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

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The United States is in the midst of a crisis of opioid-related harms (1). Some efforts to address this crisis focus on expanding access to effective treatment of opioid use disorders (OUDs) (2). Prior nonfatal opioid overdose is a known risk factor for subsequent nonfatal and fatal overdoses (3–7), and engaging persons in treatment who survive an overdose may be effective in limiting subsequent fatalities. However, data on the association between treatment of OUD and mortality after a nonfatal overdose are limited to a single retrospective cohort study that analyzed enrollment in methadone maintenance treatment (MMT) at a single time point and found no association (3).
The 3 medications for OUD (MOUD) approved by the U.S. Food and Drug Administration are methadone, buprenorphine, and naltrexone. Randomized controlled trials of these medications have shown consistent benefits across many outcomes, including increased treatment retention and suppression of illicit opioid use (8–10). A recent systematic review and meta-analysis of 19 observational cohort studies identified substantial reductions in all-cause and overdose mortality for methadone and buprenorphine (11). However, the mortality benefit in this analysis was limited to time actively retained in treatment, and the 4-week period after discontinuation was associated with an especially high risk for death. The few studies that examined mortality among patients receiving naltrexone show an unclear effect (12–15).
Massachusetts has been particularly affected by the opioid crisis: Opioid overdose deaths more than tripled between 2010 and 2016 (16). Through Chapter 55 of the Acts of 2015, the state legislature permitted individual-level linkage of data from 16 Massachusetts government agencies to gain a deeper understanding of the circumstances that influence fatal and nonfatal opioid overdoses (17). For this analysis, we identified a cohort of persons in the Chapter 55 data set who survived an opioid overdose and described any episodes of treatment with MOUD before and after that overdose. Specifically, we sought to determine whether treatment with MOUD, including receipt of MMT, buprenorphine, or naltrexone, was associated with reduced risk for all-cause and opioid-related mortality.

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