Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study

Abstract

Background: Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known.

Objective: To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality.

Design: Retrospective cohort study.

Setting: 7 individually linked data sets from Massachusetts government agencies.

Participants: 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014.

Measurements: Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality.

Results: In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified.

Limitation: Few events among naltrexone recipients preclude confident conclusions.

Conclusion: A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality.

Primary funding source: National Center for Advancing Translational Sciences of the National Institutes of Health.

Figure 1.. MOUD exposure classification.

For the primary classification (with discontinuation), MOUD exposure extends through the month after discontinuation (light and dark-green months). For the secondary classification (on treatment), exposure is limited to months in which treatment is received (light-green months only). In the illustrative examples, participant 1 is not exposed to MOUD through follow-up; participant 2 is exposed in months 1–2 and 7–12 for the primary classification and months 1 and 7–12 for the secondary classification. In the month of death, participant 3 would be considered exposed in the primary classification only, participant 4 would be considered exposed in both primary and secondary exposure classifications, and participant 5 would be considered not exposed to MOUD. MOUD = medication for opioid use disorder.

Figure 2.. Monthly receipt of treatments/services, by cohort.

In the 12 mo before and after index opioid overdose, Massachusetts, 2012–2014 (n = 17 568). MMT = methadone maintenance treatment; MOUD = medication for opioid use disorder. * Enrollment in MMT. † Clinical stabilization/step-down or transitional support services.

Figure 3.. Extended Kaplan–Meier cumulative incidence of all-cause mortality (A and B) and opioid-related mortality (C and D), by monthly exposure to MOUD after index overdose.

Massachusetts, 2012–2014 (n = 17 568). MMT = methadone maintenance treatment; MOUD = medication for opioid use disorder. * MOUD exposure extends through the month of discontinuation. † Exposure is limited to months in which treatment was received.