Trauma-Focused Therapy in Major Depressive Disorder and Childhood Trauma

Personalized and targeted treatments for major depressive disorder (MDD) may be possible by using adjunctive trauma-focused therapy to alleviate depressive symptoms among those with MDD and with childhood trauma.

Researchers in an ongoing study hope to show that if adjunctive trauma-focused therapy alleviates depressive symptoms among patients with major depressive disorder (MDD) and childhood trauma efficaciously, it may lead to more personalized and targeted MDD treatment, according to a prestudy report published in BMC Psychiatry.

Researchers seek to evaluate whether trauma-focused therapy adjunctive to treatment as usual (TAU) leads to a greater reduction of depressive symptoms posttreatment vs TAU exclusively in patients with MDD with childhood trauma. The primary endpoint is self-reported depression symptom severity at posttreatment.

Researchers are conducting the ongoing RESET-psychotherapy study ( Identifier: NCT05149352), a 12-week single-blind, randomized controlled trial (RCT) to test the efficacy of trauma-focused therapy. Participants are recruited in the Netherlands from 3 mental health organization sites. This will be a superiority RCT with dual treatment arms (TAU; TAU plus trauma-focused therapy). They plan to include 158 adults with MDD and childhood trauma who will be randomly allocated (1:1) to 1 of the treatment arms. Researchers will invite a subgroup (n=30 in each arm) to participate in a functional magnetic resonance imaging (fMRI) sub-study to assess pre/posttreatment brain activity.

Significant inclusion criteria include being at least 18 years of age, a primary diagnosis of MDD (stand-alone depression diagnosis or superimposed on a persistent depressive disorder) confirmed with the Mini International Neuropsychiatric Interview — Simplified (MINI-S) for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5, a score of at least 26 (moderate to severe MDD) on the Inventory of Depressive Symptomatology —  Self Report (IDS-SR), moderate to severe childhood trauma validated by appropriate scores on the short form of the Childhood Trauma Questionnaire (CTQ-SF), and adequate mastery of Dutch.

If adjunctive TFT would be more efficacious than TAU only, this would be a novel hypothesis-driven treatment strategy for an important MDD subtype and pave the way for a more personalized and targeted MDD treatment.

Exclusion criteria identified through telephone screening included a primary diagnosis of posttraumatic stress disorder or acute stress disorder, lifetime diagnosis of borderline personality disorder, current substance use dependence, comorbid diagnosis of severe mental disorder, or previous trauma-focused therapy aimed at childhood trauma. The fMRI sub-study additionally excludes major internal or neurologic disorders, pregnancy, claustrophobia, and known contraindications for MRI.

Participants will be assessed before being randomly assigned (T0), during treatment (T1), posttreatment (T2), and at 6-month follow-up (T3). Participants will receive a €25 gift voucher for each completed assessment. trauma-focused therapy treatment includes 6 to 10, 60 to 90-minute individual trauma-focused therapy sessions of eye movement desensitization and reprocessing and/or imagery rescripting. Therapists providing trauma-focused therapy will not provide TAU for the same patient. Participants in the trauma-focused therapy treatment plus TAU will be compared with participants in TAU only. The nature of trauma-focused therapy demands patients and therapists be made aware of allocated treatment. Outcome assessors will be blinded to the allocation.

The primary endpoint will be assessed with the 30-item IDS-SR which measures the severity of depressive symptomology during the previous 7 days. Remission and depression symptom severity at follow-up and during treatment represent secondary outcomes. A shortened version of the clinician-administered Columbia-Suicide Severity Rating Scale will be offered in the event of participants reporting suicidal ideation, intentions, or plans.

At T0 and T2 hair samples close to scalp will be collected and assessed as a stable retrospective marker of long-term systemic cortisol levels. Blood samples will be taken at T0 and T2 for analysis on epigenetic and inflammatory markers (C-reactive protein, tumor necrosis factor-alpha, interleukin-6) underlying the effects of trauma-focused therapy.

Study limitations include participants in the study group receiving more treatment sessions than those in the TAU group, telephone screening being unreliable for determining exclusion criteria, and childhood trauma only being assessed by a retrospective self-report measure.

The study authors note, “If adjunctive TFT would be more efficacious than TAU only, this would be a novel hypothesis-driven treatment strategy for an important MDD subtype and pave the way for a more personalized and targeted MDD treatment.”

This article originally appeared on Psychiatry Advisor


Gathier AW, Verhoeven JE, van Oppen PC, et al. Design and rationale of the REStoring mood after early life trauma with psychotherapy (RESET-psychotherapy) study: a multicenter randomized controlled trial on the efficacy of adjunctive trauma-focused therapy (TFT) versus treatment as usual (TAU) for adult patients with major depressive disorder (MDD) and childhood trauma. BMC Psychiatry. Published online January 17, 2023. doi:10.1186/s12888-023-04518-0