Neural Circuits in Women With Abuse and Posttraumatic Stress Disorder

Phase 4

Completed

Conditions: PTSD

Interventions: Drug: Placebo
Drug: Paroxetine
Other: Positron Emission Tomography (PET) Imaging

Registration Number: NCT01681849

Lead Sponsor: Emory University

Brief Summary: 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 91

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Paroxetine Group	Positron Emission Tomography (PET) Imaging	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.
Placebo Group	Placebo	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.
Placebo Group	Positron Emission Tomography (PET) Imaging	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.
PTSD Negative	Positron Emission Tomography (PET) Imaging	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.
Paroxetine Group	Paroxetine	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.
Placebo Group	Paroxetine	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.

Primary Outcome Measures

Name	Time	Method
Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score	Baseline, End of Study (Up to 52 Weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM)	Baseline, 3 Months Post Treatment	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.