Post-traumatic Stress Disorder (PTSD)
Conditions
Keywords
Post-traumatic stress disorder, Repetitive transcranial magnetic stimulation, Civilians, Neurostimulation, Dorsolateral prefrontal cortex
Brief summary
The purpose of this study is to assess the effects of repetitive transcranial magnetic stimulation (rTMS) in civilian patients with a confirmed diagnosis of post-traumatic stress disorder (PTSD). This research study will determine whether low-frequency (1 Hertz \[Hz\]) or high-frequency (10 Hz) rTMS over the right dorsolateral prefrontal cortex (DLPFC) has an effect on symptoms of PTSD compared to sham rTMS treatment.
Interventions
DEVICErTMS
Magstim Super Rapid-2
Sponsors
Vancouver Coastal Health
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* primary diagnosis of PTSD as determined by a structured interview using the Mini International Neuropsychiatric Interview (MINI) * no change in psychotropic medications within 4 weeks before the start of rTMS * age \> 19 years and \< 70 years * competency to give informed consent
Exclusion criteria
* any non-fixed metal object or implant (including cochlear implants) in brain, skull, scalp, or neck within 30 cm of the magnetic rTMS coil * implantable devices, including cardiac pacemakers and defibrillators * other contraindications to rTMS, including history of seizures (except childhood febrile seizures) or recent and unexplained syncope, first-degree relative with a history of epilepsy, treatment with a medication known to substantially decrease the seizure threshold, or pregnancy * psychiatric diagnoses of psychosis or psychotic disorder (including psychotic depression), bipolar type I disorder, or organic mental disorders * substance abuse/dependence within the past 3 months * active suicidal risk as judged by the clinician * borderline or antisocial personality disorder * acute medical illness, including cancer * any significant central nervous system disorder, such as brain mass, stroke, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) | Endpoint (treatment end) (Week 2). | The Clinician-Administered PTSD Scale-IV (CAPS-IV) is a semi-structured instrument that assesses the intensity, frequency, and severity of PTSD symptoms. It consists of 17 symptom items, each rated on a 0-4 scale for frequency and a 0-4 scale for intensity, with higher scores indicating greater frequency/intensity. The frequency and intensity scores are then summed to yield a total item severity score (range 0-8). The minimum score of the overall scale is 0 and maximum is 17 items \* maximum severity score of 8 = 136 (higher scores indicating more severe symptoms). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PTSD Checklist for Civilians (PCL-C) | Endpoint (Week 2). | The PTSD Checklist for Civilians (PCL-C) is a standardised self-report rating scale for PTSD comprising 17 items that correspond to the DSM-V symptoms of PTSD. A total symptom severity score (range = 17-85) can be obtained by summing the scores from each of the 17 items that have response options ranging from 1 Not at all to 5 Extremely. |
| Hamilton Depression Rating Scale, 21-item Version (HDRS-21) | Endpoint (Week 2) | A clinician-rated assessment of depression symptoms consisting of 21 items rated on a scale from 0 to 4, 0 to 2, or 0 to 3, with higher scores indicating greater symptom severity in all cases. Minimum score = 0; maximum score = 53 (scores \> 23 are considered to be severe). |
| Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) | Endpoint (Week 2) | A self-report scale to assess symptoms of depression consisting of 16 items, 9 of which contribute to a summed total score (i.e., only the highest score of items 1-4, 6-9, and 15-16 are counted). Scores range from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-27, with scores \>= 21 considered very severe, 20-16 severe, 11-15 moderate, and 6-10 mild depression. |
| Beck Anxiety Inventory (BAI) | Endpoint (Week 2) | A self-report scale to assess symptoms of anxiety, consisting of 21 items scored on a scale from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-63, with scores \>= indicating potentially concerning levels of anxiety. |
| Generalized Anxiety Disorder (GAD-7) Scale | Endpoint (Week 2) | A brief self-report scale to assess symptoms of anxiety, consisting of 7 items each scored on a scale from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-21, with scores 0-4 suggesting minimal anxiety, 5-9 mild, 10-14 moderate, and 15-21 severe anxiety. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited from the psychiatry outpatient and community programs of Vancouver Coastal Health between 2014 and 2018. Some participants were recruited after attending an outpatient psychoeducation group but had not received formal group therapy. All assessments and treatments took place at Vancouver General Hospital in Vancouver, British Columbia, Canada.
Pre-assignment details
46 patients were assessed for eligibility. 15 were excluded: 7 did not meet inclusion criteria and 8 declined to participate. The remaining 31 patients were enrolled and randomized to one of three conditions.
Participants by arm
| Arm | Count |
|---|---|
| Low-frequency (1 Hz) rTMS Low-frequency active stimulation over the right dorsolateral prefrontal cortex (DLPFC) on 5 consecutive days every week for 2 weeks, for a total of 10 therapy sessions, with 37.5 minutes per session.
rTMS: Magstim Super Rapid-2 | 11 |
| High-frequency (10 Hz) rTMS High-frequency active stimulation over the right dorsolateral prefrontal cortex (DLPFC) on 5 consecutive days every week for 2 weeks, for a total of 10 therapy sessions, with 37.5 minutes per session.
rTMS: Magstim Super Rapid-2 | 9 |
| Sham rTMS Sham stimulation over the right dorsolateral prefrontal cortex (DLPFC) on 5 consecutive days every week for 2 weeks, for a total of 10 therapy sessions, with 37.5 minutes per session.
rTMS: Magstim Super Rapid-2 | 9 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Low-frequency (1 Hz) rTMS | High-frequency (10 Hz) rTMS | Sham rTMS | Total |
|---|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 13.5 | 43.5 years STANDARD_DEVIATION 12.4 | 49.5 years STANDARD_DEVIATION 6.9 | 43.7 years STANDARD_DEVIATION 12.2 |
| Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) | 72.27 units on a scale STANDARD_DEVIATION 25.34 | 69.44 units on a scale STANDARD_DEVIATION 18.29 | 55.22 units on a scale STANDARD_DEVIATION 13.17 | 66.10 units on a scale STANDARD_DEVIATION 21.35 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment Canada | 11 Participants | 9 Participants | 9 Participants | 29 Participants |
| Sex: Female, Male Female | 10 Participants | 7 Participants | 7 Participants | 24 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 1 / 11 | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV)
The Clinician-Administered PTSD Scale-IV (CAPS-IV) is a semi-structured instrument that assesses the intensity, frequency, and severity of PTSD symptoms. It consists of 17 symptom items, each rated on a 0-4 scale for frequency and a 0-4 scale for intensity, with higher scores indicating greater frequency/intensity. The frequency and intensity scores are then summed to yield a total item severity score (range 0-8). The minimum score of the overall scale is 0 and maximum is 17 items \* maximum severity score of 8 = 136 (higher scores indicating more severe symptoms).
Time frame: Endpoint (treatment end) (Week 2).
Population: Intention-to-treat population analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) | 59.80 units on a scale | Standard Deviation 35.83 |
| High-frequency (10 Hz) rTMS | Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) | 74.00 units on a scale | Standard Deviation 30.97 |
| Sham rTMS | Clinician-Administered PTSD Scale for DSM-IV (CAPS-IV) | 65.12 units on a scale | Standard Deviation 14.97 |
p-value: 0.046Mixed Models Analysis
p-value: 0.021t-test, 2 sided
p-value: 0.65t-test, 2 sided
Secondary
Beck Anxiety Inventory (BAI)
A self-report scale to assess symptoms of anxiety, consisting of 21 items scored on a scale from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-63, with scores \>= indicating potentially concerning levels of anxiety.
Time frame: Endpoint (Week 2)
Population: Intent-to-treat population analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | Beck Anxiety Inventory (BAI) | 24.70 score on a scale | Standard Deviation 18.19 |
| High-frequency (10 Hz) rTMS | Beck Anxiety Inventory (BAI) | 22.77 score on a scale | Standard Deviation 18.78 |
| Sham rTMS | Beck Anxiety Inventory (BAI) | 28.14 score on a scale | Standard Deviation 10.97 |
p-value: 0.86Mixed Models Analysis
Secondary
Generalized Anxiety Disorder (GAD-7) Scale
A brief self-report scale to assess symptoms of anxiety, consisting of 7 items each scored on a scale from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-21, with scores 0-4 suggesting minimal anxiety, 5-9 mild, 10-14 moderate, and 15-21 severe anxiety.
Time frame: Endpoint (Week 2)
Population: Intent-to-treat population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | Generalized Anxiety Disorder (GAD-7) Scale | 11.90 score on a scale | Standard Deviation 7.03 |
| High-frequency (10 Hz) rTMS | Generalized Anxiety Disorder (GAD-7) Scale | 8.50 score on a scale | Standard Deviation 8.53 |
| Sham rTMS | Generalized Anxiety Disorder (GAD-7) Scale | 11.75 score on a scale | Standard Deviation 5.62 |
p-value: 0.4Mixed Models Analysis
Secondary
Hamilton Depression Rating Scale, 21-item Version (HDRS-21)
A clinician-rated assessment of depression symptoms consisting of 21 items rated on a scale from 0 to 4, 0 to 2, or 0 to 3, with higher scores indicating greater symptom severity in all cases. Minimum score = 0; maximum score = 53 (scores \> 23 are considered to be severe).
Time frame: Endpoint (Week 2)
Population: Intent-to-treat population analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | Hamilton Depression Rating Scale, 21-item Version (HDRS-21) | 12.30 score on a scale | Standard Deviation 8.42 |
| High-frequency (10 Hz) rTMS | Hamilton Depression Rating Scale, 21-item Version (HDRS-21) | 11.22 score on a scale | Standard Deviation 7.99 |
| Sham rTMS | Hamilton Depression Rating Scale, 21-item Version (HDRS-21) | 14.44 score on a scale | Standard Deviation 3.32 |
p-value: 0.18Mixed Models Analysis
Secondary
PTSD Checklist for Civilians (PCL-C)
The PTSD Checklist for Civilians (PCL-C) is a standardised self-report rating scale for PTSD comprising 17 items that correspond to the DSM-V symptoms of PTSD. A total symptom severity score (range = 17-85) can be obtained by summing the scores from each of the 17 items that have response options ranging from 1 Not at all to 5 Extremely.
Time frame: Endpoint (Week 2).
Population: Intention-to-treat population analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | PTSD Checklist for Civilians (PCL-C) | 48.10 score on a scale | Standard Deviation 23.54 |
| High-frequency (10 Hz) rTMS | PTSD Checklist for Civilians (PCL-C) | 53.44 score on a scale | Standard Deviation 22.8 |
| Sham rTMS | PTSD Checklist for Civilians (PCL-C) | 52.14 score on a scale | Standard Deviation 10.05 |
Comparison: To test primary and secondary outcomes, we utilized intention to treat data and linear mixed models with a group random effect. Significance was set to a \< 0.05.p-value: 0.93Mixed Models Analysis
Secondary
Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR)
A self-report scale to assess symptoms of depression consisting of 16 items, 9 of which contribute to a summed total score (i.e., only the highest score of items 1-4, 6-9, and 15-16 are counted). Scores range from 0-3, with higher scores indicating more severe symptoms. Total scores range from 0-27, with scores \>= 21 considered very severe, 20-16 severe, 11-15 moderate, and 6-10 mild depression.
Time frame: Endpoint (Week 2)
Population: Intent-to-treat population analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low-frequency (1 Hz) rTMS | Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) | 12.66 score on a scale | Standard Deviation 6.63 |
| High-frequency (10 Hz) rTMS | Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) | 15.00 score on a scale | Standard Deviation 7.15 |
| Sham rTMS | Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-SR) | 9.42 score on a scale | Standard Deviation 4.68 |
p-value: 0.54Mixed Models Analysis