Comparative efficacy of naltrexone-accelerated versus sublingual buprenorphine in opioid withdrawal management and initiating injectable naltrexone treatment: study protocol for a randomized controlled trial.
- 1Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- 2Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran.
Abstract
Background
Extended-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
This 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
The 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
https://en.irct.ir/trial/81525, Iranian Registry of Clinical Trials IRCT20250123064499N1.
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BibTeX
@article{jafari2026comparative,
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.}},
author = {Saeede Jafari and Afarin Rahimi-Movaghar and Alireza Noroozi and Pooneh Malekifar and Akbar Fotouhi},
journal = {Frontiers in psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1933443},
url = {https://europepmc.org/article/MED/42909039},
note = {CC BY},
}
RIS
TY - JOUR
TI - Comparative efficacy of naltrexone-accelerated versus sublingual buprenorphine in opioid withdrawal management and initiating injectable naltrexone treatment: study protocol for a randomized controlled trial.
AU - Saeede Jafari
AU - Afarin Rahimi-Movaghar
AU - Alireza Noroozi
AU - Pooneh Malekifar
AU - Akbar Fotouhi
PY - 2026
DA - 2026/10/07
JO - Frontiers in psychiatry
DO - 10.3389/fpsyt.2026.1933443
UR - https://europepmc.org/article/MED/42909039
AB - Background Extended-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 This 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 The 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 https://en.irct.ir/trial/81525, Iranian Registry of Clinical Trials IRCT20250123064499N1.
SN - 1664-0640
ER -