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

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, whereas non-homeless individuals had a lower risk of relapse on BUP-NX. This secondary analysis of data from CTN-0051 (X:BOT) examined differences in mediation pathways to medication effect between homeless and non-homeless participants. The X:BOT trial was an open-label randomized controlled, 24-week comparative effectiveness trial held in 8 community addiction treatment programs in the U.S. Participants were English-speaking adults with DSM-5 OUD, recruited during inpatient admission (N=570) and then randomized to monthly injection of XR-NTX or daily sublingual BUP-NX.

In this secondary analysis, 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, analysis found that the protective indirect path contributed a 3.4 percentage point reduced risk of relapse 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 comparing XR-NTX to BUP-NX (explaining 57% of the total effect).

Conclusions: A novel approach to medication analysis shows that much of the difference in medication effectiveness (XR-NTX versus BUP-NX) 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.

Related protocols: CTN-0051