Post-Traumatic, Stress Disorders
Conditions
Keywords
PTSD
Brief summary
The purpose of this research of 400 participants is to determine whether a drug called risperidone can decrease symptoms of Post-Traumatic Stress Disorder (PTSD). It is a placebo-controlled study, meaning that half of the participants will be assigned to receive a pill that contains no drug. The treatment phase of the study will last for 6 months, during which time participants will continue to receive all their usual treatments in addition to the study treatment and will be asked to complete procedures and assessments (questionnaires, interviews, laboratory tests, physical exams, etc.) related to their PTSD symptoms at various points within the 6-month treatment phase. At the end of the 6-month study, participants will discontinue the study treatment.
Detailed description
Primary Hypothesis: Risperidone will reduce symptoms of PTSD, relative to placebo, in veterans with military service related chronic PTSD who have been partial or non-responders to antidepressant medications. Secondary Hypothesis: Risperidone is safe and well-tolerated in veterans with military service related chronic PTSD, and patients will comply with its prescription. As a result, patients will show improvement in the secondary consequences of PTSD for the veteran and for the VA. Intervention: Usual (PTSD) care plus Risperidone vs usual (PTSD) care plus placebo Study Abstract: Four hundred veterans with the diagnosis of military-related PTSD will be enrolled at 20 VAMC hospitals over a two-year period. An equipoise stratification design will be used to randomize patients in a double-blind manner to risperidone or placebo (\ 200 patients in each group) for six months of treatment. Usual care will be provided for all patients for treatment of PTSD and other psychiatric and medical disorders. Comparisons between the risperidone and placebo groups will be made at the end of six months to answer the primary question. The sample size is calculated to give 90% power at the two-sided alpha level of 0.05 for the overall test for the CAPS score change. STUDY UPDATE/NOTES: The study kicked-off in late July 2006 with recruitment expected to begin October 1, 2006. Oct2006 - Participating sites are seeking approval for the protocol amendment which resulted from the Kick-Off meeting. Patient recruitment at each site will begin as soon as they receive approval of the amendment.
Interventions
DRUGRisperidone
Initiate treatment with a low dose (1 mg/day HS) for week one, increasing by 1 mg/day weekly to a target dose of 3 mg/day. Escalation to a maximum of 4 mg/day will be allowed after a minimum of 4 weeks at the target dose (3 mg/day). Reduction to a lower dose will be allowed at any time, based on adverse effects. Treatment will continue for 6 months. Patients who discontinue treatment will be allowed to resume treatment at any time.
DRUGPlacebo
Placebo
Sponsors
Janssen, LP
US Department of Veterans Affairs
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 No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years or older * Military service related chronic PTSD * CAPS score \>50 * Participant in VA outpatient PTSD clinic * History of non-response to two or more antidepressants
Exclusion criteria
* Comorbid Axis I diagnosis requiring antipsychotic medication * Substance dependence diagnosis (excluding nicotine) * Hepatic or renal problems * Incompatible medical diagnosis or medication (i.e., coumadin, insulin) * Unstable living arrangements * Assault or suicide gesture within 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CAPS Score From Baseline to Week 24 | 24 Weeks | The primary outcome measure for this study was the total score on the 34-item Clinician-Administered PTSD Scale (CAPS). This study was the intent-to-treat analysis of the improvement in PTSD symptoms from baseline to week-24 follow-up as measured by the CAPS. Total score range for the CAPS is 0-136 with higher values representing a worse outcome. This study was powered initially to detect a 9-point difference between the treatment groups in the CAPS change score. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited initially from 20 VA Medical Centers over a 2-year period. To address low recruitment rates and other issues, 8 sites were discontinued and 6 sites were added during the course of the study.
Participants by arm
| Arm | Count |
|---|---|
| Risperidone Risperidone : atypical antipsychotic | 133 |
| Sugar Pill PTSD
Placebo : Placebo | 134 |
| Total | 267 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Incarcerated | 0 | 1 |
| Overall Study | Intolerant of burden of visits | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Missing Source Documents | 14 | 15 |
| Overall Study | Moved | 1 | 0 |
| Overall Study | Other issue | 1 | 0 |
| Overall Study | Other psychiatric problem | 1 | 0 |
| Overall Study | Unable to return for appointments | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Sugar Pill | Risperidone | 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 | 134 Participants | 133 Participants | 267 Participants |
| Age, Continuous | 54.5 years STANDARD_DEVIATION 10.6 | 54.3 years STANDARD_DEVIATION 10.8 | 54.4 years STANDARD_DEVIATION 10.7 |
| Region of Enrollment United States | 134 participants | 133 participants | 267 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 130 Participants | 128 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 133 | 0 / 134 |
| serious Total, serious adverse events | 16 / 133 | 10 / 134 |
Outcome results
Primary
Change in CAPS Score From Baseline to Week 24
The primary outcome measure for this study was the total score on the 34-item Clinician-Administered PTSD Scale (CAPS). This study was the intent-to-treat analysis of the improvement in PTSD symptoms from baseline to week-24 follow-up as measured by the CAPS. Total score range for the CAPS is 0-136 with higher values representing a worse outcome. This study was powered initially to detect a 9-point difference between the treatment groups in the CAPS change score.
Time frame: 24 Weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Risperidone | Change in CAPS Score From Baseline to Week 24 | -16.3 units on a scale |
| Sugar Pill | Change in CAPS Score From Baseline to Week 24 | -12.5 units on a scale |