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

Overview

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. 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 (10-week inpatient/ 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 child 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 the differential efficacy of the treatments can be explained by treatment-specific changes in interpersonal problems or activity levels. 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.

Interventions

• Behavioral inpatient CBASP individual therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 2 individual CBASP therapy sessions (duration: 50 min per session).
• Behavioral inpatient CBASP group therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 2 CBASP group therapy sessions (duration: 100 min per session).
• Behavioral inpatient CBASP nurse contact
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 1 CBASP nurse contact (duration: 25 min per session).
• Behavioral inpatient CBASP exercise therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 1 CBASP exercise therapy (duration: 75 min per session).
• Behavioral outpatient CBASP group therapy
  During the 6-week outpatient treatment all patients in this arm will receive 1 CBASP group therapy session (duration: 100 min per session).
• Behavioral inpatient BA individual therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 2 individual BA therapy sessions (duration: 50 min per session).
• Behavioral inpatient BA group therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 2 BA group therapy sessions (duration: 100 min per session).
• Behavioral inpatient BA nurse contact
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 1 BA nurse contact (duration: 25 min per session)
• Behavioral inpatient BA exercise therapy
  During the 5-week inpatient phase I and the 5-week inpatient phase II / dayclinic treatment all patients in this arm will receive 1 BA exercise therapy (duration: 75 min per session).
• Behavioral outpatient BA group therapy
  During the 6-week outpatient treatment all patients in this arm will receive 1 BA group therapy session (duration: 100 min per session).

Primary outcome measures

• Hamilton Depression Rating Scale (HDRS-24), 24-item version [Time frame: 16 weeks]

Secondary outcome measures (9)

• Hamilton Depression Rating Scale (HDRS-24), 24-item version [Time frame: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 64]
• Inventory of Depressive Symptomatology, Self-Report (IDS-SR) [Time frame: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 40, 48, 56, 64]
• Brief Symptom Inventory (BSI) [Time frame: baseline, weeks 1, 5, 10, 16, 64]
• Global Assessment of Functioning (GAF) [Time frame: baseline, weeks 1, 5, 10, 16, 64]
• World Health Organization Quality of Life (WHOQoL-BREF) [Time frame: baseline, weeks 1, 5, 10, 16, 64]
• Response [Time frame: weeks 5, 10, 16, 64]
• Remission [Time frame: weeks 5, 10, 16, 64]
• Relapse rates [Time frame: 16, 64]
• Cost interview [Time frame: baseline, weeks 16 and 64]

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 by the 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 (HRSD item 3 > 2 or agreement with C-SSRS item 4 and/or item 5)
• 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
• Participation in another (psycho)therapeutic study of an interventional nature

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Germany · 8 centers

• Charité, University Medicine Berlin — Berlin
• Universitätsklinikum Bonn — Bonn
• Medizinische Hochschule Hannover — Hanover
• Universitätsklinikum Jena — Jena
• Universität zu Lübeck — Lübeck
• Universitätsklinikum Marburg — Marburg
• Klinikum der Universität München — München
• Universitätsklinikum Tübingen — Tübingen

Publications

• Bernstein DP, Fink LA. CTQ: Childhood Trauma Questionaire: A retrospective self-report.1998; TX: Psychological Corp.
• Brakemeier EL, Dobias J, Hertel J, Bohus M, Limberger MF, Schramm E, Radtke M, Frank P, Padberg F, Sabass L, Jobst A, Jacob GA, Struck N, Zimmermann J, Normann C. Childhood Maltreatment in Women with Borderline Personality Disorder, Chronic Depression, and Episodic Depression, and in Healthy Controls. Psychother Psychosom. 2018;87(1):49-51. doi: 10.1159/000484481. Epub 2018 Jan 6. No abstract avai PMID 29306947
• Brakemeier EL, Engel V, Schramm E, Zobel I, Schmidt T, Hautzinger M, Berger M, Normann C. Feasibility and outcome of cognitive behavioral analysis system of psychotherapy (CBASP) for chronically depressed inpatients: a pilot study. Psychother Psychosom. 2011;80(3):191-4. doi: 10.1159/000320779. Epub 2011 Mar 10. No abstract available. PMID 21389759
• Brakemeier EL, Normann C. Praxisbuch CBASP: Behandlung chronischer Depression; mit Online-Materialien (1. Aufl). 2012. Weinheim: Beltz.
• Brakemeier EL, Guhn A, Normann C. Praxisbuch CBASP: Behandlung chronischer Depression und Modifikationen für weitere interpersonelle Störungen; mit E-Book inside und Arbeitsmaterial; (2., überarbeitete und erweiterte Auflage). 2021; Weinheim: Beltz.
• Brakemeier EL, Radtke M, Engel V, Zimmermann J, Tuschen-Caffier B, Hautzinger M, Schramm E, Berger M, Normann C. Overcoming treatment resistance in chronic depression: a pilot study on outcome and feasibility of the cognitive behavioral analysis system of psychotherapy as an inpatient treatment program. Psychother Psychosom. 2015;84(1):51-6. doi: 10.1159/000369586. Epub 2014 Dec 24. PMID 25547778
• Bschor T, Bauer M, Adli M. Chronic and treatment resistant depression: diagnosis and stepwise therapy. Dtsch Arztebl Int. 2014 Nov 7;111(45):766-75; quiz 775. doi: 10.3238/arztebl.2014.0766. PMID 25467053
• Cuijpers P, van Straten A, Warmerdam L. Behavioral activation treatments of depression: a meta-analysis. Clin Psychol Rev. 2007 Apr;27(3):318-26. doi: 10.1016/j.cpr.2006.11.001. Epub 2006 Dec 19. PMID 17184887

Identifiers

NCT: NCT04996433 · BR 4262/6-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗