Repeated-dose behavioral intervention to reduce opioid overdose among overdose survivors with opioid use disorder: A two-site phase III randomized controlled trial

Abstract

Background and aims: The emergence of fentanyl in the street market for opioids has limited the benefits of some interventions to manage opioid overdose; thus, preventing the occurrence of opioid overdose is essential. We tested a behavioral intervention shown to prevent heroin overdose in a pilot study, in two United States cities with prevalent fentanyl.

Design: Phase III two-site single-blinded randomized controlled trial of a repeated dose motivational interviewing intervention to reduce overdose (REBOOT) versus attention control, over 16 months from 2019 to 2023.

Setting: San Francisco, California, and Boston, Massachusetts, USA.

Participants: 18-65 years of age, with opioid use disorder (OUD), active non-prescribed opioid use, opioid overdose within 3 years and prior receipt of take-home naloxone. A total of 268 participants were randomized (50% intervention, 50% control), 62% of whom were male, 15% Latine, 65% White and 14% Black/African American; 95% had used fentanyl.

Intervention: Motivational interviewing review of experienced and witnessed overdose and development of personal prevention plan, administered at months 0, 4, 8 and 12.

Measurements: TimeLine FollowBack of interval overdose events and covariates, administered prior to the intervention at months 0, 4, 8, 12 and 16. Primary outcome was occurrence of any nonfatal or fatal overdose event.

Findings: There were no significant effects of REBOOT compared with control on the primary outcome of occurrence of any overdose [relative risk (RR) = 0.94, 95% confidence interval (CI) = 0.79-1.11, P = 0.45] or secondary outcome of the number of overdose events (RR = 0.80, 95% CI = 0.6-1.06, P = 0.12). Results did not differ when excluding data collected during the first 12 months of the COVID-19 pandemic. Compared with control, REBOOT was not associated with days in OUD treatment and not using opioids (RR = 0.94, 95% CI = 0.88-1.00, P = 0.06). In post-hoc analysis, REBOOT was associated with fewer overdose events among participants with no past 4-month overdose at baseline (RR = 0.70, 95% CI = 0.51-0.97, P = 0.03).

Conclusion: A repeated dose motivational interviewing intervention to reduce overdose had no statistically significant effect on opioid overdose in two US cities where fentanyl was the dominant street opioid.

Keywords: Boston and San Francisco; behavioral intervention; fentanyl; motivational interviewing; opioid overdose; randomized controlled trial.