcomes for PE. This goal represents an important step forward in understanding
      characteristics of heritable traits that are related PTSD. It is significant because such
      research may one day lead to the development of individual responder policies that will
      assist patients by individualizing treatment plans based on personal characteristics.
    

Detailed description: 
      The proposed study has three distinct but related research objectives. The first research
      goal is to measure psychophysiological correlates of treatment gains associated with
      Prolonged Exposure (PE) therapy for PTSD in veterans of Operations Enduring Freedom and Iraqi
      Freedom (OEF/OIF). Specifically, heart rate, heart rate variability, skin conductance, and
      facial electromyography, will be recorded before and after treatment during a three minute
      anxiety probe specific to the patient's index trauma. These measures will be compared to
      patient's self reported subjective accounts of symptom improvement on traditional measures of
      PTSD pathology (Subjective Units of Distress (SUDs), PTSD Checklist-Military Version (PCL),
      Clinician Administered PTSD Scale (CAPS), and the Beck Depression Inventory (BDI)). This goal
      is significant for veterans because currently no widely used objective criteria exist to
      measure treatment progress in PTSD. While the preponderance of existing evidence suggests
      that no one objective psychophysiological measurement will be a valid correlate for all
      individuals, even establishing a measurement paradigm that can show mean differences between
      groups will provide researchers with an objective tool to measure outcomes on clinical
      trials.

      The second goal of the study is to investigate if the administration of yohimbine, a drug
      found to promote the extinction of conditioned fear in animal models, and more recently, in
      humans with claustrophobia, improves the facilitation of fear extinction in PE. Yohimbine is
      a safe drug that is already extensively used in human populations. Specifically, this goal
      will be investigated using a double blind placebo controlled randomized trial design. The
      hypothesis is that one 21mg oral dose of yohimbine given concurrently with a 40 minute
      imaginal exposure exercise in PE will lead to a greater reduction in cue-induced anxiety
      during the following weekly PE session than placebo. This goal is significant because current
      projections of PTSD in OEF/OIF veterans indicate that the need for psychological services
      will likely outpace the supply of such services. Accordingly, assisting treatments to be more
      efficient will likely translate into more veterans receiving much needed mental health
      services.

      The 3rd goal is to investigate if ability to habituate to loud, 95db, audio tones correlates
      to baseline PTSD pathology and treatment outcomes for PE. This goal represents an important
      step forward in understanding characteristics of trait habituation, fear extinction, and
      learning in humans, which are all factors related to the successful treatment of PTSD. It is
      also significant because such research may lead to the development of individual responder
      policies that will assist veterans by individualizing treatment plans based on personal
      characteristics.
    

Intervention name(s): Yohimbine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): alpha-2 adrenergic receptor antagonist; Placebo
Intervention MeSH terms: Yohimbine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: PTSD; Prolonged Exposure; extinction; habituation; psychophysiology