{
  "abstract": "Introduction Depression is the dominant phase in bipolar disorder, but the available treatments are scarce. Lithium is a first-line option in several guidelines despite limited evidence, whereas cariprazine has a well-documented efficacy for depressive episodes. By comparing lithium and cariprazine in terms of efficacy and tolerability, we aim to contribute to an evidence-based positioning of lithium in future guidelines.Methods and analysis An open label, randomised, multicentre, investigator-sponsored comparison of lithium versus cariprazine with a treatment duration of 8 weeks. Participants are aged 18–65 years and are suffering from a depressive episode as part of bipolar disorder, type 1 or 2. The primary outcome is the difference between the two groups in change from baseline to endpoint on Hamilton depression scale, 6 item version, based on the modified intention-to-treat population. Continuous variables will be analysed by using two-sided t-tests and mixed effects models. For categorical measures, χ 2 tests and multivariable models will be applied. Secondary outcomes include AEs and measures of well-being, depressive, manic and suicidal symptoms, as well as cognitive function. The study is powered as a superiority trial, with a calculated study population of 122 participants.Ethics and dissemination Protocol has been approved by the regional ethical committee N-20220007 and European Medicines Agency. All participants provide written informed consent. The protocol was written according to Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines. Results will be disseminated in peer-reviewed international journals.Trial registration number EU-CTR, 2024-517170-20-01; NCT05913947.",
  "authors": [
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark",
        "Department of Clinical Medicine, Aalborg University, Aalborg, Denmark"
      ],
      "name": "Sanne Vendelbo Hovgesen"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark",
        "Department of Clinical Medicine, Aalborg University, Aalborg, Denmark"
      ],
      "name": "Rasmus W Wentzer Licht"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aarhus University Hospital, Aarhus, Denmark"
      ],
      "name": "Sune Puggaard Vogt Straszek"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark"
      ],
      "name": "Ann-Eva Christensen"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark",
        "The Early Multimodular Prevention and Intervention Research Institution (EMPIRI), Capital Region of Denmark Mental Health Services, Hillerød, Denmark"
      ],
      "name": "Maj Vinberg"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark",
        "Centre for Neuropsychiatric Depression Research (CNDR), Psychiatric Centre Glostrup, Capital Region of Denmark Mental Health Services, Copenhagen, Denmark"
      ],
      "name": "Poul Videbech"
    },
    {
      "affiliations": [
        "Neurocognition and Emotion Across Disorders of the Brain Centre (NEAD), Capital Region of Denmark Mental Health Services, Frederiksberg, Denmark",
        "Department of Psychology, University of Copenhagen, Copenhagen, Denmark"
      ],
      "name": "Kamilla Woznica Miskowiak"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark"
      ],
      "name": "Simon Johnsen"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark"
      ],
      "name": "Mette Marcus Munk"
    },
    {
      "affiliations": [
        "Department of Mental Health Odense-Svendborg, Odense University Hospital, Odense, Denmark"
      ],
      "name": "Manuel Linnart Mai"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany"
      ],
      "name": "Christopher Baethge"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark",
        "Copenhagen Affective disorder Research Center (CADIC), Capital Region of Denmark Mental Health Services, Copenhagen, Denmark"
      ],
      "name": "Lars Vedel Kessing"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Aalborg University Hospital, Aalborg, Denmark",
        "Department of Clinical Medicine, Aalborg University, Aalborg, Denmark"
      ],
      "name": "Rene Ernst Nielsen"
    }
  ],
  "title": "Lithium versus cariprazine in the acute phase treatment for depressive episodes in patients with bipolar disorder: a protocol for a pragmatic open, randomised multicentre study – the 9th trial of the Danish University Antidepressant Group, DUAG-9",
  "uid": "d6bcee42-f995-5e0b-b6fb-15be9d501c79"
}