A Comparison of Two Psychotherapy Programs in Persistently Depressed Treatment-Resistant Inpatients

NCT ID: NCT04996433

Last Updated: 2023-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

396 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2026-05-31

Brief Summary

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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

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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.

Conditions

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Persistent Depressive Disorder Treatment-resistant Depression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, multicenter, evaluator-blinded, parallel-group, randomized controlled intervention trial with an active control condition
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Due to the nature of interventions, blinding of patients/therapists concerning the treatment program is impossible, but all assessments as well as data analysis will be blinded to treatment allocation. Notably, patients are blinded to the study hypothesis by the Informed Consent process, as patients are told in the patient information and educational discussions about the study that they will in any case receive one of two different scientifically based psychotherapy programs, although it is unclear which of the two programs is more effective. Similarly, the members of the treatment teams of each study ward are not informed about the study hypothesis; however, they are informed that it has not yet been scientifically clarified which therapy is more effective.

Study Groups

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Cognitive Behavioral Analysis System of Psychotherapy (CBASP)

Cognitive Behavioral Analysis System of Psychotherapy (CBASP) as acute treatment (5 wk. inpatient and 5 wk. either inpatient or dayclinic) followed by continuation treatment (6 wk. outpatient group therapy).

Group Type EXPERIMENTAL

inpatient CBASP individual therapy

Intervention Type BEHAVIORAL

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).

inpatient CBASP group therapy

Intervention Type BEHAVIORAL

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).

inpatient CBASP nurse contact

Intervention Type BEHAVIORAL

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: 30 min per session).

inpatient CBASP exercise therapy

Intervention Type BEHAVIORAL

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).

outpatient CBASP group therapy

Intervention Type BEHAVIORAL

During the 6-week outpatient treatment all patients in this arm will receive 1 CBASP group therapy session (duration: 100 min per session).

algorithm-based study medication

Intervention Type DRUG

All patients will receive an optimized, algorithm-based antidepressant medication following the current S3-Guidelines on Unipolar Depression. In case of nonresponse:

* 1st line dose escalation (if appropriate)
* 2nd line lithium augmentation
* 3rd line augmentation with 2nd generation antipsychotics or evidence-based combinations of antidepressants
* 4th line change of antidepressant.

Behavioral Activation (BA)

Behavioral Activation (BA) as acute treatment (5 wk. inpatient and 5 wk. either inpatient or dayclinic) followed by continuation treatment (6 wk. outpatient group therapy).

Group Type ACTIVE_COMPARATOR

inpatient BA individual therapy

Intervention Type BEHAVIORAL

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).

inpatient BA group therapy

Intervention Type BEHAVIORAL

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).

inpatient BA nurse contact

Intervention Type BEHAVIORAL

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: 30 min per session)

inpatient BA exercise therapy

Intervention Type BEHAVIORAL

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).

outpatient BA group therapy

Intervention Type BEHAVIORAL

During the 6-week outpatient treatment all patients in this arm will receive 1 BA group therapy session (duration: 100 min per session).

algorithm-based study medication

Intervention Type DRUG

All patients will receive an optimized, algorithm-based antidepressant medication following the current S3-Guidelines on Unipolar Depression. In case of nonresponse:

* 1st line dose escalation (if appropriate)
* 2nd line lithium augmentation
* 3rd line augmentation with 2nd generation antipsychotics or evidence-based combinations of antidepressants
* 4th line change of antidepressant.

Interventions

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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).

Intervention Type 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).

Intervention Type 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: 30 min per session).

Intervention Type 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).

Intervention Type 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).

Intervention Type 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).

Intervention Type 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).

Intervention Type 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: 30 min per session)

Intervention Type 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).

Intervention Type 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).

Intervention Type BEHAVIORAL

algorithm-based study medication

All patients will receive an optimized, algorithm-based antidepressant medication following the current S3-Guidelines on Unipolar Depression. In case of nonresponse:

* 1st line dose escalation (if appropriate)
* 2nd line lithium augmentation
* 3rd line augmentation with 2nd generation antipsychotics or evidence-based combinations of antidepressants
* 4th line change of antidepressant.

Intervention Type DRUG

Other Intervention Names

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Cognitive Behavioral Analysis System of Psychotherapy - inpatient individual therapy Cognitive Behavioral Analysis System of Psychotherapy - inpatient group therapy Cognitive Behavioral Analysis System of Psychotherapy - inpatient nurse contact Cognitive Behavioral Analysis System of Psychotherapy - inpatient exercise therapy Cognitive Behavioral Analysis System of Psychotherapy - outpatient group therapy Behavioral Activation - inpatient individual therapy Behavioral Activation - inpatient group therapy Behavioral Activation - inpatient nurse contact Behavioral Activation - inpatient exercise therapy Behavioral Activation - outpatient group therapy antidepressant medication

Eligibility Criteria

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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
Minimum Eligible Age

20 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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German Research Foundation

OTHER

Sponsor Role collaborator

University of Kassel

OTHER

Sponsor Role collaborator

University Medicine Greifswald

OTHER

Sponsor Role collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role collaborator

Hannover Medical School

OTHER

Sponsor Role collaborator

University Hospital Lübeck

OTHER

Sponsor Role collaborator

Philipps University Marburg

OTHER

Sponsor Role collaborator

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role collaborator

University of Greifswald

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva-Lotta Brakemeier, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Greifswald

Locations

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Charité, University Medicine Berlin

Berlin, , Germany

Site Status RECRUITING

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status NOT_YET_RECRUITING

Universität zu Lübeck

Lübeck, , Germany

Site Status RECRUITING

Universitätsklinikum Marburg

Marburg, , Germany

Site Status RECRUITING

Klinikum der Universität München

München, , Germany

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Eva-Lotta Brakemeier, Prof. Dr.

Role: CONTACT

+49 3834 420 ext. 3718

Johannes Zimmermann, Prof. Dr.

Role: CONTACT

+49 561 804 ext. 3833

Facility Contacts

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Stephan Köhler, Prof. Dr.

Role: primary

49-30-450 ext. 617405

Kai Kahl, Prof.Dr.

Role: primary

+49-511-532-2495

Ivo Heitland, Dr.

Role: backup

+49-511-532-7367

Philipp Klein, PD Dr.

Role: primary

+49-451-500-98871

Bartosz Zurowski, Dr.

Role: backup

+49-451-500-98831

Tilo Kircher, Prof. Dr.

Role: primary

+49-6421-58-65200

Ina Kluge, Dr.

Role: backup

+49-6421-58-6219

Frank Padberg (Co-PI of the trial), Prof. Dr.

Role: primary

+49-89 4400-53358

Matthias Reinhard, Dr.

Role: backup

+49-89 4400-55512

Andreas Fallgatter, Prof. Dr.

Role: primary

+49-7071-29-84858

Christian Frischholz, Dr.

Role: backup

+49-7071-29-86015

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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BR 4262/6-1

Identifier Type: -

Identifier Source: org_study_id

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