Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder

The purpose of this study was to assess the effects of the medication paroxetine on symptoms of posttraumatic stress disorder (PTSD) and the brain in women with a history of PTSD related to childhood abuse. The hypothesis is that paroxetine will result in an improvement in PTSD symptoms accompanied by changes in brain functional response to reminders of childhood trauma.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Drug: Paroxetine; Other: Positron Emission Tomography (PET) Imaging; Drug: Placebo

Detailed Description

The main purpose of this study was to look at the effects of paroxetine on PTSD symptoms and brain function in women with posttraumatic stress disorder (PTSD) related to childhood abuse. Participants underwent baseline assessment with of PTSD symptoms measured with the Clinician Administered PTSD Scale (CAPS) and brain function during exposure to traumatic scripts of childhood abuse. Participants then were treated in a randomized double-blind fashion with paroxetine or placebo for three months, followed by a repeat of these assessments.

Specific Aims of this proposal were therefore to:

• Assess the effects of paroxetine on PTSD symptoms
• Assess the effects of paroxetine on brain function in conjunction with exposure to traumatic scripts using positron emission tomography (PET) with O-15 water

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30306
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects meet criteria for current PTSD as determined by the Structured Clinical Interview for DSMIV (SCID) interview for PTSD and the Clinician Administered PTSD Scale (CAPS) and have a score of greater than 60 on the CAPS
• history of penetrative sexual abuse which occurred once a month or more, for a period of greater than a year at some time between the ages of 4-13, as assessed by the Early Trauma Inventory (ETI)
• are free of psychotropic medication for four weeks before the study (subjects will not be taken off of medication for the purpose of the study).
• Non-PTSD subjects will be included based on the same criteria with the exception that they do not meet criteria for PTSD.

Exclusion Criteria:

• a history of shrapnel or other foreign bodies which would preclude MRI scanning
• meningitis
• traumatic brain injury
• neurological disorder or organic mental disorder
• history of loss of consciousness
• alcohol abuse or substance abuse or dependence based on the SCID within the past 24 months
• positive pregnancy test as measured by a serum beta-HCG or urine pregnancy test on the morning of the PET scan. Women will be counseled about the risks of pregnancy during the course of the study
• current or lifetime history of schizophrenia, schizoaffective disorder, or bulimia, based on the SCID
• a history of serious medical or neurological illness, such as cardiovascular, gastrointestinal, hepatic, renal, neurologic or other systemic illness
• evidence of a major medical or neurological illness on physical examination or as a result of laboratory studies (CBC, BUN, creatinine, blood sugar, electrolytes, liver and thyroid function tests, urinalysis, and EKG)
• positive urine toxicology screen
• history of ongoing violence such as domestic abuse as measured by the ETI-lifetime
• post-menopausal status as measured by menstrual history.
• Non-PTSD subjects will additionally be excluded with current major depression or other major psychiatric disorder based on the SCID.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paroxetine Group; Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.	Drug: Paroxetine; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.; Other Names: Paxil; Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts
Placebo Comparator: Placebo Group; Women who have experienced early childhood abuse and have PTSD will be randomized in a double blind fashion to receive placebo for a three month period followed by an open label phase of paroxetine for three months.	Drug: Paroxetine; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.; Other Names: Paxil; Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts; Drug: Placebo; Following a three month double blind phase, subjects will be treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
Other: PTSD Negative; Women who have experienced early childhood abuse and do not have PTSD will serve as a control group and complete baseline assessments. They do not undergo intervention therefore they are assessed at baseline only.	Other: Positron Emission Tomography (PET) Imaging; Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score	The CAPS is a 30-item questionnaire of PTSD symptomatology that provides continuous measures of symptom severity and frequency. CAPS-IV total symptom severity score is calculated by summing severity scores for the 17 DSM-IV PTSD symptoms. Each symptom is rated for severity based on frequency and intensity on a scale of 0-4 for a total possible severity score per symptom of 8. Criterion E (items 18-19) is duration of symptoms (minimum of one month to make the diagnosis). Items 20-30 are optional. CAPS score is based on items 1-17, CAPS score has a potential range of 0-136, with higher scores indicating greater severity of PTSD symptoms. CAPS was performed before and after treatment with paroxetine or placebo in PTSD patients.	Baseline, End of Study (Up to 52 Weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)	Participants were exposed to traumatic scripts versus neutral scripts before and after treatment with paroxetine or placebo. Brain blood flow was measured using statistical parametric mapping (SPM) which analyzes brain imaging data sequences. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group. Data for each participant can not be generated using this software and therefore are not available to summarize in the data table below. Regional blood flow was compared for stress and neutral conditions and before and after treatment with paroxetine or placebo. Higher z-scores indicate an increase in regional blood flow to the medial prefrontal cortex under stress conditions for the 3 month time point relative to baseline. Statistical Parametric Mapping software is only capable of producing a single z-score for each Arm/Group.	Baseline, 3 Months Post Treatment

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: James D. Bremner, MD, PROFESSOR

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: September 6, 2012
• First Submitted That Met QC Criteria: September 6, 2012
• First Posted (Estimate): September 10, 2012

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: PTSD; childhood abuse
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: IRB00000857; R01MH056120 (U.S. NIH Grant/Contract)