{
  "abstract": "Background\n\nExtended-release injectable naltrexone (XR-NTX), a long-acting opioid antagonist, is an effective relapse prevention strategy in the treatment of opioid use disorder (OUD). However, standard XR-NTX initiation requires completion of opioid withdrawal management and a 1-2 week opioid-free period. This interval is associated with heightened vulnerability to lapse and relapse, and many patients fail to initiate XR-NTX treatment successfully. Therefore, alternative strategies that enable rapid XR-NTX initiation are needed. This study aimed to compare the effectiveness and safety of naltrexone-accelerated (NA) versus sublingual buprenorphine (SB) withdrawal management in facilitating XR-NTX initiation among patients with OUD.Methods\n\nThis single-center, open-label, randomized controlled trial uses a parallel-group design. Eligible patients aged 18-60 years with moderate to severe OUD who are actively using opioids and are not receiving regular maintenance treatment with methadone or buprenorphine are randomly assigned to one of two groups: (1) NA withdrawal management, comprising one day of adjunctive non-opioid medications, one day of buprenorphine administration, one day of washout, and four days of gradual oral naltrexone titration (1, 3, 12, and 25 mg/day); or (2) SB withdrawal management, comprising one day of adjunctive non-opioid medications, six days of buprenorphine tapering (up to 8 mg on Day 2, 6 mg on Day 3, 4 mg on Days 4-5, 2 mg on Day 6, and 1 mg on Day 7), and a seven-day washout period. Adjunctive non-opioid medications in both groups comprised clonidine, clonazepam, gabapentin, and trazodone. The primary outcomes are the proportions of participants who (1) achieve a negative urine drug test for the assessed opioids and (2) receive XR-NTX at the end of the withdrawal management period. Secondary outcomes include severity of withdrawal symptoms, opioid craving intensity, and adverse effects. All analyses are conducted according to the intention-to-treat principle.Discussion\n\nThe findings of this trial may provide clinically relevant evidence to support rapid initiation of XR-NTX treatment in patients with OUD and inform clinical practice.Clinical trial registration\n\nhttps://en.irct.ir/trial/81525, Iranian Registry of Clinical Trials IRCT20250123064499N1.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.",
    "Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Saeede Jafari"
    },
    {
      "affs": [
        1
      ],
      "name": "Afarin Rahimi-Movaghar"
    },
    {
      "affs": [
        1
      ],
      "name": "Alireza Noroozi"
    },
    {
      "affs": [
        1
      ],
      "name": "Pooneh Malekifar"
    },
    {
      "affs": [
        0
      ],
      "name": "Akbar Fotouhi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zm8dng0z8pbq.bib",
  "cited_by": 0,
  "doi": "10.3389/fpsyt.2026.1933443",
  "fulltext_url": "https://europepmc.org/articles/PMC13683708",
  "id": "8zm8dng0z8pbq",
  "issns": [
    "1664-0640"
  ],
  "landing_url": "https://europepmc.org/article/MED/42909039",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2739|Opioid Use Disorder Treatment"
    ]
  ],
  "openalex": "W7220837349",
  "pdf_url": "https://europepmc.org/articles/PMC13683708?pdf=render",
  "pmcid": "PMC13683708",
  "pmid": "42909039",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8zm8dng0z8pbq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "MED:42909039",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42909039"
    },
    {
      "first_seen": "2026-10-30T12:20:18Z",
      "native_id": "10.3389/fpsyt.2026.1933443",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1933443/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2739|Opioid Use Disorder Treatment",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Comparative efficacy of naltrexone-accelerated versus sublingual buprenorphine in opioid withdrawal management and initiating injectable naltrexone treatment: study protocol for a randomized controlled trial.",
  "title_text": "Comparative efficacy of naltrexone-accelerated versus sublingual buprenorphine in opioid withdrawal management and initiating injectable naltrexone treatment: study protocol for a randomized controlled trial.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:18Z",
  "url": "https://research.draconitic.com/paper/8zm8dng0z8pbq",
  "venue": "Frontiers in psychiatry",
  "versions": []
}