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

Not Applicable

• Conditions: Major Depressive Disorder; Childhood Trauma
• Interventions: Behavioral: Treatment as usual (TAU) for depression; Behavioral: Trauma-focused therapy (TFT)

• Registration Number: NCT05149352
• Lead Sponsor: Amsterdam UMC, location VUmc

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2021-11-02
• Study Start: 2021-11-10
• Study First Submitted QC: 2021-11-25
• Study First Posted: 2021-12-08
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-20
• Last Update Posted: 2022-04-27
• Primary Completion: 2024-03-01
• Study Completion: 2024-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 158

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment as usual (TAU)	Treatment as usual (TAU) for depression	Participants will receive an evidence-based psychotherapeutic intervention combined with/or pharmacotherapy (TAU)
Treatment as usual (TAU) + Trauma-focused therapy (TFT)	Treatment as usual (TAU) for depression	Participants will receive 6 to 10, 60-90 minute TFT sessions delivered over a period of 12 weeks, in addition to TAU.
Treatment as usual (TAU) + Trauma-focused therapy (TFT)	Trauma-focused therapy (TFT)	Participants will receive 6 to 10, 60-90 minute TFT sessions delivered over a period of 12 weeks, in addition to TAU.

Primary Outcome Measures

Name	Time	Method
Depressive symptom severity at post-treatment	Up to 12 weeks (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)

Secondary Outcome Measures

Name	Time	Method
Depressive symptom severity during treatment and at 9 months follow-up	Up to 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)
Remission in CT-related depression	Up to 9 monts (follow-up)	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).

Trial Locations

Locations (3)

GGZ inGeest; 🇳🇱 Amsterdam, Noord-Holland, Netherlands

HSK Groep; 🇳🇱 Woerden, Utrecht, Netherlands

Altrecht; 🇳🇱 Utrecht, Netherlands