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Research Article: Impact of opioid agonist therapies on non-fatal and fatal overdose: treatment patterns among individuals with opioid use disorder in Ontario, Canada

Date Published: 2026-09-29

Abstract:
Although opioid agonist therapies (OAT) including buprenorphine extended-release (BUP-XR), transmucosal buprenorphine (TM-BUP), methadone and slow-release oral morphine (SROM) are effective and established medications for opioid use disorder (MOUD) available in Canada, differences in opioid-related overdose (OD) risk reduction across OAT types and patterns of treatment use are not well characterized. To assess the impact of OAT on opioid-related non-fatal and fatal OD among individuals with OUD in Ontario, Canada, and to examine patterns of OAT use. A retrospective, population-based, nested case-control study was conducted using ICES administrative health data. Adults with opioid use disorder (OUD) who were administered ?1 OAT from January 2022 through June 2024 were included. Cases with opioid-related non-fatal or fatal OD were matched 1:10 to controls on age, sex, and follow-up duration. Adjusted odds ratios were estimated using weighted exact conditional logistic regression. Among 45,243 individuals with OUD who started OAT, 4,109 (9.1%) experienced a non-fatal OD and 770 (1.7%) had a fatal OD. Fatal OD cases were most commonly aged 35–49?years; non-fatal cases were most prevalent among those aged 18–34?years. Most OD cases were male and resided in urban areas. Substance use disorders other than OUD and anxiety disorders were more prevalent among OD cases than controls. Of non-fatal and fatal OD cases, 75.9% and 84.9% were not covered by an OAT for at least 80% of the time between cohort entry and index OD event, respectively. Of all OATs, BUP-XR had the lowest proportion of patients with non-fatal and fatal OD compared to no treatment. Both BUP-XR and TM-BUP were associated with significantly lower odds of non-fatal and fatal OD compared to no OAT, while methadone and SROM did not show similar improvements. OAT type and treatment continuity were associated with different OD risk reductions. Supporting sustained OAT engagement and expanding access to buprenorphine, including BUP-XR, may reduce non-fatal and fatal OD risk among individuals with OUD. Limitations include potential misclassification in administrative data, incomplete or inaccurate capture of opioid-related OD events and OAT use, and absence of a direct measure of OAT adherence.

Introduction:
Although opioid agonist therapies (OAT) including buprenorphine extended-release (BUP-XR), transmucosal buprenorphine (TM-BUP), methadone and slow-release oral morphine (SROM) are effective and established medications for opioid use disorder (MOUD) available in Canada, differences in opioid-related overdose (OD) risk reduction across OAT types and patterns of treatment use are not well characterized.

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