Posttraumatic Stress Disorder, Combat-related Clinical Trial
Official title:
Predictors of Treatment Response to Fluoxetine in PTSD Following a Recent History of War Zone Stress Exposure
Three hundred (300) male or female outpatients, over 18 years of age, will be enrolled in this study to determine whether fluoxetine can be used as a treatment for Posttraumatic Stress Disorder in soldiers recently returning from combat exposure. There will be two phases to the study. In Phase I Fluoxetine + usual psychological care will be compared with Placebo + usual psychological care over a 12-week period. Subsequently, in Phase II all subjects will be offered the opportunity to enroll in a 20-week open-label trial on Fluoxetine. If response is inadequate, adjunctive treatment with either buspirone or bupropion will be offered. The investigational drugs are Fluoxetine, Buspirone and Bupropion. All are commercially available.
While most soldiers exposed to the stresses of the war-zone exhibit psychological
resilience, about one-fifth become psychological casualties of war. The fact that such a
significant number of soldiers have difficulty adapting to life after war exposure suggests
that we need to have well-defined treatments that are effective and cost-efficient.
Currently, recommendations for first-line pharmacological management of Post-Traumatic
Stress Disorder focus on the use of selective serotonin re-uptake inhibitors (SSRIs) such as
fluoxetine. Despite this recommendation by the DoD/VA Clinical Practice Guidelines, there
have not been any studies evaluating the effectiveness of these medications in patients that
have recently been exposure to war-zone stressors. In fact, studies in Vietnam Era veterans
have shown limited effectiveness of SSRIs for PTSD. In addition, there is very limited
information available to understand the factors that influence whether a particular soldier
will respond to treatment with an SSRI. This study is designed to determine whether
fluoxetine is an effective treatment for PTSD and associated conditions in soldiers with
recent war-zone exposure, as well as determine whether response to SSRIs is related to the
severity of the trauma exposure and PTSD symptoms, psychological resilience, adequacy of
social supports (family, extra-military and military), post-deployment stressors and life
adversity, or the degree of any cognitive impairment.
After informed consent is given, fluoxetine (150 subjects) or placebo (150 subjects) will be
administered for 12 weeks in doses from 20 mg daily up to 60 mg daily to active duty
soldiers who are already receiving usual psychological care in the Resilience and
Restoration Center of the Carl R. Darnall Army Medical Center at Ft. Hood. At the conclusion
of this initial phase of the study, all participants will receive fluoxetine in doses up to
80 mg daily for an additional 20 weeks. All participants will be regularly monitored to
determine changes in their PTSD symptoms. If a subject does not have at least a 50%
improvement after being given 80 mg daily of fluoxetine for 4 weeks, then they will be
randomly assigned to also receive either bupropion SR (150 mg daily) or buspirone (up to 40
mg daily) in an attempt to amplify the response to fluoxetine. Statistical analyses will be
used to determine which factors provided the greatest influence on the response to these
medication trials.
Each subject will be asked to receive a physical exam, give medical history information, and
receive a diagnostic interview prior to participation in the study. After being randomly
assigned to treatment, subjects will have interview or questionnaire assessments at weeks 2,
4, 6, 8, 12, 16, 20, 24, 28 and 32. Based solely on the degree of response as measured by
the PTSD Checklist (a questionnaire that will be administered at each study visit), the
dosage of study medication fluoxetine or placebo capsules will be adjusted by a
pre-determined schedule.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment