Neural Correlates of Early Intervention for Posttraumatic Stress Disorder (PTSD)
Background: Innovation: Over 150,000 soldiers are currently deployed in Iraq as part of Operation Iraqi Freedom (OIF), and 12% of returning OIF veterans have posttraumatic stress disorder (PTSD). Research from our group and others showed lasting neurobiological consequences of PTSD, including increased amygdala function and decreased medial prefrontal function, verbal declarative memory problems, and smaller hippocampal volume that reverses with treatment with the serotonin reuptake inhibitor (SSRI) paroxetine or the anticonvulsant phenytoin. Recently we found that three months of treatment with paroxetine in PTSD patients resulted in an increase in hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity, as well as decreased brain metabolism in the amygdala and a reversal or stress induced decreases in medial prefrontal function. Subjects treated with placebo did not have an increase in NAA, however subsequent treatment for three months with open label paroxetine resulted in an increase in NAA to the level seen in the subjects treated with paroxetine in the double-blind phase. Paroxetine was associated with a decrease in amygdala metabolism measured with positron emission tomography (PET) and increased medial prefrontal function. Intervening soon after the trauma is critical for long-term outcomes, since with time traumatic memories become indelible and resistant to treatment. Diminished efficacy of treatment over time is shown by the fact that trials of Vietnam veterans have shown less efficacy over the years. Animal studies show that pretreatment before stress with antidepressants reduces chronic behavioral deficits related to stress; although for ethical and other reasons no studies have provided pretreatment before trauma exposure in humans. In our current VA Merit funded program we are looking at the effects of early interventions for Iraq soldiers with paroxetine, looking at chronicity of PTSD, cognition, cortisol response to stress, hippocampal volume and NAA, as outcomes. We now propose to add measurement of neural correlates of paroxetine response using PET.
Objectives/Hypotheses: The objectives of this research are to:
- Assess the efficacy of paroxetine versus placebo in the treatment of early PTSD in OIF veterans
- Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD.
- Assess the ability of brain imaging to predict treatment response and to identify veterans with early PTSD who will benefit from early interventions.
Hypotheses are that paroxetine will be associated with: 1) an improvement in PTSD symptoms compared to placebo based on the change in the CAPS from baseline to three months of treatment in veterans of OIF; 2) increased medial prefrontal function and decreased amygdala metabolism in veterans of OIF.
- Compare paroxetine to placebo in the treatment of early PTSD in OIF veterans
- Measure amygdala metabolism and medial prefrontal response to stress with PET in OIF veterans with PTSD before and after paroxetine or placebo treatment.
Posttraumatic Stress Disorder (PTSD)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Neural Correlates of Early Intervention for PTSD|
- PTSD symptoms as measured with the CAPS [ Time Frame: three months ]
- Assess the effects of paroxetine versus placebo on amygdala metabolism and medial prefrontal response to stress in OIF veterans with PTSD. [ Time Frame: three months ]
|Study Start Date:||April 2008|
|Study Completion Date:||March 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
treatment for three months with paroxetine
Placebo Comparator: 2
treatment for three months with placebo
Please refer to this study by its ClinicalTrials.gov identifier: NCT00665678
|United States, Georgia|
|Atlanta, Georgia, United States, 30306|
|Principal Investigator:||James D Bremner, MD||Emory University|