{
  "abstract": "Introduction Antidepressant overprescribing and unnecessary long-term use are common and can increase the risk of adverse effects and withdrawal symptoms on discontinuation. Although gradual tapering strategies have been proposed, empirical evidence from randomised trials is lacking. This study will compare the efficacy of two antidepressant discontinuation strategies—linear and hyperbolic tapering—in adults with remitted depressive disorders.Methods and analysis This pragmatic, multicentre, open-label, parallel-group superiority randomised controlled trial will recruit adults (≥18 years) with remitted depressive disorders who have been taking an antidepressant for at least 6 months. During an 8-month recruitment period, participants in outpatient psychiatric and primary care settings will be randomised (1:1) to (a) linear tapering (dose reduced by 50% of the minimum effective dose every 2 weeks until cessation) or (b) hyperbolic tapering (dose reduced by 20–25% every 2 weeks until cessation). The primary outcome is the proportion of participants who fail to discontinue the antidepressant by the end of the predefined tapering schedule or who re-initiate antidepressant therapy within 16 weeks of discontinuation. Secondary outcomes include safety, tolerability (including withdrawal symptoms), acceptability, clinical effectiveness, social functioning, quality of life and cost-effectiveness. Recruiters and participants will be aware of their treatment allocation; however, outcome assessors and the biostatistician will remain blinded throughout follow-up. Validated rating scales measuring depression, anxiety, withdrawal symptoms and social functioning will be administered at baseline and at scheduled follow-up visits up to 36 weeks. Based on observational data, we aim to recruit 150 participants (75 per arm).Ethics and dissemination The study was approved by institutional Ethics Committees and regulatory authorities. Written informed consent will be obtained from all participants and data processed in accordance with General Data Protection Regulation. Study insurance and pharmacovigilance procedures are in place. Findings will be published in open-access journals, presented at scientific meetings and communicated to policy and regulatory stakeholders.Trial registration NCT07393919.",
  "authors": [
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Giovanni Ostuzzi"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Chiara Gastaldon"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Debora Zaccoletti"
    },
    {
      "affiliations": [
        "School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy",
        "Department of Mental Health, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Lombardy, Italy"
      ],
      "name": "Francesco Bartoli"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Giulia Belnome"
    },
    {
      "affiliations": [
        "School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy",
        "Department of Mental Health, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Lombardy, Italy"
      ],
      "name": "Giuseppe Carrà"
    },
    {
      "affiliations": [
        "Department of Mental Health and Addiction, ASST Santi Paolo e Carlo, Milan, Italy"
      ],
      "name": "Simone Cavallotti"
    },
    {
      "affiliations": [
        "Department of General Psychology, University of Padua, Padua, Italy"
      ],
      "name": "Ioana Cristea"
    },
    {
      "affiliations": [
        "Department of Mental Health and Addiction, ASST Santi Paolo e Carlo, Milan, Italy",
        "Department of Health Sciences, University of Milan, Milan, Italy"
      ],
      "name": "Armando D’Agostino"
    },
    {
      "affiliations": [
        "Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy"
      ],
      "name": "Pasquale De Fazio"
    },
    {
      "affiliations": [
        "Department of Health Sciences, Magna Graecia University of Catanzaro, Catanzaro, Italy"
      ],
      "name": "Renato de Filippis"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Carolina Gottardi"
    },
    {
      "affiliations": [
        "Department of General Psychology, University of Padua, Padua, Italy"
      ],
      "name": "Caterina Novara"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Davide Papola"
    },
    {
      "affiliations": [
        "School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy",
        "Department of Mental Health, IRCCS San Gerardo dei Tintori Foundation Hospital, Monza, Lombardy, Italy"
      ],
      "name": "Ilaria Riboldi"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Federico Tedeschi"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Francesco Amaddeo"
    },
    {
      "affiliations": [
        "WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neurosciences, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy"
      ],
      "name": "Corrado Barbui"
    }
  ],
  "title": "Safe discontinuation of antidepressants in individuals with clinically remitted depressive disorders: study protocol for a randomised controlled trial",
  "uid": "8a2038d0-d9bf-5716-a5ab-88b7357a6a75"
}