|- candidate number||7804|
|- NTR Number||NTR2235|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||1-mrt-2010|
|- Secondary IDs||80-82310-98-09034 ZonMw|
|- Public Title||Treatment study psychotrauma: Medication versus psychotherapy.|
Behandelstudie psychotrauma: Medicatie versus psychotherapie.
|- Scientific Title||The effectiveness of Paroxetine versus Trauma-Focused Cognitive Behavioural Therapy in the treatment of PTSD.|
|- hypothesis||The two most common interventions for Postraumatic Stress Disorder (PTSD) are pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and trauma focused psychological interventions such as trauma focused cognitive behavioural therapy (TF-CBT). National and international guidelines recommend trauma-focused psychological intervention for all PTSD patients although this recommendation is not based on clear-cut evidence from trials comparing pharmacological treatments with trauma focused psychological interventions. Finding out which intervention is most effective in symptom reduction and most cost-effective at the short- and long-term is highly relevant for clinical practice. |
|- Healt Condition(s) or Problem(s) studied||Post-Traumatic Stress Disorder (PTSD), Cognitive behavior therapy, Cost-effectiveness , SSRI|
|- Inclusion criteria||1. Patients with a diagnosis of chronic PTSD (> 3 months);|
2. CAPS score of 45 and higher;
3. Male and female, aged 18 years and above;
4. Written informed consent;
5. Eligible for exposure therapy.
|- Exclusion criteria||1. Suicidal risk;|
2. Presence of any of the following DSM IV diagnoses: Psychotic disorder incl. schizophrenia, a bipolar disorder, depression with psychotic features, or excessive substance related disorder over the past 6 months;
3. Female patients of childbearing potential must have a negative pregnancy test;
4. Primary diagnosis of severe depressive disorder;
5. Presence of primary or co-morbid personality disorder;
6. An organic disorder;
7. Intolerance to paroxetine or any other SSRI, taking psychotropic medications.
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-sep-2009|
|- planned closingdate||1-sep-2012|
|- Target number of participants||234|
|- Interventions||1. Trauma-focused cognitive behavioural therapy (TF-CBT), consisting of 12 weeksly sessions;|
2. Paroxetine (Seroxat) treatment lasts for 24 weeks. Treatment will be initiated at 20 mg daily for four weeks and can be increased by increments of 10mg/daily each four weeks up to a maximum of 60 mg/daily. Once response is obtained, the treatment will be maintained at that dose.
After 24 weeks of effective treatment with paroxetine the medication will be discontinued by gradual tapering the medication over at least 4 weeks (tapering off in 10 mg increments per week). Patients will be treated by certified psychiatrists.
|- Primary outcome||1. The change in Clinician Administered PTSD Scale (CAPS) at 1 week, 3 months, 6 months, 12 and 18 months after treatment;|
2. (Unit) costs associated with an improved PTSD outcome in terms of CAPS scores at 1 week, 3 months, 6 months and 12 and 18 months after treatment.
|- Secondary outcome||At 1 week, and 3, 6, 12 and 18 months post-intervention the following secondary outcomes will be assessed as well:|
1. Other psychopathology;
2. Quality of life;
3. Anxiety and depression and costs;
4. Neurocognitive, neuroimmune and genetic measures.
|- Timepoints||1. 1 week pretreatment and 3, 6, 12, and 18 months post-intervention;|
2. 2, 12 and 20 weeks weeks during treatment.
|- Trial web site||http://www.amcpsychiatrie-angst.nl|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Dr. M. Olff|
|- CONTACT for SCIENTIFIC QUERIES||Dr. M. Olff|
|- Sponsor/Initiator ||Academic Medical Center (AMC), Amsterdam, University of Amsterdam (UvA)|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Rationale:|
Post Traumatic Stress Disorder (PTSD) has a major health and economic burden on patients, their relatives and society as a whole. The two most common interventions for PTSD are pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and trauma focused psychological interventions such as trauma focused cognitive behavioural therapy (TF-CBT). Paroxetine is a well-tolerated and effective drug for treating anxiety disorders like PTSD in both male and female patients irrespective of comorbid disorders. TF-CBT consists of a broad array of techniques, including exposure to the traumatic memory and cognitive restructuring. National and international guidelines recommend trauma-focused psychological intervention for all PTSD patients although this recommendation is not based on clear-cut evidence from trials comparing pharmacological treatments with trauma focused interventions. Finding out which intervention is most effective in symptom reduction and most cost-effective at the short- and long-term is highly relevant for clinical practice.
Based on previous findings of the effects of both treatments on clinical symptomatology over time, our main objective is to study the effectiveness and cost-effectiveness of TF-CBT versus paroxetine on PTSD symptoms and CGI score at post-intervention. In addition, a cost-effectiveness analysis will be performed that evaluates costs associated with an improved PTSD outcome. Secondary objectives are to assess response rate, symptoms of anxiety and depression, quality of life, and costs in relation to symptom reduction in both treatments. Furthermore, effects of both treatments on neuroendocrine and neuroimmune parameters and neurocognitive functioning will be assessed and possible genetic polymorphisms will be explored.
We propose to conduct a randomised controlled trial (RCT) comparing TF-CBT with paroxetine and 18 months follow-up study.
Adult patients with chronic Posttraumatic Stress Disorder (PTSD). Participants will be recruited at the regular outpatient psychiatric clinic of the Academic Medical Centre (AMC) and from a current ongoing large cohort study, TRAUMA-TIPS on prediction and prevalence of PTSD in patients from trauma units. Participants will be assessed immediately preceding the intervention, 1 week after the treatment and at four follow-up moments (3, 6, 12 and 18 months after the treatment).
In this trial, we will assign participants suffering from chronic PTSD randomly to either 12-weekly sessions of TF-CBT (N = 117) or 24-weeks of flexible-dose open treatment (20 mg to a maximum of 60 mg) with paroxetine (N = 117).
Main study parameters/endpoints:
Main study parameter included is the change in PTSD symptom severity on the Clinician Administered PTSD Scale (CAPS) and improvement on the Clinical Global Impression scale (CGI-I) from pre-intervention baseline measurement to post-intervention measurement at follow-up assessments. The economic evaluation will be performed from a societal perspective, with the costs per unit improvement on the primary outcome (CAPS score) as the primary outcome measure.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The burden and risks associated with participation in this study is very limited, due to the naturalistic design of the study. The visits in the context of the interventions, pre-intervention blood samples and physical examinations and diagnostic questionnaires are all part of the usual care at the Zorglijn Angststoornissen, AMC Psychiatry. Additional and only in the context of the study are: laboratory assessments (blood samples) during the course of the treatments (at 2, 12 and 20 weeks), and at 1 week, 3, 6, 12, and 18 months post-intervention. Additional are also saliva sampling, a dexamethasone suppression-test and assessment of neurocognitive functioning and some extra questionnaire on costs and secondary study parameters (e.g., quality of life) at pre- and post-intervention assessments.
|- Main changes (audit trail)|
|- RECORD||1-mrt-2010 - 12-mrt-2010|