{
  "abstract": "Introduction Harms due to methamphetamine use disorder (MAUD) are rising globally. Untreated withdrawal symptoms perpetuate the cycle of dependence and are a barrier to treatment. There is no pharmacotherapy approved for methamphetamine withdrawal. Lisdexamfetamine (LDX) dimesylate has potential as an agonist therapy to ameliorate symptom severity during acute methamphetamine withdrawal and increase duration of initial abstinence and retention in treatment.Methods and analysis We will conduct a double-blind, randomised, controlled trial to evaluate the efficacy of LDX in reducing symptom severity during acute methamphetamine (MA) withdrawal. One hundred eighty-four adults with moderate to severe MAUD presenting to a health service requesting MA withdrawal treatment who report use of MA within the last 72 hours will be recruited. Participants will be randomised 1:1 to receive a tapering dose of lisdexamfetamine (250 mg on day 1, reducing by 50 mg per day to 50 mg on day 5, followed by 2 days of placebo washout on days 6 and 7), or placebo for 7 days. The study will be conducted over 7 days in an inpatient unit, and all participants will also receive standard inpatient withdrawal care. Participants will be followed up in the community to day 84. The primary outcome is efficacy, defined as the between-group difference in average withdrawal severity measured over the 7-day admission by the Amphetamine Withdrawal Questionnaire. Secondary outcomes are retention in treatment, treatment satisfaction, sleep and concomitant medication use (symptomatic medications and medications for other indications to day 7); safety, craving for MA, post-treatment withdrawal symptoms, depression, anxiety and stress, insomnia and cost effectiveness (to day 28) and MA use, mental, physical and social health and post-withdrawal treatment utilisation (to day 84). A First Nations qualitative substudy will assess the experiences of Aboriginal and Torres Strait Islander participants, ensuring the treatment meets the needs of First Nations people.Ethics and dissemination This protocol was first approved by the St Vincent’s Hospital Human Research Ethics Committee on 15/05/2024 (2024/ETH00788). All participants will be provided with a participant information sheet and consent form, be fully informed about the study and given ample time to consider participation. Results will be published in peer-reviewed journals and presented at national and international conferences. Findings will be presented such that individual participants will not be identifiable.Trial registration number ACTRN12624001061527.",
  "authors": [
    {
      "affiliations": [
        "National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Sydney, New South Wales, Australia",
        "Alcohol and Drug Service, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia",
        "National Drug and Alcohol Research Centre, University of New South Wales, Randwick, New South Wales, Australia"
      ],
      "name": "Liam S Acheson"
    },
    {
      "affiliations": [
        "Alcohol and Drug Service, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia",
        "National Drug and Alcohol Research Centre, University of New South Wales, Randwick, New South Wales, Australia",
        "National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Randwick, New South Wales, Australia",
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia"
      ],
      "name": "Krista J Siefried"
    },
    {
      "affiliations": [
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia",
        "South Eastern Sydney Local Health District, Sydney, New South Wales, Australia",
        "Discipline of Addiction Medicine, The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Nicholas Lintzeris"
    },
    {
      "affiliations": [
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia",
        "Hunter New England Health, Newcastle, New South Wales, Australia",
        "The University of Newcastle, Newcastle, New South Wales, Australia"
      ],
      "name": "Adrian J Dunlop"
    },
    {
      "affiliations": [
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia",
        "Discipline of Addiction Medicine, The University of Sydney, Sydney, New South Wales, Australia",
        "Drug Health Services, Sydney Local Health District, Camperdown, New South Wales, Australia"
      ],
      "name": "Paul S Haber"
    },
    {
      "affiliations": [
        "Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia",
        "Turning Point, Eastern Health, Box Hill, Victoria, Australia"
      ],
      "name": "Shalini Arunogiri"
    },
    {
      "affiliations": [
        "Next Step Drug and Alcohol Services, Perth, New South Wales, Australia",
        "National Drug Research Institute, Curtin University, Perth, Western Australia, Australia"
      ],
      "name": "Michael Christmass"
    },
    {
      "affiliations": [
        "Centre for Research Excellence in Aboriginal Health and Alcohol, Discipline of Medicine, Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia"
      ],
      "name": "Michael Doyle"
    },
    {
      "affiliations": [
        "Clinical Research Unit, UNSW Medicine & Health, Sydney, New South Wales, Australia",
        "The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "Mark Donoghoe"
    },
    {
      "affiliations": [
        "Real Drug Talk, Melbourne, Victoria, Australia"
      ],
      "name": "Jack Nagle"
    },
    {
      "affiliations": [
        "Alcohol and Drug Service, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia",
        "National Drug and Alcohol Research Centre, University of New South Wales, Randwick, New South Wales, Australia",
        "National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Randwick, New South Wales, Australia",
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia"
      ],
      "name": "Brendan Clifford"
    },
    {
      "affiliations": [
        "National Drug and Alcohol Research Centre, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "Rebecca McKetin"
    },
    {
      "affiliations": [
        "Monash Addiction Research Centre, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia",
        "Turning Point, Eastern Health, Box Hill, Victoria, Australia"
      ],
      "name": "Dan I Lubman"
    },
    {
      "affiliations": [
        "St. Vincent’s Clinical School, University of New South Wales, Sydney, New South Wales, Australia",
        "School of Population Health, University of New South Wales, Sydney, New South Wales, Australia"
      ],
      "name": "Jonathan Brett"
    },
    {
      "affiliations": [
        "Policy, Ethics, and Research, Aboriginal Health & Medical Research Council, Sydney, New South Wales, Australia"
      ],
      "name": "Nathan Taylor"
    },
    {
      "affiliations": [
        "Applied Medical Research, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia"
      ],
      "name": "Andrew Carr"
    },
    {
      "affiliations": [
        "Department of Psychiatry, Columbia University Irving Medical Center, New York State, New York, USA",
        "Division on Substance Use Disorders, New York State Psychiatric Institute, New York, New York, USA"
      ],
      "name": "Frances R Levin"
    },
    {
      "affiliations": [
        "Department of Family Medicine, University of California Los Angeles, Los Angeles, California, USA"
      ],
      "name": "Steven Shoptaw"
    },
    {
      "affiliations": [
        "National Centre for Clinical Research on Emerging Drugs, University of New South Wales, Sydney, New South Wales, Australia",
        "Alcohol and Drug Service, St Vincent’s Hospital Sydney, Darlinghurst, New South Wales, Australia",
        "National Drug and Alcohol Research Centre, University of New South Wales, Randwick, New South Wales, Australia",
        "Drug and Alcohol Clinical Research and Improvement Network, NSW Health, St Leonards, New South Wales, Australia"
      ],
      "name": "Nadine Ezard"
    }
  ],
  "title": "Study protocol for a randomised controlled trial to determine the efficacy of lisdexamfetamine for the treatment of acute methamphetamine withdrawal in inpatient settings",
  "uid": "dc4a1ee4-cba7-59bd-a066-4c68b041cd88"
}