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Published on: January 29, 2017
Beneficial effects of the rapid vs. standard procedure for injection naltrexone initiation operate through increased
Kara E Rudolph1, Shodai Inose1, Nicholas T Williams1
1Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, United States of America.
Objective:
To estimate the extent to which increased use of clonidine and benzodiazepines is associated with the beneficial effect of the rapid versus standard procedure for induction onto extended-release injectable naltrexone (XR-NTX).
Methods:
We conducted two mediation analyses using a doubly robust nonparametric estimation approach. First, we estimated the extent to which the difference in XR-NTX initiation rates comparing the rapid vs. standard induction operated through: (1) differences in categorized daily doses of clonidine and benzodiazepines averaged over the first 3 days of the study, and (2) differences in categorized clonidine and benzodiazepine usage during each of the first 5 days, treated as time-varying mediators, and accounting for time-varying confounders and competing events.
Results:
Rapid vs. standard induction increased the probability of initiating XR-NTX by day 14 by an estimated 42.4 percentage points (95% CI: 34.6, 50.2), and the natural indirect effect (i.e., mediated effect) through clonidine and benzodiazepine use was associated with a 24.2 percentage point (95% CI: 10.3, 38.0) increased the initiation probability, explaining 57.1% of the total effect. Estimates were similar in the longitudinal mediation analysis.
Conclusions:
Use of clonidine and benzodiazepines proactively and at higher dosages during the initial days of inpatient medically managed withdrawal, in conjunction with attentive safety monitoring, could improve XR-NTX initiation rates as part of a rapid induction procedure.
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