# Risk of opioid overdose during buprenorphine treatment for opioid use disorder in the fentanyl era

## TL;DR

This study finds that buprenorphine treatment remains effective at preventing opioid overdoses, even in the fentanyl era, and higher doses do not increase overdose risk.

## Contribution

The study provides evidence that buprenorphine remains effective for overdose prevention in the fentanyl era and refutes concerns about higher doses increasing risk.

## Key findings

- Opioid overdose risk was 61% lower on days with an active buprenorphine prescription.
- There was no evidence that higher buprenorphine doses were associated with increased overdose risk.
- 52.6% of person-days were covered by an active buprenorphine prescription during the study period.

## Abstract

For patients who use fentanyl, higher than currently recommended
maintenance doses of buprenorphine treatment for opioid use disorder (OUD)
may be needed to prevent cravings and withdrawal, but some clinicians and
regulators are concerned that higher doses may increase overdose risk. We
evaluated buprenorphine effectiveness for overdose prevention in the
fentanyl era.

We conducted a retrospective cohort study of Rhode Island residents
initiating buprenorphine for OUD (October 2016‒September 2022) using
statewide administrative data. On each of 365 follow-up days, patients were
classified as having an active buprenorphine prescription (yes/no) and a
non-fatal or fatal opioid overdose (yes/no). Follow-up was discontinued if
patients died or initiated methadone or naltrexone. Generalized estimating
equations compared opioid overdose risk for days with versus without an
active buprenorphine prescription, controlling for potential confounders and
clustering by patient.

Among 8,676 patients initiating buprenorphine, most were aged
25–44 years (56.0 %) and male (61.3 %). In the 365 days following
initiation, 52.6 % of person-days were covered by an active buprenorphine
prescription, 1,069 patients (12.3 %) had follow-up discontinued due to
methadone initiation, and 411 patients (4.7 %) experienced 545 opioid
overdoses. Opioid overdose risk was 61 % lower for days with versus without
an active buprenorphine prescription (adjusted risk ratio = 0.39, 95 %
confidence interval = 0.31–0.49). Daily doses prescribed on days with
and without an opioid overdose event were similar (P = 0.261).

Buprenorphine remains effective for overdose prevention in the
fentanyl era among patients who remain in treatment. There was no evidence
that higher doses were associated with greater overdose risk.