Extended-release naltrexone for youth with opioid use disorder.

Background: Few published research studies have examined the effectiveness of extended-release naltrexone (XR-NTX) for the treatment of opioid use disorder (OUD) among adolescents and young adults.

Methods: This two-group randomized controlled trial recruited 288 youth, ages 15-21, with moderate/severe OUD from a residential addiction treatment program in Baltimore, Maryland. The study randomized the youth within the first week of treatment entry to receive either XR-NTX or treatment-as-usual (TAU; either buprenorphine maintenance treatment or treatment without OUD medication following medically managed withdrawal) prior to discharge, with continued treatment in the community for 6 months. However, due to various reasons spanning patients' and caregivers' preferences and constraints, considerable participant nonadherence to randomized condition occurred (i.e., only 30% of the participants randomized to XR-NTX received an initial injection, while 27% of participants randomized to TAU received an XR-NTX injection at treatment discharge, instead of their assigned treatment). The study used generalized linear mixed modeling (GLiMM) to examine self-reported 90-day opioid, cocaine, marijuana, and alcohol use as well as DSM-5 OUD criteria on "intention-to-treat" (as randomized), "as-received" (XR-NTX vs. not XR-NTX), and "as-medicated" (XR-NTX vs. buprenorphine vs. no medication) bases.

Results: The condition x time interactions in the intention-to-treat analyses failed to reach significance for past-90-day self-reported use of illicit opioids, cocaine, marijuana, or alcohol, or in meeting DSM-5 OUD criteria at 3 or 6 months [all ps > 0.05]. However, these findings are of limited interpretive value due to participant nonadherence to their randomized condition. When the study analyzed results by the treatment received at discharge, the "as-received" group x time interaction for illicit opioid use was significant [p = .003], with the XR-NTX group reporting less opioid use in the past 90 days at 3 and 6 months. Participants who received their first XR-NTX dose at inpatient discharge (n = 82) received, on average, 1.3 subsequent injections in the community over the 6-month study follow-up period. Only 2 of the 82 study participants received XR-NTX continuously through the 6-month postdischarge follow-up period. Twelve serious adverse events (SAEs) occurred during the study, but the study determined that only 1 was possibly study related (hepatitis C/elevated liver function test results).

Conclusion: None of the condition x time interactions in the intention-to-treat analyses reached significance. Participants' nonadherence may have contributed to the failure to reject the null hypothesis. Irrespective of randomized condition, participants who received XR-NTX for OUD demonstrated low retention in treatment, receiving an average of only 1.3 subsequent injections, yet reported less opioid use at follow-up than participants who did not received XR-NTX. Treatment programs should consider XR-NTX as a treatment option for youth motivated to receive it. Future research should focus on building developmentally informed strategies to improve uptake of and adherence to relapse prevention medication in this population.