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Explaining differential effects of medication for opioid use disorder using a novel approach incorporating mediating
Kara E Rudolph1, Iván Díaz2, Nima S Hejazi3
1Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Background And Aims:
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.
Design:
Secondary analysis of an open-label randomized controlled, 24-week comparative effectiveness trial, 2014-17.
Setting:
Eight community addiction treatment programs in the United States.
Participants:
English-speaking adults with DSM-5 OUD, recruited during inpatient admission (n = 570).
Intervention(S):
Randomization to monthly injection of XR-NTX or daily sublingual BUP-NX.
Measurements(S):
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.
Findings:
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).
Conclusions:
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.
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