Persistent Depressive DisorderChangePDDNCT04996433
A Comparison of Two Psychotherapy Programs in Persistently Depressed Treatment-Resistant Inpatients
A study testing inpatient CBASP individual therapy, inpatient CBASP group therapy and inpatient CBASP nurse contact in people with Persistent Depressive Disorder and Treatment-resistant Depression, run by University of Greifswald at 8 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Persistent Depressive Disorder, Treatment-resistant Depression
- What is being tested?
- inpatient CBASP individual therapy, inpatient CBASP group therapy and inpatient CBASP nurse contact
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 396 participants
- Where
- 8 sitesGermany
- Study dates
- 1 Dec 2021to Apr 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Germany8 sites, 7 recruiting
- Recruiting
Charité, University Medicine Berlin
Berlin, State of Berlin, 10117
Stephan Köhler, Prof. Dr., 49-30-450 ext. 617408, stephan.koehler@charite.de
Henrik Walter, Prof. Dr.
- Recruiting
Universitätsklinikum Bonn
Bonn, 53127
Alexandra Philipsen, Prof. Dr., +49-228-287-15723, alexandra.philipsen@ukbonn.de
Silke Lux, Prof. Dr., +49-228-287-16368, silke.lux@ukbonn.de
- Terminated
Medizinische Hochschule Hannover
Hanover, 30625
- Recruiting
Universitätsklinikum Jena
Jena, 07743
Nils Opel, Prof. Dr., +49 - 3641-9-390101, nils.opel@med.uni-jena.de
Martin Walter, Prof. Dr., +49-3641-9390102, martin.walter@med.uni-jena.de
- Recruiting
Universität zu Lübeck
Lübeck, 23562
Philipp Klein, PD Dr., +49-451-500-98871, philipp.klein@uksh.de
Bartosz Zurowski, Dr. med., +49-451-500-98831, bartosz.zurowski@uksh.de
- Recruiting
Universitätsklinikum Marburg
Marburg, 35039
Tilo Kircher, Prof. Dr., +49-6421-58-65200, tilo.kircher@staff.uni-marburg.de
Ina Kluge, Dr., +49-6421-58-6219, ina.kluge@staff.uni-marburg.de
- Recruiting
Klinikum der Universität München
München, 80336
Frank Padberg, Prof. Dr., +49-89 4400-53358, frank.padberg@med.uni-muenchen.de
Matthias Reinhard, Dr., +49-89 4400-55512, matthias.reinhard@med.uni-muenchen.de
- Recruiting
Universitätsklinikum Tübingen
Tübingen, 72076
Andreas Fallgatter, Prof. Dr., +49-7071-29-84858, andreas.fallgatter@med.uni-tuebingen.de
Rainald Mössner, Prof. Dr., +49-7071-29-4141, rainald.moessner@med.uni-tuebingen.de
About this study
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
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.
Read the 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.
- Being tested
- inpatient CBASP individual therapy, inpatient CBASP group therapy, inpatient CBASP nurse contact, inpatient CBASP exercise therapy, outpatient CBASP group therapy
- Keywords
- Psychotherapy, Depression, Inpatient Treatment, Child Maltreatment, Epigenetic, Moderator, Mediator, Efficacy
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inpatient CBASP individual therapyBehavioural
Also called Cognitive Behavioral Analysis System of Psychotherapy - inpatient 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).
inpatient CBASP group therapyBehavioural
Also called Cognitive Behavioral Analysis System of Psychotherapy - inpatient 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).
inpatient CBASP nurse contactBehavioural
Also called Cognitive Behavioral Analysis System of Psychotherapy - inpatient 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).
inpatient CBASP exercise therapyBehavioural
Also called Cognitive Behavioral Analysis System of Psychotherapy - inpatient 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).
outpatient CBASP group therapyBehavioural
Also called Cognitive Behavioral Analysis System of Psychotherapy - outpatient 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).
inpatient BA individual therapyBehavioural
Also called Behavioral Activation - inpatient 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).
inpatient BA group therapyBehavioural
Also called Behavioral Activation - inpatient 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).
inpatient BA nurse contactBehavioural
Also called Behavioral Activation - inpatient 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)
inpatient BA exercise therapyBehavioural
Also called Behavioral Activation - inpatient 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).
outpatient BA group therapyBehavioural
Also called Behavioral Activation - outpatient 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).
algorithm-based study medicationDrug
Also called antidepressant 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.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Behavioral Analysis System of Psychotherapy (CBASP) | Experimental | 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). Receives: Behavioral: inpatient CBASP individual therapy; Behavioral: inpatient CBASP group therapy; Behavioral: inpatient CBASP nurse contact; Behavioral: inpatient CBASP exercise therapy; Behavioral: outpatient CBASP group therapy; Drug: algorithm-based study medication |
| Behavioral Activation (BA) | Active comparator | 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). Receives: Behavioral: inpatient BA individual therapy; Behavioral: inpatient BA group therapy; Behavioral: inpatient BA nurse contact; Behavioral: inpatient BA exercise therapy; Behavioral: outpatient BA group therapy; Drug: algorithm-based study medication |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale (HDRS-24), 24-item version
The change in HDRS-24 item score after 16 weeks will be the primary endpoint. The HRSD-24 is a semi-structured interview which is used to measure the severity of all symptom domains of depression as described by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) over a period of the last 7 days. It shows good psychometric properties. The HRSD-24 will be conducted by blind study raters at every time point. Raters evaluate symptom severity on a scale from 0 to 2 or 0 - 3 or 0 - 4 for each item, with higher number indicating higher symptom severity. The total score ranges from 0 to 75 with higher values indicating higher depression severity.
Measured: 16 weeks
Secondary outcomes (9)
Hamilton Depression Rating Scale (HDRS-24), 24-item version
The HDRS-24 is a semi-structured interview which is used to measure the severity of all symptom domains of depression as described by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) over a period of the last 7 days. It shows good psychometric properties. The HDRS-24 will be conducted by blind study raters at every time point. Raters evaluate symptom severity on a scale from 0 to 2 or 0 - 3 or 0 - 4 for each item, with higher number indicating higher symptom severity. The total score ranges from 0 to 75 with higher values indicating higher depression severity.
Measured: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 64
Inventory of Depressive Symptomatology, Self-Report (IDS-SR)
The IDS-SR is a self-reported measure of depressive symptoms and used to detect change in self-rated depression severity. It shows good psychometric properties. Each item is rated from 0 to 3 by the patient, and all values are added up to an overall score. Total score ranges from 0 to 78, with higher values indicating a higher depression severity.
Measured: baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 40, 48, 56, 64
Brief Symptom Inventory (BSI)
The BSI is a multi-dimensional self-reported measure with a total of nine scales assessing the subjective impairment by physical and psychological symptoms. Each item is rated on a scale from 0 to 5 by the patient and are added up and t-transformed to three global indices: Global Severity Index, Positive Symptom Distress Index, Positive Symptom Total. T-Scores range from 0 to 100, with higher values indicating a higher subjective impairment.
Measured: baseline, weeks 1, 5, 10, 16, 64
Global Assessment of Functioning (GAF)
The GAF is a diagnostic measure used to assess social, occupational and psychological functioning according to DSM-IV. The score ranges from 0 to 100 with a total of ten levels of functioning and is determined by a clinical rater. Higher scores indicate a higher level of functioning and therefore a better outcome.
Measured: baseline, weeks 1, 5, 10, 16, 64
World Health Organization Quality of Life (WHOQoL-BREF)
The WHOQoL-BREF is a self-reporting measure regarding the subjective quality of life. Four broad domains of quality of life are rated by the patient on a five point scale and a mean score for each domain is calculated. Scores range between 4 and 20, with a higher score indicating a higher quality of life and therefore a better outcome.
Measured: baseline, weeks 1, 5, 10, 16, 64
Response
Response (50% decrease on HDRS-24 score)
Measured: weeks 5, 10, 16, 64
Remission
Remission (HDRS-24 score of 10 or less)
Measured: weeks 5, 10, 16, 64
Relapse rates
Relapse rates (rehospitalization, increase of HDRS-24 of equal or greater than 10 or current HDRS-24 score of equal or greater than 18 points) are measured.
Measured: 16, 64
Cost interview
The cost interview assesses direct medical and non-medical costs and indirect costs due to mental disorders versus physical illnesses.
Measured: baseline, weeks 16 and 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start1 Dec 2021
- Primary completionAug 2026 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Persistent Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, multicenter, evaluator-blinded, parallel-group, randomized controlled intervention trial with an active control condition
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 396 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Greifswald
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation, University of Kassel, University Medicine Greifswald, Charite University, Berlin, Germany, Hannover Medical School, University Hospital Lübeck, Philipps University Marburg, Ludwig-Maximilians - University of Munich, University Hospital Tuebingen, University Hospital, Bonn, Jena University Hospital
- Responsible party
- Sponsor
- Investigators
- Eva-Lotta Brakemeier, Prof. Dr., Principal investigator, University Greifswald
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04996433
- Sponsor's protocol ID
- BR 4262/6-1
- Acronym
- ChangePDD
- Status last verified
- May 2026
- First submitted
- 27 Jun 2021
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with the Open Science specifications of the German Psychological Association (DGPS), anonymized data will be made available to the public via the Open Data portal of the Open Science Foundation (www.osf.io). The data will be stored when data collection is completed, but not before 01.01.2028. This step allows third parties to reproduce the analyses reported in scientific publications and to perform ad hoc analyses. The data is permanently stored on servers located in Germany. As soon as they are uploaded and published, these anonymized data cannot be deleted and are therefore also excluded from the deletion of the data in case of revocation of the study participation.
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 available.
PubMed 29306947Brakemeier 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.
PubMed 21389759Brakemeier 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.
PubMed 25547778Bschor 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.
PubMed 25467053Cuijpers 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.
PubMed 17184887DGPPN, BÄK, KBV, AWMF. S3-Leitlinie/Nationale Versorgungsleitlinie Unipolare Depression- Langfassung: Bd. Version 5 (2. Aufl.). 2015; Springer.
Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME, Gallop R, McGlinchey JB, Markley DK, Gollan JK, Atkins DC, Dunner DL, Jacobson NS. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol. 2006 Aug;74(4):658-70. doi: 10.1037/0022-006X.74.4.658.
PubMed 16881773Frieling H, Tadic A. Value of genetic and epigenetic testing as biomarkers of response to antidepressant treatment. Int Rev Psychiatry. 2013 Oct;25(5):572-8. doi: 10.3109/09540261.2013.816657.
PubMed 24151802Guhn A, Kohler S, Brakemeier EL, Sterzer P. Cognitive Behavioral Analysis System of Psychotherapy for inpatients with persistent depressive disorder: a naturalistic trial on a general acute psychiatric unit. Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):495-505. doi: 10.1007/s00406-019-01038-5. Epub 2019 Jul 12.
PubMed 31300878Harter M, Sitta P, Keller F, Metzger R, Wiegand W, Schell G, Stieglitz RD, Wolfersdorf M, Felsenstein M, Berger M. [Psychiatric-psychotherapeutic inpatient treatment for depression. Process and outcome quality based on a model project in Baden-Wurttemberg]. Nervenarzt. 2004 Nov;75(11):1083-91. doi: 10.1007/s00115-004-1705-8. German.
PubMed 15197451Holzel L, Wolff Av, Kriston L, Harter M. [Risk factors for non-response in inpatient depression treatment]. Psychiatr Prax. 2010 Jan;37(1):27-33. doi: 10.1055/s-0029-1223348. Epub 2009 Oct 12. German.
PubMed 19823968Kohler S, Sterzer P, Normann C, Berger M, Brakemeier EL. [Overcoming treatment resistance in chronic depression : The role of inpatient psychotherapy]. Nervenarzt. 2016 Jul;87(7):701-7. doi: 10.1007/s00115-015-0034-4. German.
PubMed 26610341
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04996433
- Acronym / sponsor ID
- ChangePDD / BR 4262/6-1
- Keywords
- Psychotherapy, Depression, Inpatient Treatment, Child Maltreatment, Epigenetic, Moderator, Mediator, Efficacy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 396 participants (estimated)
- Lead sponsor
- University of GreifswaldUniversity, hospital or other
- Collaborators
- German Research Foundation, University of Kassel, University Medicine Greifswald, Charite University, Berlin, Germany, Hannover Medical School, University Hospital Lübeck, Philipps University Marburg, Ludwig-Maximilians - University of Munich, University Hospital Tuebingen, University Hospital, Bonn, Jena University Hospital
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 9 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, multicenter, evaluator-blinded, parallel-group, randomized controlled intervention trial with an active control condition
| Arm | Type | Receives |
|---|---|---|
| Cognitive Behavioral Analysis System of Psychotherapy (CBASP) | Experimental | Behavioral: inpatient CBASP individual therapy, Behavioral: inpatient CBASP group therapy, Behavioral: inpatient CBASP nurse contact, Behavioral: inpatient CBASP exercise therapy, Behavioral: outpatient CBASP group therapy, Drug: algorithm-based study medicationCognitive 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). |
| Behavioral Activation (BA) | Active comparator | Behavioral: inpatient BA individual therapy, Behavioral: inpatient BA group therapy, Behavioral: inpatient BA nurse contact, Behavioral: inpatient BA exercise therapy, Behavioral: outpatient BA group therapy, Drug: algorithm-based study medicationBehavioral Activation (BA) as acute treatment (5 wk. inpatient and 5 wk. either inpatient or dayclinic) followed by continuation treatment (6 wk. outpatient group therapy). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inpatient CBASP individual therapyAlso: Cognitive Behavioral Analysis System of Psychotherapy - inpatient individual therapyDuring 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). | Behavioural | Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
| inpatient CBASP group therapyAlso: Cognitive Behavioral Analysis System of Psychotherapy - inpatient group therapyDuring 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). | Behavioural | Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
| inpatient CBASP nurse contactAlso: Cognitive Behavioral Analysis System of Psychotherapy - inpatient nurse contactDuring 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). | Behavioural | Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
| inpatient CBASP exercise therapyAlso: Cognitive Behavioral Analysis System of Psychotherapy - inpatient exercise therapyDuring 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). | Behavioural | Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
| outpatient CBASP group therapyAlso: Cognitive Behavioral Analysis System of Psychotherapy - outpatient group therapyDuring the 6-week outpatient treatment all patients in this arm will receive 1 CBASP group therapy session (duration: 100 min per session). | Behavioural | Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
| inpatient BA individual therapyAlso: Behavioral Activation - inpatient individual therapyDuring 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). | Behavioural | Behavioral Activation (BA) |
| inpatient BA group therapyAlso: Behavioral Activation - inpatient group therapyDuring 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). | Behavioural | Behavioral Activation (BA) |
| inpatient BA nurse contactAlso: Behavioral Activation - inpatient nurse contactDuring 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) | Behavioural | Behavioral Activation (BA) |
| inpatient BA exercise therapyAlso: Behavioral Activation - inpatient exercise therapyDuring 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). | Behavioural | Behavioral Activation (BA) |
| outpatient BA group therapyAlso: Behavioral Activation - outpatient group therapyDuring the 6-week outpatient treatment all patients in this arm will receive 1 BA group therapy session (duration: 100 min per session). | Behavioural | Behavioral Activation (BA) |
| algorithm-based study medicationAlso: antidepressant medicationAll 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. | Drug | Behavioral Activation (BA), Cognitive Behavioral Analysis System of Psychotherapy (CBASP) |
Primary outcome
Hamilton Depression Rating Scale (HDRS-24), 24-item version
Time frame: 16 weeks
The change in HDRS-24 item score after 16 weeks will be the primary endpoint. The HRSD-24 is a semi-structured interview which is used to measure the severity of all symptom domains of depression as described by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) over a period of the last 7 days. It shows good psychometric properties. The HRSD-24 will be conducted by blind study raters at every time point. Raters evaluate symptom severity on a scale from 0 to 2 or 0 - 3 or 0 - 4 for each item, with higher number indicating higher symptom severity. The total score ranges from 0 to 75 with higher values indicating higher depression severity.
9 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- BackgroundBernstein DP, Fink LA. CTQ: Childhood Trauma Questionaire: A retrospective self-report.1998; TX: Psychological Corp.
- Background: PubMed 29306947Brakemeier 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 available.
- Background: PubMed 21389759Brakemeier 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.
- BackgroundBrakemeier EL, Normann C. Praxisbuch CBASP: Behandlung chronischer Depression; mit Online-Materialien (1. Aufl). 2012. Weinheim: Beltz.
- BackgroundBrakemeier 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.
- Background: PubMed 25547778Brakemeier 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.
- Background: PubMed 25467053Bschor 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.
- Background: PubMed 17184887Cuijpers 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.
- BackgroundDGPPN, BÄK, KBV, AWMF. S3-Leitlinie/Nationale Versorgungsleitlinie Unipolare Depression- Langfassung: Bd. Version 5 (2. Aufl.). 2015; Springer.
- Background: PubMed 16881773Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME, Gallop R, McGlinchey JB, Markley DK, Gollan JK, Atkins DC, Dunner DL, Jacobson NS. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol. 2006 Aug;74(4):658-70. doi: 10.1037/0022-006X.74.4.658.
- Background: PubMed 24151802Frieling H, Tadic A. Value of genetic and epigenetic testing as biomarkers of response to antidepressant treatment. Int Rev Psychiatry. 2013 Oct;25(5):572-8. doi: 10.3109/09540261.2013.816657.
- Background: PubMed 31300878Guhn A, Kohler S, Brakemeier EL, Sterzer P. Cognitive Behavioral Analysis System of Psychotherapy for inpatients with persistent depressive disorder: a naturalistic trial on a general acute psychiatric unit. Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):495-505. doi: 10.1007/s00406-019-01038-5. Epub 2019 Jul 12.
- Individual participant dataSharing planned: Yes. In accordance with the Open Science specifications of the German Psychological Association (DGPS), anonymized data will be made available to the public via the Open Data portal of the Open Science Foundation (www.osf.io). The data will be stored when data collection is completed, but not before 01.01.2028. This step allows third parties to reproduce the analyses reported in scientific publications and to perform ad hoc analyses. The data is permanently stored on servers located in Germany. As soon as they are uploaded and published, these anonymized data cannot be deleted and are therefore also excluded from the deletion of the data in case of revocation of the study participation.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Eva-Lotta Brakemeier, Prof. Dr. principal investigator
University Greifswald
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing inpatient CBASP individual therapy, inpatient CBASP group therapy and inpatient CBASP nurse contact in people with Persistent Depressive Disorder and Treatment-resistant Depression, run by University of Greifswald at 8 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Eva-Lotta Brakemeier, Prof. Dr. (+49 3834 420 ext. 3718, eva-lotta.brakemeier@uni-greifswald.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Rating Scale (HDRS-24), 24-item version (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04996433, which also lists 26 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.