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
Intervention: Yohimbine; Placebo
Intervention description: alpha-2 adrenergic receptor antagonist; Placebo
Intervention MeSH terms: Yohimbine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: Male
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: PTSD; Prolonged Exposure; extinction; habituation; psychophysiology

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be competent to provide informed consent for research participation.

          -  Subjects must be male veterans and post deployed active duty male personnel of
             OEF/OIF.

          -  Subjects must be between the ages of 18 and 45.

          -  Subjects must meet DSM-IV diagnostic criteria for PTSD on the CAPS.

          -  For subjects taking SSRI's, subjects must be stabilized on the current prescribed dose
             for a period of at least 14 days prior to the trial and remain at that dose for the
             remainder of the study. Subjects who change their SSRI status or dosage during the
             study will continue to receive services via the study resources but data generated
             will not be used in analyses. Subjects will be eligible for the study if they are
             willing to titrate off potentially confounding agents prior to yohimbine
             administration (for a period of five half-lives), given that such titration is also
             clinically appropriate and deemed to be in the patient's best interests.

        Exclusion Criteria:

          -  Subjects with a recent (< 2 month) history of psychiatric hospitalization or suicide
             attempt. Recent work with veterans with severe mental illness suggests that a 2-month
             period of stabilization is sufficient to minimize risk and possible relapse (Frueh,
             2005). Subjects with an existing diagnosis of schizophrenia or other Axis I serious
             mental illnesses (SMI, besides PTSD) will be excluded. SMI will include any severe and
             persistent mental illness.

          -  Subjects with a current diagnosis of drug dependence, due to potential interactions
             with study measurements and treatments. Alcohol use disorders will be allowed given
             that subjects can pass exclusion criterion 12 without withdrawal symptoms.

          -  Subjects with any acute illness or fever. Individuals who otherwise meet study
             criteria will be rescheduled for evaluation for participation.

          -  Subjects with evidence of or a history of clinically significant hematological,
             endocrine, cardiovascular, hepatic, pulmonary, renal, gastrointestinal, or
             neurological disease including diabetes, as these conditions may affect
             physiological/subjective responses.

          -  Subjects with SCID-diagnosed panic disorder, as yohimbine may precipitate panic
             attacks.

          -  Subjects with an abnormal ECG.

          -  Subjects with a blood pressure of 140/90 or higher, as yohimbine has been shown to
             elevate blood pressure.

          -  Subjects taking Beta blockers, alpha-adrenergic agents, Beta-agonist inhalers, opiates
             or opiate antagonists and any psychotropic medications other than SSRI's because these
             may affect test response.

          -  Subjects who are unwilling or unable to maintain abstinence for three days prior to
             yohimbine administration from over-the-counter drugs with sympathomimetic properties,
             e.g., asthma medications, cold medicines with ephedrine, dietary supplements with
             ephedrine alkaloids, and illegal drugs, e.g., amphetamines, methamphetamine, cocaine,
             and MNDA as well as alcohol because these may exacerbate the action of yohimbine.

          -  Subjects taking alpha-adrenergic antagonists, e.g. prazosin for hypertension; and
             beta-adrenergic antagonists, e.g. propranolol. Because they may attenuate effects of
             yohimbine. Subjects will be eligible for the study if they are willing to titrate off
             potentially confounding agents prior to yohimbine administration (for a period of five
             half-lives), given that such titration is also clinically appropriate and deemed to be
             in the patient's best interests.

          -  Asthmatic subjects and subjects on medications for hypertension, due to criteria 9 and
             10.

        These inclusion/exclusion criteria will allow the majority of veterans treated in the PCT
        to be study eligible. Accordingly, the sample will be likely generalizable to the
        population of interest.