PTSD
Conditions
Keywords
PTSD, childhood abuse
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
Interventions
DRUGPlacebo
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.
DRUGParoxetine
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.
Participants will undergo positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water with exposure to traumatic scripts
Sponsors
National Institute of Mental Health (NIMH)
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Emory Clinic and Emory University Hospitals from September 2006 to November 2013.
Pre-assignment details
Of the 91 participants who were consented, 7 were excluded due to not meeting screening criteria.
Participants by arm
| Arm | Count |
|---|---|
| Paroxetine Group Women who have experienced early childhood abuse and have PTSD were randomized in a double blind fashion to receive paroxetine for a three month period followed by an open label phase of three months.
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks. | 15 |
| Placebo Group Women who have experienced early childhood abuse and have PTSD were 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: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
Paroxetine: Following a three month double blind phase, subjects were treated with open label paroxetine at a variable dosage of 10-40 mg to reach individual therapeutic levels for three months.
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks. | 13 |
| PTSD Negative Women who have experienced early childhood abuse and do not have PTSD served as a control group and completed baseline assessments
Positron Emission Tomography (PET) Imaging: Participants underwent positron emission tomography (PET) imaging of the brain with O-15 radiolabelled water while completing memory tasks. | 56 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 | 6 |
| Overall Study | Protocol Violation | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 33 |
Baseline characteristics
| Characteristic | Paroxetine Group | Placebo Group | PTSD Negative | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 13 Participants | 56 Participants | 84 Participants |
| Region of Enrollment United States | 15 participants | 13 participants | 56 participants | 84 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 56 Participants | 84 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 13 | 0 / 56 |
| other Total, other adverse events | 0 / 15 | 0 / 13 | 0 / 56 |
| serious Total, serious adverse events | 0 / 15 | 0 / 13 | 0 / 56 |
Outcome results
Primary
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.
Time frame: Baseline, End of Study (Up to 52 Weeks)
Population: Data for participants who completed all study visits were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paroxetine Group | Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score | End of Study (Up to 52 Weeks) | 20 units on a scale | Standard Deviation 10 |
| Paroxetine Group | Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score | Baseline | 31 units on a scale | Standard Deviation 10 |
| Placebo Group | Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score | Baseline | 30 units on a scale | Standard Deviation 5 |
| Placebo Group | Mean Clinical Administered PTSD Scale for DSM-IV (CAPS) Score | End of Study (Up to 52 Weeks) | 25 units on a scale | Standard Deviation 6 |
Secondary
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.
Time frame: Baseline, 3 Months Post Treatment
Population: Statistical analyses yielded image data sets in which the values assigned to individual voxels correspond to the t-statistic of the difference in brain blood flow between conditions. Statistical images were displayed with values of z score units.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paroxetine Group | Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM) | 22 z-scores |
| Placebo Group | Change in Brain Blood Flow Assessed by Statistical Parametric Mapping (SPM) | 2.68 z-scores |