Association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy: A retrospective cohort study from British Columbia, Canada.

Aims: We measured the association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy (OAT) for opioid use disorder.

Design: Retrospective cohort study using the British Columbia Provincial Overdose Cohort, a linked administrative database.

Setting: We used data from British Columbia, Canada, from January 2015 through February 2020.

Participants: In total, 9395 individuals contributed 18 273 person-years of follow-up while dispensed OAT.

Measurements: We examined the association between stimulant prescription (primary exposure) and fatal or non-fatal overdose (primary outcome, allowing for recurrent events) after adjusting for potential confounders including sociodemographic characteristics and substance use patterns. As a secondary analysis, we evaluated type of OAT (full agonists involving methadone or slow-release oral morphine versus partial agonist involving buprenorphine/naloxone alone) as a potential effect modifier.

Findings: There were 1746 overdose events; 37 (2.1%) were fatal. Overall, there was no increased risk of overdose among individuals dispensed a stimulant medication while on OAT [adjusted Cox regression hazard ratio (AHR) = 1.13, 95% confidence interval (95% CI) = 0.86-1.49, P = 0.39]. When analyzed by type of OAT medication, for individuals on buprenorphine, dispensation of a stimulant medication was associated with a reduced risk of overdose (AHR = 0.47, 95% CI = 0.23-0.96, P = 0.037) while, for individuals on full agonist OAT, dispensation of a stimulant medication was associated with an increased risk of overdose (AHR = 1.51, 95% CI = 1.09-2.07, P = 0.012).

Conclusions: There does not appear to be an overall increased risk of overdose for individuals co-prescribed a stimulant medication with opioid agonist therapy (OAT). There appears to be a reduced risk of overdose for individuals dispensed buprenorphine with a stimulant medication compared with those dispensed buprenorphine alone, and an increased risk of overdose for individuals dispensed full agonist OAT (methadone or slow-release oral morphine) with a stimulant medication compared with those dispensed full agonist OAT alone.