Patient characteristics associated with successful initiation of extended-release naltrexone in the X:BOT trial.

Background and aim: Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial.

Methods: Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success.

Results: 204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89).

Conclusions: Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.

Related protocols: CTN-0051

Categories: Chronic pain, CTN platform/ancillary study, Homeless persons, Naltrexone, Opioid use disorder
Tags: Article (Peer-Reviewed)
Authors: Potter, Kenzie; Greiner, Miranda; Shulman, Matisyahu; Scodes, Jennifer; Choo, Tse-Hwei; Pavlicova, Martina; Novo, Patricia; Fishman, Marc; Lee, Joshua D.; Rotrosen, John; Nunes, Edward V.
PMID: 41928686
Source: Substance Use & Misuse 2026 (in press). [doi: 10.1080/10826084.2026.2617963]