TY - JOUR
T1 - Extended-release naltrexone for youth with opioid use disorder
AU - Mitchell, Shannon Gwin
AU - Monico, Laura B.
AU - Gryczynski, Jan
AU - Fishman, Marc J.
AU - O'Grady, Kevin E.
AU - Schwartz, Robert P.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number 5R01DA033391-05 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Dr. Schwartz has consulted for Verily Life Sciences. He is Principal Investigator of a NIDA-funded study that will be receiving free medication from Indivior and Alkermes. Dr. Monico received research funding from Indivior. Dr. Gryczynski is part owner of COG Analytics and has received research funding (paid to his institution and including project-related salary support) from Indivior. Dr. Fishman has been a consultant for Alkermes, Verily Life Sciences, Drug Delivery LLC and US World Meds, and has received research funding from Alkermes and US World Meds. Drs. Mitchell and O'Grady report no conflicts.
Publisher Copyright:
© 2021
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Adolescent
KW - Extended-release naltrexone
KW - Naltrexone
KW - Opioid use disorder
KW - Treatment
KW - Young adult
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U2 - 10.1016/j.jsat.2021.108407
DO - 10.1016/j.jsat.2021.108407
M3 - Article
C2 - 34118699
AN - SCOPUS:85104464155
SN - 0740-5472
VL - 130
JO - Journal of Substance Abuse Treatment
JF - Journal of Substance Abuse Treatment
M1 - 108407
ER -