RESET-psychotherapy: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma

Study Overview
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Brief Summary
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Depression is a debilitating psychiatric disorder with a recurrent and progressive course. Around 25% of depressive patients has experienced moderate to severe levels of childhood trauma (CT), resulting in earlier onset and more severe and recurrent depressions. There is currently no targeted treatment for CT-related depression. This is problematic as patients with CT-related depression respond poorly to standard depression treatments. The RESET-psychotherapy study proposes an innovative, targeted disease-modifying treatment strategy for CT-related depression. The main objective is to investigate the effectiveness of trauma-focused therapy (TFT), as an addition to regular depression treatment ('treatment as usual'; TAU), in reducing depression symptom severity in patients with CT-related depression. 158 adult patients will be randomized to receive a 12-week treatment with 1) TAU or 2) TFT in combination with TAU. The primary outcome measure is defined as depression symptom severity after 12 weeks treatment (post-treatment), measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR).

Detailed Description
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Depression is a debilitating psychiatric disorder with a recurrent and progressive course. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. Around 25% of depressive patients has experienced moderate to severe levels of childhood trauma (CT), ranging from physical and emotional neglect to emotional, physical and sexual abuse. There is increasing evidence that depression related to childhood trauma (CT) is critically different from non-CT related depression: it emerges earlier in life with more severe and recurrent symptoms and has worse treatment outcomes. Therefore, there is a large and unmet need for novel therapeutic strategies for CT-related depression. Currently, there is no targeted treatment available for CT-related depression. Given the major role of trauma in CT-related depression, it is plausible that trauma-focused psychotherapies may be effective in this depression subtype. The current study aims to investigate the effectiveness of trauma-focused therapy (TFT), as an addition to 'treatment as usual' (TAU), in reducing depression symptom severity in patients with CT-related depression. It is expected that trauma-focused therapy will be a safe and rational strategy to enhance resilience and improve depression outcomes for patients with CT-related depression. RESET-psychotherapy is a 12-week randomized controlled clinical trial (single-blind RCT), in which TFT in combination with TAU will be compared to TAU only at various specialized mental healthcare units of mental health care institutions. The study population will consist of 158 adult patients who have a diagnosis of moderate to severe depression (according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) and moderate to severe childhood trauma (CT). The primary outcome measure is defined as depression symptom severity after 12 weeks treatment (post-treatment), measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR). Data will be collected during multiple assessments: at baseline (T0), after 6 weeks (T1), after 12 weeks (T2; post-treatment), and after 6 months post-treatment (follow-up, T3). Information about depressive symptoms, childhood trauma and other health-related outcomes will be assessed using self-report questionnaires and semi-structured clinical interviews. In addition, to better understand how and for who TFT works, stress-related biomarkers (hair cortisol, inflammatory and epigenetic biomarkers in the blood) will be examined pre- and post-treatment. A sub-group of patients (N=60, 30 per intervention group) will be asked to undergo fMRI scans pre- and post-treatment to measure stress-related brain activity (fMRI sub-study, ±60 minutes per fMRI session).

Official Title
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REStoring Mood After Early Life Trauma: the Effectiveness of Trauma-focused Therapy in Patients With Depression and Childhood Trauma

Conditions
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Major Depressive Disorder, Childhood Trauma

Intervention / Treatment
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* Behavioral: Treatment as usual (TAU) for depression
* Behavioral: Trauma-focused therapy (TFT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe depression, defined by a score ≥ 26 on the Inventory of Depressive Symptomatology - Self Rated (IDS-SR) DSM-5 diagnosis of MDD confirmed with the Dutch translation of the MINI-S for DSM-5 Moderate to severe childhood trauma (CT) before the age of 18, defined by a score above validated cut-off on one or more of the following domains of the 28-item Childhood Trauma Questionnaire Short Form (CTQ-SF): physical neglect: score ≥ 10 emotional neglect: score ≥ 15 sexual abuse: score ≥ 8 physical abuse: score ≥10 emotional abuse: score ≥ 13 Sufficient mastery of Dutch language Exclusion Criteria: Previous TFT on CT Other lifetime severe psychiatric comorbidity (bipolar disorder, psychotic disorder) Current alcohol/drug dependence Primary diagnosis of post-traumatic stress disorder (PTSD) or Acute Stress Disorder (ASD) Lifetime diagnosis of borderline personality disorder (BPD)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to one of two treatment conditions. In one condition (control group) participants will receive a regular depression treatment that they would usually receive for their depression ('treatment as usual', TAU). In the other condition (intervention group) participants will receive trauma-focused therapy (TFT), additional and parallel to their depression treatment (TAU). In both treatment groups (TAU and TAU+TFT), treatment will be provided during a period of 12 weeks.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment as usual (TAU)<br>Participants will receive an evidence-based psychotherapeutic intervention combined with/or pharmacotherapy (TAU) | Behavioral: Treatment as usual (TAU) for depression<br>* TAU for depression will be largely determined by the Dutch multidisciplinary practice guideline on depression (Spijker et al., 2013). This means that patients with CT-related depression will receive good clinical care, e.g. evidence-based psychotherapeutic interventions, such as cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) combined with/or pharmacotherapy. Therapists who give TAU are not allowed to provide a trauma-focused intervention aimed at CT during the 12-week intervention period.<br>|
| Experimental: Treatment as usual (TAU) + Trauma-focused therapy (TFT)<br>Participants will receive 6 to 10, 60-90 minute TFT sessions delivered over a period of 12 weeks, in addition to TAU. | Behavioral: Treatment as usual (TAU) for depression<br>* TAU for depression will be largely determined by the Dutch multidisciplinary practice guideline on depression (Spijker et al., 2013). This means that patients with CT-related depression will receive good clinical care, e.g. evidence-based psychotherapeutic interventions, such as cognitive behavioral therapy (CBT) or interpersonal therapy (IPT) combined with/or pharmacotherapy. Therapists who give TAU are not allowed to provide a trauma-focused intervention aimed at CT during the 12-week intervention period.<br>Behavioral: Trauma-focused therapy (TFT)<br>* The content of TFT, delivered by another therapist than the therapist that will provide TAU, depends on the type of CT the patient reports. If the patient predominantly reports experiences of abuse, there are often clear memories of this abuse ('target images') present and Eye Movement Desensitization and Reprocessing (EMDR) is recommended as the treatment strategy. If the patient predominantly reports experiences of neglect, memories are often less identifiable, although these experiences can have a big impact on the development of maladaptive schemas. In this case, imagery rescripting (ImRs) is recommended as treatment strategy. If the patient reports both experiences of abuse and neglect, the therapist will discuss with the patient which type of CT has the greatest impact on the current depressive symptoms and starts with the indicated therapy. If indicated, the therapist can switch between EMDR and ImRs after a minimum of 4 sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptom severity at post-treatment | Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms) | Up to 12 weeks (post-treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptom severity during treatment and at 9 months follow-up | Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms) | Up to 9 months (follow-up) | 
| Remission in CT-related depression | The presence or absence of DSM-5 Major Depressive Disorder (MDD), identified using the Major Depressive Disorder (MDD) section of the Dutch translation of the Mini International Neuropsychiatric Interview-Simplified (MINI-S). | Up to 9 monts (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Childhood trauma, Trauma-focused, Psychotherapy, Treatment, EMDR, Imagery rescripting