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

Treatment-resistant Depression Clinical Trial

— ChangePDD  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04996433
• Other study ID #: BR 4262/6-1
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2021
• Est. completion date: May 2026

Study information

• Verified date: October 2023
• Source: University of Greifswald
• Contact: Eva-Lotta Brakemeier, Prof. Dr.
• Phone: +49 3834 420
• Email: eva-lotta.brakemeier[@]uni-greifswald.de
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 mediators of change.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 396
• Est. completion date: May 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Persistent Depressive Disorder
• Treatment-resistant Depression

Intervention

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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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).
• 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)
• 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).
• 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).

Drug:
• 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.

Locations

Country	Name	City	State
Germany	Charité, University Medicine Berlin	Berlin
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universität zu Lübeck	Lübeck
Germany	Universitätsklinikum Marburg	Marburg
Germany	Klinikum der Universität München	München
Germany	Universitätsklinikum Tübingen	Tübingen

Sponsors (10)

Lead Sponsor	Collaborator
University of Greifswald	Charite University, Berlin, Germany, German Research Foundation, Hannover Medical School, Ludwig-Maximilians - University of Munich, Philipps University Marburg Medical Center, University Hospital Lübeck, University Hospital Tuebingen, University Medicine Greifswald, University of Kassel

Country where clinical trial is conducted

Germany, 

References & Publications (25)

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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. — View Citation

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. — View Citation

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, Normann C. Praxisbuch CBASP: Behandlung chronischer Depression; mit Online-Materialien (1. Aufl). 2012. 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. — View Citation

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Guhn 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. — View Citation

Harter 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. — View Citation

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Kohler 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. — View Citation

McCullough JP, Schramm E, Penberthy K. CBASP as a Distinctive Treatment for Persistent Depressive Disorder. 2014; Routledge. https://doi.org/10.4324/9781315743196

Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT, McCullough JP Jr, Weiss PM, Dunner DL, Rothbaum BO, Kornstein S, Keitner G, Keller MB. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14293-6. doi: 10.1073/pnas.2336126100. Epub 2003 Nov 13. Erratum In: Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16530. — View Citation

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Sabass L, Padberg F, Normann C, Engel V, Konrad C, Helmle K, Jobst A, Worlitz A, Brakemeier EL. Cognitive Behavioral Analysis System of Psychotherapy as group psychotherapy for chronically depressed inpatients: a naturalistic multicenter feasibility trial. Eur Arch Psychiatry Clin Neurosci. 2018 Dec;268(8):783-796. doi: 10.1007/s00406-017-0843-5. Epub 2017 Sep 27. — View Citation

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Spates CR, Pagoto SL, Kalata A. A qualitative and quantitative review of behavioral activation treatment of major depressive disorder. The Behavior Analyst Today. 2006; 7(4): 508-521. https://doi.org/10.1037/h0100089

Struck N, Krug A, Yuksel D, Stein F, Schmitt S, Meller T, Brosch K, Dannlowski U, Nenadic I, Kircher T, Brakemeier EL. Childhood maltreatment and adult mental disorders - the prevalence of different types of maltreatment and associations with age of onset and severity of symptoms. Psychiatry Res. 2020 Nov;293:113398. doi: 10.1016/j.psychres.2020.113398. Epub 2020 Aug 30. — View Citation

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Childhood Trauma Questionnaire (CTQ)	Childhood maltreatment by the definition of the World Health Organization (WHO) is assessed as a main moderator at baseline. The CTQ measures self-reported childhood trauma on five subscales. Responses are measured on a five point scale, and each subscale score has a range from 5 to 25 points. Higher scores indicate a higher severity in childhood trauma and therefore a worse outcome.	Baseline
Other	Brain-derived neurotrophic factor (BDNF)	Brain-derived neurotrophic factor (BDNF) methylation as a main moderator.	Baseline
Other	Inventory of Interpersonal Problems-revised (IIP-32-R)	The IIP-32-R is a self-reported questionnaire that assesses the severity of interpersonal problems on eight scales based on the two-dimensional interpersonal circumplex model as a main mediator. The items are rated on a five-point scale by the patients. A mean score is calculated, ranging from 0 to 4. A higher score indicates a higher severity of interpersonal problems and therefore a worse outcome.	Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
Other	Behavioral Activation Depression Scale (BADS)	This self-report is designed to measure weekly changes in avoidance and activation during treatment with Behavioral Activation for depression. The BADS consists of 25 questions on four subscales, each rated on a seven point scale ranging from 0 to 6. The subscales are activation, avoidance/rumination, work/school impairment, and social impairment. A higher total score represents a higher level of activation and therefore a better outcome, while a high score in the subscale social impairment indicates a higher level of impairment and therefore a worse outcome. Scores range from 0 to 150.	Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
Other	Step counts	Actimeter-measured step-counts as a main mediator.	Baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16 and 64
Primary	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.	16 weeks
Secondary	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.	baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 64
Secondary	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.	baseline, weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 40, 48, 56, 64
Secondary	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.	baseline, weeks 1, 5, 10, 16, 64
Secondary	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.	baseline, weeks 1, 5, 10, 16, 64
Secondary	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.	baseline, weeks 1, 5, 10, 16, 64
Secondary	Response	Response (50% decrease on HDRS-24 score)	baseline, weeks 1, 5, 10, 16, 64
Secondary	Remission	Remission (HDRS-24 score of 10 or less)	baseline, weeks 1, 5, 10, 16, 64
Secondary	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.	16, 64
Secondary	Cost interview	The cost interview assesses direct medical and non-medical costs and indirect costs due to mental disorders versus physical illnesses.	baseline, weeks 16 and 64