Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: a randomized controlled trial

Abstract

Background: Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults.

Methods: Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections.

Results: Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002).

Conclusions: Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use.

Trial registration: ClinicalTrials.gov NCT00684788.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

The percentage of XR-NTX doses accepted by participants in the prescription and contingency conditions. Bars show condition percentages and circles show individual percentages.

Figure 2

The percentage of participants retained in XR-NTX treatment (continued to take scheduled injections; top panel) and the therapeutic workplace (continued attending the workplace; bottom panel) across study weeks.

Figure 3

Naltrexone blockade and opiate and cocaine urinalysis results across consecutive thrice weekly urine samples collected when participants attended the therapeutic workplace. Within each panel, rows of data represent the results for individual participants. Urinalysis results are based on samples collected three times per week, typically on Monday, Wednesday and Friday of each week. Samples prior to the left of the vertical black line at 0 on the horizontal axis were collected prior to random assignment while participants were taking oral naltrexone. Black squares indicate urine samples negative for both opiates and cocaine; orange squares indicate opiate positive urine samples; white squares with crosses indicate cocaine positive urine samples; orange squares with crosses indicate samples positive for both opiates and cocaine. Empty sections indicate missing samples. Shaded portions show when participants were blocked by naltrexone (i.e., the sample was collected within 4 weeks of the last naltrexone injection). Vertical lines after urine samples 0, 12, 24, 36, 48, and 60 indicate the time of scheduled injections. Within each panel, participants are arranged from top to bottom from those with the most to least naltrexone blockade, most to least opiate negative samples, and then most to least cocaine negative samples.