Clinical trial NCT04996433: A Comparison of Two Psychotherapy Programs in Persistently Depressed Treatment-Resistant Inpatients
Official title: Cognitive Behavioral Analysis System of Psychotherapy (CBASP) vs. Behavioral Activation (BA) in Persistently Depressed Treatment-resistant Inpatients: Efficacy, Moderators, and Mediators of Change
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Persistent Depressive Disorder
Treatment-resistant Depression
Keywords: Psychotherapy
Depression
Inpatient Treatment
Childhood Maltreatment
Epigenetic
Moderator
Mediator
Efficacy
Lead sponsor: University of Greifswald
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: University of Kassel
name: University Medicine Greifswald
name: Charite University, Berlin, Germany
name: Hannover Medical School
name: University Hospital Lübeck
name: Philipps University Marburg
name: Ludwig-Maximilians - University of Munich
name: University Hospital Tuebingen
First posted: 2021-08-09
Enrollment: 396
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, multicenter, evaluator-blinded, parallel-group, randomized controlled intervention trial with an active control condition
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) conducted over 16 weeks (acute and continuation treatment) with Behavioral Activation (BA; same dose and duration) in persistently depressed treatment-resistant inpatients regarding efficacy, moderators and mediators of change.

Detailed description: About half of all psychiatric inpatients with depression suffer from persistent depressive disorder (PDD). Given their high degree of treatment-resistance (TR), comorbidity, suicidality, and hospitalization rates, this patient group appears to be particularly difficult to treat and, from a health economic perspective, constitutes a major challenge. The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) is the only psychotherapy specifically tailored for PDD developed. Originally developed as an outpatient treatment by James P. McCullough, CBASP has been modified for the severely ill PDD patients with TR as a multimodal inpatient concept. Pilot studies indicate very good feasibility and promising outcome. Therefore, a randomized controlled trial is now mandatory for testing the superiority of the inpatient CBASP program vs. the evidence-based Cognitive Behavioral Therapy (CBT), the 'gold standard' in depression treatment. Behavioral Activation (BA) was chosen as the control intervention because BA, as a specific variant of CBT, is at least as effective as standard CBT in severely depressed patients while being easier to train and implement in inpatient settings. Both therapies will be applied as a treatment-phase program (5-week inpatient and dayclinic acute treatment followed by 6-week outpatient continuation group-treatment) in combination with standardized and guideline-based pharmacotherapy. The proposed prospective, multi-center, randomized study with 396 PDD patients with TR will therefore address the primary research question: Is the CBASP program more effective than the BA program in this patient group? The primary hypothesis is that after 16 weeks of treatment, CBASP will show a significant superiority over BA in reducing depressive symptoms. In addition, the important psychotherapy research question: what works for whom and why? will be addressed.

Moderator analyses will examine whether childhood maltreatment and methylation of exon IV of the BDNF gene have an impact on the differential efficacy of the treatments. Regarding mediator analyses, it will be examined whether symptom improvements can be explained by an amelioration of interpersonal problems in CBASP and an increase of activity levels in BA. A follow-up survey 48 weeks after the end of the interventions will provide valuable results regarding the long-term outcome of the treatments. Finally, the health economic potential of the interventions will be investigated through cost-benefit analyses in order to provide important information on the cost-effectiveness of implementation in routine care for health policy. Thus, the results of this study will have the potential to relieve the burden of this very serious and cost-intensive disorder while improving human health. In addition, moderator and mediator analyses may guide personalized treatment and enable therapists to more specifically address psychotherapeutic needs of individual PDD patients in the future.

Eligibility criteria: Inclusion Criteria:

* Primary DSM-5 diagnosis of PDD (300.4, 296.2x, 296.3x)
* Total Hamilton Depression Rating Scale (HDRS-24) Score ≥ 20
* Treatment-resistance (TR) (defined as a level of 3 or higher on the Antidepressant Treatment History Form: Short Form (ATHF-SF) or medication intolerance or one psychotherapy at least 25 sessions by a certified therapist in the current episode)
* Sufficient knowledge of the German language
* Written informed consent

Exclusion Criteria:

* Bipolar I or II disorder
* Active substance use disorders (abstinence shorter than 6 months)
* Schizophrenia spectrum and other psychotic disorders
* Antisocial personality disorder
* Acute suicidality
* Previous CBASP or BA treatment within the last year
* Inability to tolerate CBASP or BA (e.g., organic brain disorders, severe cognitive deficits)
* Inability to participate in dayclinic or outpatient continuation treatment

Primary outcomes:
measure: Hamilton Depression Rating Scale (HDRS-24), 24-item version
timeFrame: 16 weeks
Secondary outcomes:
measure: Hamilton Depression Rating Scale (HDRS-24), 24-item version
timeFrame: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 64
measure: Inventory of Depressive Symptomatology, Self-Report (IDS-SR)
timeFrame: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 40, 48, 56, 64
measure: Brief Symptom Inventory (BSI)
timeFrame: baseline, weeks 1, 5, 10, 16, 64
measure: Global Assessment of Functioning (GAF)
timeFrame: baseline, weeks 1, 5, 10, 16, 64
measure: World Health Organization Quality of Life (WHOQoL-BREF)
timeFrame: baseline, weeks 1, 5, 10, 16, 64
measure: Response
timeFrame: baseline, weeks 1, 5, 10, 16, 64
measure: Remission
timeFrame: baseline, weeks 1, 5, 10, 16, 64
measure: Relapse rates
timeFrame: 16, 64
measure: Cost interview
timeFrame: baseline, weeks 16 and 64
Other outcomes:
measure: Childhood Trauma Questionnaire (CTQ)
timeFrame: Baseline
measure: Brain-derived neurotrophic factor (BDNF)
timeFrame: Baseline
measure: Inventory of Interpersonal Problems-revised (IIP-32-R)
timeFrame: Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
measure: Behavioral Activation Depression Scale (BADS)
timeFrame: Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
measure: Step counts
timeFrame: Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
Locations:
city: Berlin
country: Germany
facility: Charité, University Medicine Berlin
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Lübeck
country: Germany
facility: Universität zu Lübeck
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg
city: München
country: Germany
facility: Klinikum der Universität München
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
Study officials:
affiliation: University Greifswald
name: Eva-Lotta Brakemeier, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
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