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

AimsWe measured the association between prescribed stimulant medications and overdose among individuals receiving opioid agonist therapy (OAT) for opioid use disorder.DesignRetrospective cohort study using the British Columbia Provincial Overdose Cohort, a linked administrative database.SettingWe used data from British Columbia, Canada, from January 2015 through February 2020.ParticipantsIn total, 9395 individuals contributed 18 273 person-years of follow-up while dispensed OAT.MeasurementsWe 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.FindingsThere 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).ConclusionsThere 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.