Posttraumatic Stress Disorder
Conditions
Keywords
PTSD,, posttraumatic, stress, disorder,, randomization,, placebo,, controlled
Brief summary
The study is 12-week randomized placebo controlled trial compared to topiramate to treat patients with posttraumatic stress disorder, according to DSM-IV criteria. Patients will receive topiramate or placebo, the dose will start with 25 mg/day and every week 25mg will be increment according to patients tolerance to side effects. Patients will be evaluated by blind raters using Clinician-Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI) , Beck Anxiety Inventory (BAI), 36-Item Short Form Health Survey (SF-36), Social Adjustment Scale (SAS). the outcomes will be improvement on Posttraumatic Stress Disorder (PTSD), Depression, Anxiety, quality of life and social adjustment scale according to scales above.
Detailed description
Seventy-two (72) patients will be randomly allocated, in a stratified manner, according to sex and comorbidity with depression, into two (2) groups: topiramate and routine clinical follow-up, and a group that would receive placebo pills and routine clinical follow-up. The patients will be submitted to evaluations by trained independent researchers, who will apply a structured clinical interview for DSM-IV in order to evaluate the presence of psychiatric disorders (SCID I and SCID-II); the scale of evaluation of the Impact Event Scale-IES; the frequency and intensity of the symptoms of PTSD and of the variations associated with the trauma (PTSD Scale administered by clinical personnel: Clinician-Administered PTSD Scale - CAPS); severity of depression: Beck Depression Inventory (BDI) and that of anxiety: Beck Anxiety Inventory (BAI); a scale for the evaluation of social adaptation: Social Adjustment Scale (SAS); a scale for the evaluation of Quality of Life: 36-Item Short Form Health Survey (SF-36) ; a scale for the evaluation of global functioning axis V of DSM-IV (AGF). The patients will receive active treatment for twelve (12) weeks. After this period, the patients who have been using topiramate and who have had an improvement in their clinical condition will continue to receive further treatment for another twelve (12) weeks. Patients will have their medication suspended after twenty four (24) weeks and will be followed-up for a further twenty four (24) weeks. Patients from the placebo group who showed improvement will continue to receive clinical follow-up for a further thirty six (36) weeks. Patients from the placebo group who showed a worsening in their clinical status, evaluated through the CGI, will be excluded from the study and sent for traditional treatment at the PROVE (Violence and Stress Program) clinic. Patients who terminated the active phase of the study who did not obtain a clinical improvement will be sent for traditional treatment at the PROVE clinic. The principal outcomes to be examined will be: Response (a decrease of 50% in the CAPS score starting from the baseline) and remission (lack of diagnostic criteria for PTSD in the CAPS). After the end of the treatment, the collected data will be tabulated and compared using parametric and non-parametric tests. In this study the validation of the CAPS scale for Portuguese will be carried out.
Interventions
DRUGTopiramate
patients will receive the active drug. The starting dose was 25 mg/day, with weekly increments of 25 mg/day, according to clinical status. The maximum dose considered was 200 mg/day
initial dose 25 mg day, increments of 25 mg each 2 weeks. Up to 100 mg/day Those with no intolerance and no response dose could be up to 200 mg day
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Outpatient, male and female 18 to 60 yrs old * PTSD diagnostic according to DSM-IV criteria * Patients who agree to receive diagnostic after SCID I application by a trained psychiatrist * Sexually active female patients who agree to use contraceptive * Patients who agree to sign the IRB approved informed consent
Exclusion criteria
* Patients who have schizophrenic disorder, delusional, psychotic depression, schizo-affective, bipolar and dependence to psychoactive substance disorders * Patients who have clinical disorders not compensated, which require clinical treatment as priority * Pregnancy * Previous renal calculosis history * Being under antidepressant, or other psychotropic medications * BMI under 20.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician Administered Posttraumatic Stress Disorder Scale | 12 week | The Clinician-Administered PTSD Scale (CAPS) \[33\] : is a structured interview developed to diagnose PTSD and rate its severity. It is comprised of 30-items to assess PTSD-related symptom frequency and severity. Total scores (sum of 3 clusters items) range from 0 to 136, with scores classified as follows: subclinical, from 0 to 19; mild, from 20 to 39; moderate, from 40 to 59; severe, from 60 to 79; extreme, 80 and above. CAPS has 3 subscales characterized by the sum of all symptoms for each cluster: CAPS 1 (Revivesce/intrusive recolllections, 5 symptoms, score range: 0-28); CAPS 2 (avoidance, 7 symptoms, score range: 0-36); and CAPS 3 (hyperarousal, 5 symptoms, score range: 0-28). CAPS scoring: each symptom scores range from 0 to 4, plus 0-2 scores for frequency, and 0-2 severity. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate patients receiving the active drug: topiramate | 17 |
| Control Group patients received pills content placebo, that were identical to the pills content active drug | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 6 |
Baseline characteristics
| Characteristic | Topiramate | Control Group | 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 | 17 Participants | 18 Participants | 35 Participants |
| Age, Continuous | 43.7 years STANDARD_DEVIATION 13.44 | 36.5 years STANDARD_DEVIATION 7.97 | 37.54 years STANDARD_DEVIATION 12.08 |
| Clinician Administered Posttraumatic Scale (CAPS) Avoidance/numbing symptoms (CAPS-C) | 31.58 scores on a scale STANDARD_DEVIATION 7.13 | 24.78 scores on a scale STANDARD_DEVIATION 11.3 | 28.6 scores on a scale STANDARD_DEVIATION 4.79 |
| Clinician Administered Posttraumatic Scale (CAPS) Hyperarousal symptoms (CAPS-D) | 24.11 scores on a scale STANDARD_DEVIATION 5.69 | 20.14 scores on a scale STANDARD_DEVIATION 8.29 | 22.03 scores on a scale STANDARD_DEVIATION 3.8 |
| Clinician Administered Posttraumatic Scale (CAPS) Reexperiencing symptoms (CAPS-B) | 23.05 scores on a scale STANDARD_DEVIATION 5.88 | 21.21 scores on a scale STANDARD_DEVIATION 7.15 | 22.84 scores on a scale STANDARD_DEVIATION 3.85 |
| Clinician Administered Posttraumatic Scale (CAPS) Total CAPS | 79.64 scores on a scale STANDARD_DEVIATION 12.03 | 64.33 scores on a scale STANDARD_DEVIATION 22 | 72.43 scores on a scale STANDARD_DEVIATION 16.73 |
| Region of Enrollment Brazil | 17 participants | 18 participants | 35 participants |
| Sex: Female, Male Female | 12 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 5 Participants | 5 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 | 12 / 17 | 11 / 18 |
| serious Total, serious adverse events | 0 / 17 | 0 / 18 |
Outcome results
Primary
Clinician Administered Posttraumatic Stress Disorder Scale
The Clinician-Administered PTSD Scale (CAPS) \[33\] : is a structured interview developed to diagnose PTSD and rate its severity. It is comprised of 30-items to assess PTSD-related symptom frequency and severity. Total scores (sum of 3 clusters items) range from 0 to 136, with scores classified as follows: subclinical, from 0 to 19; mild, from 20 to 39; moderate, from 40 to 59; severe, from 60 to 79; extreme, 80 and above. CAPS has 3 subscales characterized by the sum of all symptoms for each cluster: CAPS 1 (Revivesce/intrusive recolllections, 5 symptoms, score range: 0-28); CAPS 2 (avoidance, 7 symptoms, score range: 0-36); and CAPS 3 (hyperarousal, 5 symptoms, score range: 0-28). CAPS scoring: each symptom scores range from 0 to 4, plus 0-2 scores for frequency, and 0-2 severity.
Time frame: 12 week
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Clinician Administered Posttraumatic Stress Disorder Scale | 30.41 Total CAPS score | Standard Deviation 30.9 |
| Control Group | Clinician Administered Posttraumatic Stress Disorder Scale | 35.78 Total CAPS score | Standard Deviation 33.76 |
p-value: 0.0076t-test, 2 sided