{
  "abstract": "Introduction Up to 30% of individuals with depression develop persistent depressive disorder (PDD), an often disabling and difficult to treat condition. The Cognitive Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy developed specifically for treating individuals with PDD. While several randomised controlled trials (RCTs) have demonstrated its efficacy in outpatient settings, evidence for its use in inpatient settings remains limited. Pilot studies of CBASP inpatient programmes in Germany have shown promising feasibility and effectiveness; however, no RCTs to date have systematically evaluated their outcomes. This study represents the first RCT to compare the short- and long-term efficacy and safety of CBASP with Behavioural Activation (BA), a first-line psychotherapy for depression, within an intensive multimodal inpatient setting.Methods and analysis In this prospective, multicentre, rater-blinded RCT with an active control group, we aim to recruit 396 adults (aged 18–70 years) with treatment-resistant PDD at eight German university hospitals. Participants will be randomly assigned to receive either (1) CBASP or (2) BA within an intensive treatment programme consisting of 10 weeks acute treatment in an inpatient and/or day clinic setting, followed by 6 weeks of outpatient continuation treatment. Primary and secondary outcome assessments will be conducted at multiple time points: baseline (T0), treatment onset (T1), after 5 and 10 weeks of acute treatment (T2, T3), at the end of continuation treatment (T4, week 16) and every 2 months up to week 64 (T5, naturalistic follow-up).The primary outcome measure will be the change in depression severity, as assessed by the Hamilton Depression Rating Scale (24-item version), after 16 weeks of treatment (from T0 to T4). Secondary outcomes will include response, remission, deterioration and relapse rates, self-reported depression and anxiety symptoms and additional psychological variables. A cost-benefit analysis will evaluate the health-economic benefits of both interventions. Additionally, this RCT will explore personalised treatment selection and mechanisms of change, including potential moderators and mediators of treatment effects. The findings from this trial are expected to provide clinicians with evidence-based guidance on choosing CBASP versus BA for inpatients with treatment-resistant PDD.Ethics and dissemination This study has received ethical approval from the ethics committees of all participating university hospitals. All participants will provide written informed consent before enrolment. Study findings will be published in peer-reviewed journals and presented at national and international conferences. We have involved people with lived experience from the earliest pilots onward, using their feedback to refine our study design. Ongoing consultation at conferences and public events has further ensured that our research remains grounded in patient perspectives.Trial registration number NCT04996433.",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany"
      ],
      "name": "Eva-Lotta Brakemeier"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany"
      ],
      "name": "Jan Philipp Klein"
    },
    {
      "affiliations": [
        "Department of Psychology, University of Kassel, Kassel, Germany"
      ],
      "name": "Johannes Zimmermann"
    },
    {
      "affiliations": [
        "Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany"
      ],
      "name": "Maike Hollandt"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany",
        "Partner Site Munich-Augsburg, DZPG (German Center for Mental Health), Munich, Germany"
      ],
      "name": "Matthias A Reinhard"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany",
        "Partner Site Munich-Augsburg, DZPG (German Center for Mental Health), Munich, Germany"
      ],
      "name": "Sabrina Boger"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Luisa Daldrup"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Luk Eldem"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Philippa Gebhardt"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Susanne Heinrich"
    },
    {
      "affiliations": [
        "University Hospital for Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"
      ],
      "name": "Matthias Hirsmueller"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Jacob Millerowski"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany"
      ],
      "name": "Martina Richter"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany"
      ],
      "name": "Isabelle C Ridderbusch"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany"
      ],
      "name": "Svenja Suerig"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Lennart Schroeter"
    },
    {
      "affiliations": [
        "University Hospital for Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"
      ],
      "name": "Kerstin Velten-Schurian"
    },
    {
      "affiliations": [
        "Coordinating Center for Clinical Studies (KKS), University Medicine Greifswald, Greifswald, Germany"
      ],
      "name": "Stefan Engeli"
    },
    {
      "affiliations": [
        "Coordinating Center for Clinical Studies (KKS), University Medicine Greifswald, Greifswald, Germany"
      ],
      "name": "Amelie Witte"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany",
        "Partner Site Berlin, DZPG (German Center for Mental Health), Berlin, Germany"
      ],
      "name": "Malek Bajbouj"
    },
    {
      "affiliations": [
        "University Hospital for Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany",
        "Partner Site Tuebingen, DZPG (German Center for Mental Health), Tuebingen, Germany"
      ],
      "name": "Andreas J Fallgatter"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Kai G Kahl"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany"
      ],
      "name": "Tilo Kircher"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Stephan Köhler"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Alexandra Philipsen"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany"
      ],
      "name": "Martin Walter"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany",
        "Partner Site Munich-Augsburg, DZPG (German Center for Mental Health), Munich, Germany"
      ],
      "name": "Johannes Wolf"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany",
        "Translational Psychiatry Lab, University Psychiatric Clinics Basel, Basel, Switzerland"
      ],
      "name": "Anne Guhn"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany"
      ],
      "name": "Ulrich Schweiger"
    },
    {
      "affiliations": [
        "Department of Clinical Psychology and Psychotherapy, University of Dresden, Dresden, Germany"
      ],
      "name": "Jürgen Hoyer"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Dennis Gutzmer"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Stephan Mauersberger"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Selin Demir"
    },
    {
      "affiliations": [
        "Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany"
      ],
      "name": "Sarah Stapel"
    },
    {
      "affiliations": [
        "Department of Clinical Psychology and Psychotherapy, University of Greifswald, Greifswald, Germany"
      ],
      "name": "Jonas Hallgans"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany"
      ],
      "name": "Cornelius Schüle"
    },
    {
      "affiliations": [
        "University Hospital for Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"
      ],
      "name": "Christian Frischholz"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Ivo Heitland"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany"
      ],
      "name": "Stephanie Rek"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany"
      ],
      "name": "Andrea Jobst"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany"
      ],
      "name": "Ina Kluge"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany"
      ],
      "name": "Silke Lux"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany"
      ],
      "name": "Nils Opel"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany"
      ],
      "name": "Svenja Orlowski"
    },
    {
      "affiliations": [
        "University Hospital for Psychiatry and Psychotherapy, University of Tuebingen, Tuebingen, Germany"
      ],
      "name": "Christina Reinert"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Henrike Voelz"
    },
    {
      "affiliations": [
        "Research Department of Clinical, Educational and Health Psychology, University College London, London, UK"
      ],
      "name": "Isabel M Berwian"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Social Psychiatry and Psychotherapy, Medizinische Hochschule Hannover, Hannover, Germany"
      ],
      "name": "Helge Frieling"
    },
    {
      "affiliations": [
        "Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"
      ],
      "name": "Hannah B Maier"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany"
      ],
      "name": "Henrik Walter"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Psychosomatics and Psychotherapy, Lübeck University, Lübeck, Germany"
      ],
      "name": "Eva Fassbinder"
    },
    {
      "affiliations": [
        "Department of Methods and Evaluation/Quality Assurance, Free University Berlin, Berlin, Germany"
      ],
      "name": "Tim Kaiser"
    },
    {
      "affiliations": [
        "Department of Psychology, University of Washington, Seattle, Washington, USA"
      ],
      "name": "Jonathan Kanter"
    },
    {
      "affiliations": [
        "Department of Psychiatry, State University of New York, University at Buffalo, Buffalo, New York, USA"
      ],
      "name": "John Swan"
    },
    {
      "affiliations": [
        "Department of Clinical, Neuro and Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"
      ],
      "name": "Pim Cuijpers"
    },
    {
      "affiliations": [
        "Department of Psychology, Clinical Psychology, and Psychotherapy, University of Tuebingen, Tübingen, Germany"
      ],
      "name": "Martin Hautzinger"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Neurosciences, Charité Universitätsmedizin Berlin, Berlin, Germany",
        "Translational Psychiatry Lab, University Psychiatric Clinics Basel, Basel, Switzerland"
      ],
      "name": "Philipp Sterzer"
    },
    {
      "affiliations": [
        "Department of Psychiatry and Psychotherapy, University Hospital LMU Munich, Munich, Germany",
        "Partner Site Munich-Augsburg, DZPG (German Center for Mental Health), Munich, Germany"
      ],
      "name": "Frank Padberg"
    }
  ],
  "title": "Efficacy, moderators and mediators of cognitive behavioural analysis system of psychotherapy (CBASP) versus behavioural activation (BA) in persistently depressed treatment-resistant inpatients: study protocol for the multicentre, randomised controlled changePDD trial",
  "uid": "5584e9a7-de7c-5e2b-b821-7c84df25e649"
}