{
  "abstract": "Introduction Bipolar disorder affects around 2% of the population and is linked with reduced life expectancy and socioeconomic burden. Depressive episodes are difficult to treat and typically more prevalent, enduring and burdensome than manic episodes. The use of antidepressants alone has limited effect and is associated with significant clinical risk through polarity switch. Current National Institute for Health and Care Excellence guidelines recommend quetiapine, olanzapine (with or without fluoxetine) and lamotrigine; however, these medications have limited efficacy, tolerability and acceptability. The ASCEnD study aims to assess the clinical and cost-effectiveness of aripiprazole plus sertraline compared with quetiapine, offering potential improvements for outcomes in bipolar depression. The study is funded by the National Institute for Health and Care Research Health Technology Assessment programme (NIHR132773).Methods and analysis ASCEnD is a prospective, two-arm, superiority, individually 1:1 randomised, controlled, pragmatic, parallel group, type A open-label clinical trial of aripiprazole/sertraline medication combination compared with quetiapine for bipolar depression. The study is conducted in the UK National Health Service setting with the aim of recruiting and randomising 270 participants followed-up for 24 weeks. Adults with bipolar disorder self-refer or are recruited through primary and secondary care services. The primary outcome is change in depressive symptoms 12–16 weeks after randomisation. Secondary outcomes include measures of symptom change, treatment satisfaction, tolerability, medication adherence, concomitant medication use, psychosocial functioning, quality of life and cost-effectiveness and informal carer measures of quality of life and costs of caring. The exploratory outcome is change in participant reward and punishment responsiveness. Analysis will follow a prespecified statistical analysis plan. A nested qualitative study is included to examine feasibility and acceptability of the trial design.Ethics and dissemination A Clinical Trial Authorisation from Medicines and Healthcare products Regulatory Agency, and approval from the Health Research Authority (IRAS 1007468) and North East – Newcastle and North Tyneside 1 Research Ethics Committee (23/NE/0132) were obtained. Results will be disseminated through peer-reviewed publications, conference presentations and lay summaries for participants and patient and public groups.Trial registration number ISRCTN63917405.",
  "authors": [
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Lumbini Azim"
    },
    {
      "affiliations": [
        "Biostatistics Research Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Sarah Al-Ashmori"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Chrissie Butcher"
    },
    {
      "affiliations": [
        "Oxford Health NHS Foundation Trust, Oxford, UK",
        "University of Oxford Department of Psychiatry, Oxford, UK"
      ],
      "name": "Andrea Cipriani"
    },
    {
      "affiliations": [
        "Keele University School of Medicine, Keele, UK"
      ],
      "name": "Carolyn A Chew-Graham"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK"
      ],
      "name": "Emily Clare"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Emma Clark"
    },
    {
      "affiliations": [
        "Biostatistics Research Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Michael Cole"
    },
    {
      "affiliations": [
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Susanna Carella"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK"
      ],
      "name": "Lyndsey Dixon"
    },
    {
      "affiliations": [
        "Avon and Wiltshire Mental Health Partnership NHS Trust, Bath, UK",
        "Bristol Medical School, Bristol, UK"
      ],
      "name": "Jonathan Evans"
    },
    {
      "affiliations": [
        "Bipolar UK, University College London Division of Psychiatry, London, UK",
        "Cardiff University Division of Psychological Medicine and Clinical Neurosciences, Cardiff, UK"
      ],
      "name": "Tania Gergel"
    },
    {
      "affiliations": [
        "The McPin Foundation, London, UK"
      ],
      "name": "John Gibson"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Helen C Hancock"
    },
    {
      "affiliations": [
        "Keele University School of Medicine, Keele, UK"
      ],
      "name": "Isobel Hoppe"
    },
    {
      "affiliations": [
        "Bristol Medical School, Bristol, UK"
      ],
      "name": "David Kessler"
    },
    {
      "affiliations": [
        "University of Oxford Department of Psychiatry, Oxford, UK"
      ],
      "name": "Thomas Kabir"
    },
    {
      "affiliations": [
        "University College London Division of Psychiatry, London, UK"
      ],
      "name": "Glyn Lewis"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Ayesha Mathias"
    },
    {
      "affiliations": [
        "Mental Health and Clinical Neurosciences, University of Nottingham School of Medicine, Nottingham, UK",
        "Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, UK"
      ],
      "name": "Richard Morris"
    },
    {
      "affiliations": [
        "Mental Health and Clinical Neurosciences, University of Nottingham School of Medicine, Nottingham, UK",
        "Nottinghamshire Healthcare NHS Foundation Trust, Nottingham, UK"
      ],
      "name": "Neil Nixon"
    },
    {
      "affiliations": [
        "University of Oxford Department of Psychiatry, Oxford, UK",
        "Medical University of Vienna Department of Health Economics, Vienna, Austria"
      ],
      "name": "Judit Simon"
    },
    {
      "affiliations": [
        "Biostatistics Research Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Marion Dawn Teare"
    },
    {
      "affiliations": [
        "The McPin Foundation, London, UK"
      ],
      "name": "The Lived Experience Advisory Panel"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Mourad Wahba"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Lauren Wall"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Zoe Walmsley"
    },
    {
      "affiliations": [
        "Medical University of Vienna Department of Health Economics, Vienna, Austria"
      ],
      "name": "Dennis Wienand"
    },
    {
      "affiliations": [
        "Newcastle Clinical Trials Unit, Newcastle upon Tyne, UK"
      ],
      "name": "Faye Wolstenhulme"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Niraj Ahuja"
    },
    {
      "affiliations": [
        "Cumbria Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK",
        "Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK"
      ],
      "name": "Stuart Watson"
    }
  ],
  "title": "Open-label randomised controlled trial of aripiprazole/sertraline combination in comparison with quetiapine for the clinical and cost-effectiveness of treatment of bipolar depression (the ASCEnD study): study protocol",
  "uid": "f0637952-ff50-5c7e-bc8d-6942cf7d2a38"
}