Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism.

Extended-release formulations of naltrexone have emerged as effective treatment options for opioid use disorder. This post-hoc analysis examined the temporal relationship between episodes of opioid use and subsequent dropout in a placebo-controlled trial of extended-release injection naltrexone (XR-NTX) to draw inferences about the mechanism by which extended blockade of opioid receptors translates into clinical effectiveness. This was a 24-week multiple-site, double-blind, randomized trial of monthly XR-NTX versus placebo injections. We analyzed time to dropout from treatment using survival analysis with an extended Cox model as a function of treatment (XR-NTX versus placebo) and with weekly urine drug test (UDT) results for opioids at each week as a time-dependent covariate. Thirteen addiction treatment programs in Russia, 2008-09. A total of 250 adults with opioid use disorder who had completed in-patient detoxification. XR-NTX injection or placebo injection every 4 weeks with weekly clinic visits and biweekly counseling. Urine toxicology for opioids measured weekly and week of dropout from treatment. The Cox model yielded a significant interaction of time-dependent urine toxicology by treatment (P = 0.024). Among patients receiving placebo, a positive UDT in a given week increased the risk for dropout from treatment in the subsequent week [hazard ratio (HR) = 6.25; 95% confidence interval (CI) = 3.6-10.0], whereas among patients receiving XR-NTX, a positive UDT result showed no significant effect on risk for dropout (HR = 1.67; 95% CI = 0.6-4.5). The proportion of patients who completed all 24 weeks without any positive UDT result was 31% on XR-NTX compared with 20% on placebo (P = 0.051). Extended-release injection naltrexone was effective at reducing the risk of dropout from opioid use disorder treatment after an episode of opioid use. Just under a third of patients (31%) on XR-NTX had no opioid-positive urine tests across the trial, but the hypothesis that this would differ from placebo (20%) was not confirmed. © 2019 Society for the Study of Addiction.

Citation

Edward V Nunes, Adam Bisaga, Evgeny Krupitsky, Narinder Nangia, Bernard L Silverman, Sarah C Akerman, Maria A Sullivan. Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism. Addiction (Abingdon, England). 2020 Feb;115(2):239-246

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PMID: 31313402

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