Posttraumatic Stress Disorder
Conditions
Keywords
PTSD, anxiety disorders, trauma
Brief summary
This randomized controlled trial evaluates efficacy of combined prolonged exposure (PE) and the selective serotonin reuptake inhibitor (SSRI) paroxetine in the treatment of survivors of the World Trade Center (WTC) attacks.
Detailed description
Selective serotonin reuptake inhibitor (SSRI) medication is often recommended in combination with cognitive behavioral therapies for PTSD, but combined initial treatment of PTSD has not been studied under controlled conditions. Also, there are few studies of either treatment in survivors of terrorism. This randomized controlled trial evaluates efficacy of combined prolonged exposure (PE) and the SSRI paroxetine in the treatment of survivors of the World Trade Center (WTC) attacks.
Interventions
DRUGParoxetine
Paroxetine (controlled release) 12.5-50 milligrams (mg) daily for 22 weeks
BEHAVIORALProlonged Exposure Therapy
Weekly for 10 weeks
Sponsors
National Institute of Mental Health (NIMH)
Research Foundation for Mental Hygiene, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Posttraumatic Stress Disorder, chronic, related to World Trade Center Attacks * Age 18-70 * CAPS score greater than 45 * Willingness to consent * For women, negative pregnancy test and using adequate birth control
Exclusion criteria
* Prominent suicidal ideation * Current psychotic disorder * Unstable medical illness * Women who are pregnant or nursing mothers * Alcohol or substance use disorder in the past 3 months * History of seizure disorder * conditions that contraindicate use of paroxetine * inability to tolerate a drug free period prior to beginning the study of 4 weeks for MAOIs or fluoxetine and 2 weeks for other psychotropic drugs, except zolpidem for insomnia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Administered PTSD Scale (CAPS) | Weeks 0,5,10 | PTSD severity, minimum = 0 = no symptoms of PTSD maximum = 136 = extremely severe symptoms of PTSD |
| Number of Participants Who Met Remission Criterion | Weeks 5,10 | remission defined as: CAPS less than or equal to 20 and Clinical Global Impression (CGI)-change score=1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response at Weeks 5 and 10 | weeks 5,10 | responder status: CGI-change score of 1 or 2 1=very much improved, 2= much improved |
| Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | weeks 0,5,10 | total score at weeks 0, 5, 10 |
| Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | weeks 0,5,10 | Measures life enjoyment and satisfaction across 16 domains 16 = very poor quality of life to 80 =very good quality of life |
Countries
United States
Participant flow
Recruitment details
Recruitment dates: December, 2004 to February, 2009. Location: Anxiety Disorders research clinic.
Participants by arm
| Arm | Count |
|---|---|
| Paroxetine Paroxetine and Prolonged Exposure Therapy | 19 |
| Placebo Pill Placebo pill plus Prolonged Exposure Therapy | 18 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Treatment | Lack of Efficacy | 0 | 1 |
| Maintenance Treatment | Lost to Follow-up | 1 | 1 |
| Maintenance Treatment | Withdrawal by Subject | 1 | 0 |
| Randomized Treatment | Adverse Event | 1 | 1 |
| Randomized Treatment | Lost to Follow-up | 1 | 0 |
| Randomized Treatment | Protocol Violation | 3 | 2 |
| Randomized Treatment | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Paroxetine | Placebo Pill | 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 | 19 Participants | 18 Participants | 37 Participants |
| Region of Enrollment United States | 19 participants | 18 participants | 37 participants |
| Sex: Female, Male Female | 8 Participants | 12 Participants | 20 Participants |
| Sex: Female, Male Male | 11 Participants | 6 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 19 | 5 / 18 |
| serious Total, serious adverse events | 0 / 19 | 0 / 18 |
Outcome results
Primary
Clinician Administered PTSD Scale (CAPS)
PTSD severity, minimum = 0 = no symptoms of PTSD maximum = 136 = extremely severe symptoms of PTSD
Time frame: Weeks 0,5,10
Population: all participants who were randomized
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paroxetine | Clinician Administered PTSD Scale (CAPS) | week 0 | 72.6 units on a scale | Standard Deviation 12.9 |
| Paroxetine | Clinician Administered PTSD Scale (CAPS) | week 5 | 40.7 units on a scale | Standard Deviation 28.4 |
| Paroxetine | Clinician Administered PTSD Scale (CAPS) | week 10 | 21.5 units on a scale | Standard Deviation 19.9 |
| Placebo Pill | Clinician Administered PTSD Scale (CAPS) | week 0 | 65.4 units on a scale | Standard Deviation 12.8 |
| Placebo Pill | Clinician Administered PTSD Scale (CAPS) | week 5 | 49.0 units on a scale | Standard Deviation 23.9 |
| Placebo Pill | Clinician Administered PTSD Scale (CAPS) | week 10 | 35.6 units on a scale | Standard Deviation 31.3 |
Comparison: caps total score at weeks 5 and 10p-value: 0.0195% CI: [0.3, 0.85]Mixed Models Analysis
Comparison: rate of change in CAPS total from week 5 to week 10p-value: <0.00195% CI: [0.43, 0.74]Mixed Models Analysis
Primary
Number of Participants Who Met Remission Criterion
remission defined as: CAPS less than or equal to 20 and Clinical Global Impression (CGI)-change score=1
Time frame: Weeks 5,10
Population: all participants who were randomized, with people who dropped out counted as non-remitters
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paroxetine | Number of Participants Who Met Remission Criterion | week 5 | 2 participants |
| Paroxetine | Number of Participants Who Met Remission Criterion | week 10 | 8 participants |
| Placebo Pill | Number of Participants Who Met Remission Criterion | week 5 | 0 participants |
| Placebo Pill | Number of Participants Who Met Remission Criterion | week 10 | 3 participants |
Comparison: treatment group effect: remission rate at weeks 5 and 10p-value: 0.0395% CI: [1.23, 129]Mixed Models Analysis
Comparison: rate of change over time in remission rate from week 5 to 10p-value: 0.00795% CI: [2.44, 176]Mixed Models Analysis
Secondary
Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms
total score at weeks 0, 5, 10
Time frame: weeks 0,5,10
Population: observed data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paroxetine | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 0 | 16.9 units on a scale | Standard Deviation 4.9 |
| Paroxetine | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 5 | 11.7 units on a scale | Standard Deviation 5.9 |
| Paroxetine | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 10 | 7.7 units on a scale | Standard Deviation 3.7 |
| Placebo Pill | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 0 | 16.6 units on a scale | Standard Deviation 4.9 |
| Placebo Pill | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 5 | 11.8 units on a scale | Standard Deviation 5.6 |
| Placebo Pill | Hamilton Depression Scale 0 = no Depression Symptoms 40 = Extreme Depression Symptoms | week 10 | 11.4 units on a scale | Standard Deviation 6.7 |
Secondary
Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10
Measures life enjoyment and satisfaction across 16 domains 16 = very poor quality of life to 80 =very good quality of life
Time frame: weeks 0,5,10
Population: observed data at weeks 0, 5, and 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paroxetine | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 0 | 47.1 units on a scale | Standard Deviation 11 |
| Paroxetine | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 5 | 55.5 units on a scale | Standard Deviation 13.4 |
| Paroxetine | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 10 | 67.9 units on a scale | Standard Deviation 12.7 |
| Placebo Pill | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 0 | 45.4 units on a scale | Standard Deviation 18.5 |
| Placebo Pill | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 5 | 59.4 units on a scale | Standard Deviation 17.6 |
| Placebo Pill | Quality of Life Enjoyment and Satisfaction Scale Total Score at Week 0,5,10 | week 10 | 54.8 units on a scale | Standard Deviation 22.3 |
Secondary
Treatment Response at Weeks 5 and 10
responder status: CGI-change score of 1 or 2 1=very much improved, 2= much improved
Time frame: weeks 5,10
Population: all subjects randomized with dropouts carried forward as nonresponders
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paroxetine | Treatment Response at Weeks 5 and 10 | week 5 | 6 participants |
| Paroxetine | Treatment Response at Weeks 5 and 10 | week 10 | 12 participants |
| Placebo Pill | Treatment Response at Weeks 5 and 10 | week 5 | 6 participants |
| Placebo Pill | Treatment Response at Weeks 5 and 10 | week 10 | 7 participants |