Stress Disorders, Post-Traumatic
Conditions
Keywords
PTSD, Paroxetine, Subthreshold
Brief summary
The purpose of this study is: 1) To document the effectiveness and tolerability of paroxetine for the treatment of subthreshold posttraumatic stress disorder (PTSD) in veterans in the early post-deployment period; and 2) To determine the potential efficacy of paroxetine in preventing the progression of anxiety symptoms to PTSD and other anxiety disorders, and improving overall veteran function.
Detailed description
See brief summary
Interventions
DRUGParoxetine
Paroxetine 10 mg-40 mg or placebo; flexible dosing; 12-week duration.
DRUGPlacebo
Placebo: same as paroxetine (active comparator)
Sponsors
Durham VA Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Veterans 18-55 years of age 2. Diagnosis of subthreshold PTSD (at least one symptom in PTSD symptom clusters B, C, and D by structured interview; with or without functional impairment exposure to war zone stressors) 3. Written informed consent; and 4. A negative serum pregnancy test for women of childbearing potential.
Exclusion criteria
1. Lifetime history of DSM-IV diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition 2. History of substance dependence within the last 3 months 3. Significant suicide risk or serious suicide attempt within the last year 4. Clinically significant medical condition or laboratory or EKG abnormality 5. Women of childbearing potential who are unwilling to practice an acceptable method of contraception 6. Subjects needing concurrent use of psychiatric medications 7. History of hypersensitivity to paroxetine 8. HADS depression subscale score \> 12 9. Failure to respond to an adequate trial of paroxetine (20 mg/day x 8 wks).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician Administered PTSD Scale (CAPS) Scores | Change in Scores (12 weeks-Baseline) | Mean change scores in posttraumatic stress disorder symptoms. Raw scores may range from 0 (no symptoms) to 136 (severe symptoms; score of 136 is based on the first 17 CAPS items administered). A reduced CAPS score indicates a reduction in (improvement) PTSD symptoms, while an increase in CAPS score indicates an increase (worsening) in PTSD symptoms. The outcome measure is the change in scores before and after treatment. That is, the baseline and at 12 weeks difference scores. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Short PTSD Rating Interview Scores | Change in Scores (12 weeks-Baseline) | The SPRINT contains 8 questions which are rated on a 0-4 scale (0=not at all; 4=very much). The total score is computed from summing questions #1-8 (range=0-32). The higher the total score, the worse the symptoms. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores. |
| Change in Connor Davidson Resilience Scale Scores | Change in Scores (12 Weeks-Baseline) | This scale measures resilience. Range of scores (0-100). A score of 0 is suggestive of no resilience, a score of 100 is suggestive of high level of resilience. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores. |
| Change in Hospital Anxiety and Depression Scale Scores | Change in Scores (12 Weeks-Baseline) | The total HADS score is presented, which is regarded as a global measure of psychological distress. The total score ranges from 0-42. Each individual question is rated on a 4 point scale (0=absent to 3 =extreme presence). The higher the score, the greater level of psychological distress. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores. |
Countries
United States
Participant flow
Recruitment details
Patient enrollment at the Durham VA Medical Center occurred from February 2006 until July 2008.
Participants by arm
| Arm | Count |
|---|---|
| Paroxetine Week 0: Randomization to paroxetine 10 mg per day for 1 week, Week 1: Paroxetine 10-20 mg/day for 2 weeks (increase to 20 mg/day if tolerating 10 mg/day dose without side effects).
Week 3: Paroxetine 10-20 mg per day for 2 weeks (increase to 20 mg/day, if tolerating 10 mg/day without side effects and if not already taking 20 mg/day).
Week 5: Paroxetine 10-30 mg per day for 3 weeks (increase to 30 mg/day if receiving 20 mg/day dose and tolerating without side effects).
Week 8: Paroxetine 10-40 mg per day for 4 weeks (increase to 40 mg/day if receiving 30 mg/day and tolerating without side effects).
Week 12: Final study visit (no study medication dispensed). | 5 |
| Placebo Week 0: Randomization to placebo for 1 week. Week 1: Placebo for 2 weeks (10-20mg). Week 3: Placebo for 2 weeks (10-20mg). Week 5: Placebo for 3 weeks (10-30mg). Week 8: Placebo for 4 weeks (10-40mg). Week 12: Final study visit (no study medication dispensed). | 7 |
| Total | 12 |
Baseline characteristics
| Characteristic | Placebo | Paroxetine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 5 Participants | 12 Participants |
| Age, Continuous | 35.9 years STANDARD_DEVIATION 9.69 | 39.3 years STANDARD_DEVIATION 4.73 | 37.3 years STANDARD_DEVIATION 7.9 |
| Region of Enrollment United States | 7 participants | 5 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 5 | 5 / 7 |
| serious Total, serious adverse events | 0 / 5 | 0 / 7 |
Outcome results
Primary
Change in Clinician Administered PTSD Scale (CAPS) Scores
Mean change scores in posttraumatic stress disorder symptoms. Raw scores may range from 0 (no symptoms) to 136 (severe symptoms; score of 136 is based on the first 17 CAPS items administered). A reduced CAPS score indicates a reduction in (improvement) PTSD symptoms, while an increase in CAPS score indicates an increase (worsening) in PTSD symptoms. The outcome measure is the change in scores before and after treatment. That is, the baseline and at 12 weeks difference scores.
Time frame: Change in Scores (12 weeks-Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine | Change in Clinician Administered PTSD Scale (CAPS) Scores | -3.40 Units on a scale | Standard Deviation 7.37 |
| Placebo | Change in Clinician Administered PTSD Scale (CAPS) Scores | -5.00 Units on a scale | Standard Deviation 6.78 |
p-value: 0.7054t-test, 2 sided
Secondary
Change in Connor Davidson Resilience Scale Scores
This scale measures resilience. Range of scores (0-100). A score of 0 is suggestive of no resilience, a score of 100 is suggestive of high level of resilience. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Time frame: Change in Scores (12 Weeks-Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine | Change in Connor Davidson Resilience Scale Scores | -0.80 units on a scale | Standard Deviation 11.67 |
| Placebo | Change in Connor Davidson Resilience Scale Scores | -1.29 units on a scale | Standard Deviation 9.86 |
p-value: 0.7443t-test, 2 sided
Secondary
Change in Hospital Anxiety and Depression Scale Scores
The total HADS score is presented, which is regarded as a global measure of psychological distress. The total score ranges from 0-42. Each individual question is rated on a 4 point scale (0=absent to 3 =extreme presence). The higher the score, the greater level of psychological distress. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Time frame: Change in Scores (12 Weeks-Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine | Change in Hospital Anxiety and Depression Scale Scores | -3.40 units on a scale | Standard Deviation 2.7 |
| Placebo | Change in Hospital Anxiety and Depression Scale Scores | -0.17 units on a scale | Standard Deviation 1.8 |
p-value: 0.065t-test, 2 sided
Secondary
Change in Short PTSD Rating Interview Scores
The SPRINT contains 8 questions which are rated on a 0-4 scale (0=not at all; 4=very much). The total score is computed from summing questions #1-8 (range=0-32). The higher the total score, the worse the symptoms. The outcome measure is the change in scores before and after treatment. That is, the baseline and Visit 6 difference scores.
Time frame: Change in Scores (12 weeks-Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paroxetine | Change in Short PTSD Rating Interview Scores | -3.80 units on a scale | Standard Deviation 6.14 |
| Placebo | Change in Short PTSD Rating Interview Scores | -2.00 units on a scale | Standard Deviation 1.15 |
p-value: 0.4583t-test, 2 sided