Explaining differential effects of medication for opioid use disorder using a novel approach incorporating mediating variables.

Abstract

A recent study found that homeless individuals with opioid use disorder (OUD) had a lower risk of relapse on extended-release naltrexone (XR-NTX) versus buprenorphine-naloxone (BUP-NX), whereas non-homeless individuals had a lower risk of relapse on BUP-NX. This secondary study examined differences in mediation pathways to medication effect between homeless and non-homeless participants. Secondary analysis of an open-label randomized controlled, 24-week comparative effectiveness trial, 2014-17. Eight community addiction treatment programs in the United States. English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n=570). Randomization to monthly injection of XR-NTX or daily sublingual BUP-NX. Mediation analysis estimated the direct effect of XR-NTX versus BUP-NX on relapse and indirect effect through mediators of medication adherence, use of illicit opioids, depressive symptoms and pain, separately by homeless status. For the homeless subgroup, the protective indirect path contributed a 3.4 percentage point reduced risk of relapse [95% confidence interval (CI)=-12.0, 5.3] comparing XR-NTX to BUP-NX (explaining 21% of the total effect). For the non-homeless subgroup, the indirect path contributed a 9.4 percentage point increased risk of relapse (95% CI=3.1, 15.7) comparing XR-NTX to BUP-NX (explaining 57% of the total effect). A novel approach to mediation analysis shows that much of the difference in medication effectiveness (extended-release naltrexone versus buprenorphine-naloxone) on opioid relapse among non-homeless adults with opioid use disorder appears to be explained by mediators of adherence, illicit opioid use, depressive symptoms and pain.