Posttraumatic Stress Disorder
Conditions
Keywords
Posttraumatic Stress Disorder, Meditation, Present Centered Group Therapy, mindfulness, MBSR, complementary alternative medicine
Brief summary
Currently, veterans with posttraumatic stress disorder (PTSD) are typically treated with antidepressants which have limited efficacy and yield extremely low remission rates. New and improved treatments are sorely needed, especially in light of the inadequate evidence to support the efficacy of most pharmacologic and most psychotherapy treatments for PTSD. Complementary and Alternative Medicine practices, such as meditation, may fill this void. Several other illnesses often found in association with PTSD, such as chronic pain, anxiety, and depression, have shown positive response to meditation, specifically Mindfulness Based Stress Reduction (MBSR). MBSR is manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes. MBSR is well tolerated, already well disseminated. MBSR has been shown to be effective in reducing conditions that are commonly associated with PTSD, including pain, depression, anxiety and panic, and insomnia. The investigators are conducting a multisite study of Mindfulness Based Stress Reduction (MBSR) compared to Present Centered Group Therapy (PCGT) for the treatment of PTSD. The primary aim of this study will be to determine how well the MBSR form of meditation, i.e. MBSR, works to treat symptoms of PTSD in veterans compared to PCGT. The investigators will evaluate the effects of treatment on levels of mindfulness, depression, PTSD symptom clusters, and response rates. The investigators will evaluate veterans' satisfaction and acceptability of the MBSR intervention. Additionally, biomarkers will be utilized to aid in our understanding of the pathophysiology of meditation and explore the relationship between treatment outcome and neuroimmune response.
Detailed description
This study is a prospective, randomized (1:1), controlled multisite study of MBSR in 180 veterans with PTSD. The investigators will compare the clinical outcomes of MBSR to a credible group therapy control condition called Present Centered Group Therapy (PCGT). The investigators will to evaluate the efficacy of MBSR in the treatment of PTSD, as defined by the Clinician Administered PTSD Scale (CAPS), a gold standard measure that is clinically relevant to PTSD. The CAPS will be rated by a trained assessor who is blind to the whether or not the participant receives the MBSR or PCGT intervention. Secondarily, the investigators will evaluate the effects of MBSR on mindfulness, depression, PTSD symptom clusters, rates of response and evaluate the safety and tolerability of MBRS. The investigators will also explore the subjects' acceptance of and satisfaction with MBSR, whether or not the subjects' treatment preference influences outcome; the stress-immunological-biomarkers as they relate to treatment outcome; and the durability of therapeutic effects of MBSR in the treatment of PTSD. Study Design Overview: Male and female subjects from Active Duty, Reserves, National Guard and/or Veterans with a diagnosis of PTSD will be prospectively randomized 1:1 to receive either MBSR Group therapy or Present Centered Therapy (PCGT) Group (control) for 8 weeks. A cluster of at least 12 participants will be randomized individually to either MBRS or PCGT group therapies, which results in at least 6 participants in each intervention group. A total of 30 groups (15 MBSR Groups and 15 PCGT Groups) are anticipated across three clinical research sites involving at least three different MBSR and three different PCGT instructors/therapists. Outcome assessments (single-blind CAPS and self-report measures) will be obtained at baseline, week 3, week 6, and week 9 (primary endpoint). These assessments will be repeated post-acute treatment at week 16 as an exploratory measure of short-term durability effects.
Interventions
BEHAVIORALMindfulness Based Stress Reduction
MBSR is a manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes.
BEHAVIORALPresent Centered Group Therapy
The comparison control group will be PCGT, which was initially developed for use as a control group in a VA multi-site study that tested the effects of Trauma-Focused Group Therapy. Correspondingly, PCGT serves as a credible control for the nonspecific effects of a group-based intervention (i.e. controls for time, attention, expectation of recovery, and recognition of the illness).
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization form. * \> or = 18 years of age. * Diagnosis of PTSD (DSM-IV-TR criteria; confirmed by MINI and CAPS). * Total CAPS score \> 45 for the week prior to randomization. * No substance use disorders (except for nicotine, caffeine) for 2 weeks prior to randomization (Able to Travel to the clinical sites in Tuscaloosa, AL, Atlanta, GA, or Charleston, SC
Exclusion criteria
* Lifetime history of bipolar I, schizophrenia, schizoaffective or cognitive disorders (MINI) * Actively considering plans of suicide or homicide (assessed by clinical interview) * Psychotic symptoms that in the investigator's opinion impair the subject's ability to give informed consent and participate in the study interventions * Severe cognitive disorder (Dementia, severe Traumatic Brain Injury) * Clinically significant unstable or severe medical condition that would contraindicate study participation or expose them to an undue risk of a significant adverse event. * In regard to vulnerable patient populations, persons with dementia, minors (\<age 19), the elderly (\>age 65), prisoners and the terminally ill are excluded. * Individuals with significant psychotic or dissociative symptoms or severe personality disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinician Administered PTSD Scale | Baseline to week 9 | Clinician Administered PTSD Scale (CAPS) is a 17-item standard rating scale that measures PTSD severity with scores ranging from 0-136 (higher score = more severe). Scores of frequency and intensity are summed for the 17-items to yield the total CAPS score. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Five Facet Mindfulness Questionnaire (FFMQ) | Baseline to week 9 | Five Facet Mindfulness Questionnaire (FFMQ) is used to evaluate the effects of MBSR vs. PCGT on mindfulness (S1). The FFMQ is a 39-item self-report instrument that assesses the general tendency to be mindful in daily life through 5 facets: observing, describing, acting with awareness, non-judging of inner experience, non-reactivity to inner experience. Increases in FFMQ mediate improvements in well being in observational studies of MBSR. Each item is rated 1 to 5 (never or very rarely true to very often or always true). Some of the items are reverse scored (R). Scoring Information: Observe items:1, 6, 11, 15, 20, 26, 31, 36; Describe items: 2, 7, 12R, 16R, 22R, 27, 32, 37; Act with Awareness items: 5R, 8R, 13R, 18R, 23R, 28R, 34R, 38R; Nonjudge items: 3R, 10R, 14R, 17R, 25R, 30R, 35R, 39R; Nonreact items: 4, 9, 19, 21, 24, 29, 33. Total all subscales for score (higher score = greater degree of mindfulness). Score range 39-195 with higher=more mindfulness. |
| Change From Baseline in Patient Health Questionnaire (PHQ-9) | Baseline to week 9 | Patient Health Questionnaire (PHQ-9) is a brief 9-item measure of depressive symptoms that has established reliability and validity in community and clinical populations. All items are summed for total score ranging from 0 to 27 (higher score = more severe depression). |
| Change From Baseline in CAPS B Subscale | Baseline to week 9 | Clinician Administered PTSD Scale (CAPS) B subscale measures the re-experiencing cluster (i.e. B criterion) of PTSD symptoms and includes the first 5 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD). |
| Change From Baseline in PTSD Checklist (PCL) | Baseline to week 9 | PTSD Checklist (PCL) is a 17-item self-report scale intended to measure PTSD symptom severity. The PCL has demonstrated excellent internal consistency (alpha = .94-.97), and test-retest reliability over 2 to 3 days was .96 for Vietnam veterans. Respondents rate each item from 1 (not at all) to 5 (extremely) to indicate the degree to which they have been bothered by that particular symptom over the past month. Thus, total possible scores (items summed) range from 17 to 85 (higher score is more severe). A cut-off score of 50 indicates a probable diagnosis of PTSD. |
| Change From Baseline in CAPS D Subscale | Baseline to week 9 | Clinician Administered PTSD Scale (CAPS) D subscale measures the hyperarousal cluster (i.e. D criterion) of PTSD symptoms and includes the items 13 - 17 of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD). |
| PTSD Response | Baseline to week 9 | Greater than or equal to 30% improvement on PTSD CAPS scale |
| PTSD Remission | Week 9 | Total CAPS score of less than or equal to 45 at week 9 (single observation point) |
| Change From Baseline in CAPS C Subscale | Baseline to week 9 | Clinician Administered PTSD Scale (CAPS) C subscale measures the avoidance and emotional numbing cluster (i.e. C criterion) of PTSD symptoms and includes the items 6 - 12 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 56 (higher score = more severe PTSD). |
Countries
United States
Participant flow
Pre-assignment details
254 participants signed informed consent; 214 participants were randomized; and 191 randomized participants attended at least one MBSR or PCGT session and were included in the modified intent-to-treat analysis for which results are displayed.
Participants by arm
| Arm | Count |
|---|---|
| Mindfulness Based Stress Reduction Mindfulness Based Stress Reduction (MBSR) is a manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes.
Mindfulness Based Stress Reduction: MBSR is a manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes. | 96 |
| Present Centered Group Therapy Present Centered Group Therapy (PCGT) serves as a credible control for the nonspecific effects of a group-based intervention (i.e. controls for time, attention, expectation of recovery, and recognition of the illness).
Present Centered Group Therapy: The comparison control group will be PCGT, which was initially developed for use as a control group in a VA multi-site study that tested the effects of Trauma-Focused Group Therapy. Correspondingly, PCGT serves as a credible control for the nonspecific effects of a group-based intervention (i.e. controls for time, attention, expectation of recovery, and recognition of the illness). | 95 |
| Total | 191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | incarcerated | 0 | 1 |
| Overall Study | Lost to Follow-up | 14 | 8 |
| Overall Study | New job | 0 | 2 |
| Overall Study | no show for week 9 assessments | 6 | 4 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Relocated | 2 | 0 |
| Overall Study | should not have been randomized | 1 | 0 |
| Overall Study | substantial noncompliance | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 0 |
Baseline characteristics
| Characteristic | Mindfulness Based Stress Reduction | Present Centered Group Therapy | Total |
|---|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 11 | 51 years STANDARD_DEVIATION 8.3 | 51 years STANDARD_DEVIATION 11 |
| CAPS Total | 84.3 units on a scale STANDARD_DEVIATION 19.5 | 80.7 units on a scale STANDARD_DEVIATION 16.7 | 83 units on a scale STANDARD_DEVIATION 18.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 63 Participants | 59 Participants | 122 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 30 Participants | 31 Participants | 61 Participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 80 Participants | 80 Participants | 160 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 96 | 0 / 95 |
| serious Total, serious adverse events | 4 / 96 | 4 / 95 |
Outcome results
Primary
Change From Baseline in Clinician Administered PTSD Scale
Clinician Administered PTSD Scale (CAPS) is a 17-item standard rating scale that measures PTSD severity with scores ranging from 0-136 (higher score = more severe). Scores of frequency and intensity are summed for the 17-items to yield the total CAPS score.
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in Clinician Administered PTSD Scale | -22.4 units on a scale | Standard Deviation 27 |
| Present Centered Group Therapy | Change From Baseline in Clinician Administered PTSD Scale | -15.9 units on a scale | Standard Deviation 22.9 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks. Data structure involved repeated measures over time nested within participant, who in turn, was nested within a therapy group. Models included a random intercept, a random slope, and fixed effects for treatment condition, time, and the stratification variable (site). Rejection of the null hypothesis of no treatment effect if this interaction was statistically significant (two-tailed α = .05).p-value: 0.5Regression, Linear
Secondary
Change From Baseline in CAPS B Subscale
Clinician Administered PTSD Scale (CAPS) B subscale measures the re-experiencing cluster (i.e. B criterion) of PTSD symptoms and includes the first 5 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD).
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in CAPS B Subscale | -7.7 units on a scale | Standard Deviation 10.4 |
| Present Centered Group Therapy | Change From Baseline in CAPS B Subscale | -6.2 units on a scale | Standard Deviation 8.9 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks.p-value: 0.8Regression, Linear
Secondary
Change From Baseline in CAPS C Subscale
Clinician Administered PTSD Scale (CAPS) C subscale measures the avoidance and emotional numbing cluster (i.e. C criterion) of PTSD symptoms and includes the items 6 - 12 items of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 56 (higher score = more severe PTSD).
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in CAPS C Subscale | -8.8 units on a scale | Standard Deviation 12.6 |
| Present Centered Group Therapy | Change From Baseline in CAPS C Subscale | -6.8 units on a scale | Standard Deviation 10.8 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks.p-value: 0.4Regression, Linear
Secondary
Change From Baseline in CAPS D Subscale
Clinician Administered PTSD Scale (CAPS) D subscale measures the hyperarousal cluster (i.e. D criterion) of PTSD symptoms and includes the items 13 - 17 of the CAPS, which is a clinician-administered assessment of posttraumatic stress disorder (PTSD) symptoms. Frequency and intensity scores for each item is summed for a range of 0 to 40 (higher score = more severe PTSD).
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in CAPS D Subscale | -5.9 units on a scale | Standard Deviation 9.3 |
| Present Centered Group Therapy | Change From Baseline in CAPS D Subscale | -3 units on a scale | Standard Deviation 7.6 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks.p-value: 0.35Regression, Linear
Secondary
Change From Baseline in Five Facet Mindfulness Questionnaire (FFMQ)
Five Facet Mindfulness Questionnaire (FFMQ) is used to evaluate the effects of MBSR vs. PCGT on mindfulness (S1). The FFMQ is a 39-item self-report instrument that assesses the general tendency to be mindful in daily life through 5 facets: observing, describing, acting with awareness, non-judging of inner experience, non-reactivity to inner experience. Increases in FFMQ mediate improvements in well being in observational studies of MBSR. Each item is rated 1 to 5 (never or very rarely true to very often or always true). Some of the items are reverse scored (R). Scoring Information: Observe items:1, 6, 11, 15, 20, 26, 31, 36; Describe items: 2, 7, 12R, 16R, 22R, 27, 32, 37; Act with Awareness items: 5R, 8R, 13R, 18R, 23R, 28R, 34R, 38R; Nonjudge items: 3R, 10R, 14R, 17R, 25R, 30R, 35R, 39R; Nonreact items: 4, 9, 19, 21, 24, 29, 33. Total all subscales for score (higher score = greater degree of mindfulness). Score range 39-195 with higher=more mindfulness.
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in Five Facet Mindfulness Questionnaire (FFMQ) | 5.2 units on a scale | Standard Deviation 16.6 |
| Present Centered Group Therapy | Change From Baseline in Five Facet Mindfulness Questionnaire (FFMQ) | 2.1 units on a scale | Standard Deviation 13.2 |
Secondary
Change From Baseline in Patient Health Questionnaire (PHQ-9)
Patient Health Questionnaire (PHQ-9) is a brief 9-item measure of depressive symptoms that has established reliability and validity in community and clinical populations. All items are summed for total score ranging from 0 to 27 (higher score = more severe depression).
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in Patient Health Questionnaire (PHQ-9) | -3.2 units on a scale | Standard Deviation 6.6 |
| Present Centered Group Therapy | Change From Baseline in Patient Health Questionnaire (PHQ-9) | -1.6 units on a scale | Standard Deviation 6.3 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks.p-value: 0.4Regression, Linear
Secondary
Change From Baseline in PTSD Checklist (PCL)
PTSD Checklist (PCL) is a 17-item self-report scale intended to measure PTSD symptom severity. The PCL has demonstrated excellent internal consistency (alpha = .94-.97), and test-retest reliability over 2 to 3 days was .96 for Vietnam veterans. Respondents rate each item from 1 (not at all) to 5 (extremely) to indicate the degree to which they have been bothered by that particular symptom over the past month. Thus, total possible scores (items summed) range from 17 to 85 (higher score is more severe). A cut-off score of 50 indicates a probable diagnosis of PTSD.
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mindfulness Based Stress Reduction | Change From Baseline in PTSD Checklist (PCL) | -8.6 units on a scale | Standard Deviation 15.8 |
| Present Centered Group Therapy | Change From Baseline in PTSD Checklist (PCL) | -6.7 units on a scale | Standard Deviation 12 |
Comparison: Three-level mixed-effects linear regression analysis comparing MBSR and PCGT groups over 9 weeks.p-value: 0.57Regression, Linear
Secondary
PTSD Remission
Total CAPS score of less than or equal to 45 at week 9 (single observation point)
Time frame: Week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mindfulness Based Stress Reduction | PTSD Remission | 30.7 percentage of participants |
| Present Centered Group Therapy | PTSD Remission | 27.3 percentage of participants |
Comparison: Mixed effects logistic regression analysis.p-value: 0.7Regression, Logistic
Secondary
PTSD Response
Greater than or equal to 30% improvement on PTSD CAPS scale
Time frame: Baseline to week 9
Population: All participants who were randomized and attended at least one intervention session.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mindfulness Based Stress Reduction | PTSD Response | 45.2 percentage of participants |
| Present Centered Group Therapy | PTSD Response | 37.7 percentage of participants |
Comparison: Mixed effects logistic regression analysis.p-value: 0.3Regression, Logistic