Posttraumatic Stress Disorder
Conditions
Keywords
combat-related PTSD, Posttraumatic stress disorder, prolonged exposure therapy, sertraline, military, veterans, VA hospital, mental illness
Brief summary
The current research study aims to compare the effectiveness of two proven treatments for posttraumatic stress disorder (PTSD): Prolonged Exposure (PE), sertraline, and their combination. In addition, the investigators are examining predictors of response to these two treatments and how PTSD symptoms, thoughts, and biological factors may be changed by such treatments. Biological mechanisms of change are also examined including emotion processing and regulation in fMRI, HPA axis function, and genetics and genomics. In addition, the investigators will examine acceptability of each treatment and reasons for ending treatment.
Interventions
DRUGSertraline
Initial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8.
BEHAVIORALProlonged Exposure Therapy
up to 13 sessions of prolonged exposure
Sponsors
U.S. Army Medical Research and Development Command
VA Ann Arbor Healthcare System
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patient is an Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combat veteran with chronic posttraumatic stress disorder (PTSD) or significant PTSD symptoms (Clinician Administered Posttraumatic Stress Disorder Scale \[CAPS\] \>= 50) of at least 3 months duration
Exclusion criteria
* Current, imminent risk of suicide (as indicated on C-SSRS) * Active psychosis * Alcohol or substance dependence in the past 8 weeks * Unable to attend regular appointments * Prior intolerance or failure of adequate trial of prolonged exposure (PE) or sertraline (SERT) (defined as at least 2 months of SERT at least 100mg/day) * Medical illness likely to result in hospitalization or for which treatments are contraindicated (based on lab results, medical history and physical exam) * Serious cognitive impairment (as evidenced by cognitive impairment felt likely to interfere with the ability to participate meaningfully in the study) * Concurrent antidepressants or antipsychotics * Pregnant females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) | 24 weeks | Total Score; Range 0-136 with increasing PTSD severity as scores increase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient Health Questionnaire-15 | 24 weeks | PHQ-15; measures somatization and ranges from 0 to 30 and 0-9 is considered minimal/low, 10-14 is moderate, and 15-30 is severe |
Countries
United States
Participant flow
Pre-assignment details
Patients were informed of assignment at first treatment visit. Only those randomized patients who started treatment are included below (16 patients never started treatment. They did not know condition assignment.).
Participants by arm
| Arm | Count |
|---|---|
| Sertraline + Enhanced Medication Management (SERT/EMM) 24 weeks of sertraline + enhanced medication management
Sertraline: Initial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8. | 71 |
| Prolonged Exposure + Sertraline (PE/SERT) Up to 13 sessions of prolonged exposure therapy + 24 weeks of sertraline
Sertraline: Initial baseline dose of 25 mg/day. Clinician will attempt to titrate patients to at least 100 mg/day and up to 200 mg/day if tolerated by week 8.
Prolonged Exposure Therapy: up to 13 sessions of prolonged exposure | 69 |
| Prolonged Exposure + Placebo (PE/PLB) Up to 13 sessions of prolonged exposure therapy + 24 weeks of placebo
Prolonged Exposure Therapy: up to 13 sessions of prolonged exposure | 67 |
| Total | 207 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study 52 Weeks | Lost to Follow-up | 16 | 15 | 15 |
| Overall Study 52 Weeks | Physician Decision | 1 | 0 | 2 |
| Overall Study 52 Weeks | Withdrawal by Subject | 4 | 5 | 10 |
| Treatment Phase | Lost to Follow-up | 0 | 1 | 2 |
| Treatment Phase | Physician Decision | 6 | 3 | 3 |
| Treatment Phase | Withdrawal by Subject | 13 | 28 | 31 |
Baseline characteristics
| Characteristic | Sertraline + Enhanced Medication Management (SERT/EMM) | Prolonged Exposure + Sertraline (PE/SERT) | Prolonged Exposure + Placebo (PE/PLB) | Total |
|---|---|---|---|---|
| Age, Continuous | 33.7 years STANDARD_DEVIATION 8.2 | 35.1 years STANDARD_DEVIATION 8.5 | 34.7 years STANDARD_DEVIATION 8.3 | 34.5 years STANDARD_DEVIATION 8.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 10 Participants | 7 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 59 Participants | 60 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race African American | 20 Participants | 22 Participants | 20 Participants | 62 Participants |
| Race/Ethnicity, Customized Race Other | 8 Participants | 7 Participants | 11 Participants | 26 Participants |
| Race/Ethnicity, Customized Race White | 43 Participants | 40 Participants | 36 Participants | 119 Participants |
| Region of Enrollment United States | 71 Participants | 69 Participants | 67 Participants | 207 Participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 8 Participants | 27 Participants |
| Sex: Female, Male Male | 66 Participants | 55 Participants | 59 Participants | 180 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 71 | 0 / 69 | 0 / 67 |
| other Total, other adverse events | 69 / 71 | 61 / 69 | 46 / 67 |
| serious Total, serious adverse events | 0 / 71 | 5 / 69 | 3 / 67 |
Outcome results
Primary
Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS)
Total Score; Range 0-136 with increasing PTSD severity as scores increase
Time frame: 24 weeks
Population: All randomized patients who received treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline + Enhanced Medication Management (SERT/EMM) | Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) | 41.7 Scores on a scale | Standard Deviation 25.7 |
| Prolonged Exposure + Sertraline (PE/SERT) | Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) | 43.3 Scores on a scale | Standard Deviation 27.2 |
| Prolonged Exposure + Placebo (PE/PLB) | Posttraumatic Stress Disorder (PTSD) Symptoms as Measured by the Clinician Administered Posttraumatic Stress Disorder Scale (CAPS) | 51.5 Scores on a scale | Standard Deviation 25.3 |
Secondary
Patient Health Questionnaire-15
PHQ-15; measures somatization and ranges from 0 to 30 and 0-9 is considered minimal/low, 10-14 is moderate, and 15-30 is severe
Time frame: 24 weeks
Population: All Randomized patients who received treatment and had the measure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline + Enhanced Medication Management (SERT/EMM) | Patient Health Questionnaire-15 | 8.6 Scores on a scale | Standard Deviation 5.7 |
| Prolonged Exposure + Sertraline (PE/SERT) | Patient Health Questionnaire-15 | 9.8 Scores on a scale | Standard Deviation 5.7 |
| Prolonged Exposure + Placebo (PE/PLB) | Patient Health Questionnaire-15 | 10.5 Scores on a scale | Standard Deviation 5.1 |