title: Predictors of Opioid-Related Death During Methadone Therapy.
abstract: We aimed to examine pharmacologic, demographic and medical comorbidity risk factors for opioid-related mortality among patients currently receiving methadone for an opioid use disorder. We conducted a population-based, nested case-control study linking healthcare and coroner's records in Ontario, Canada, from January 31, 1994 to December 31, 2010. We included social assistance recipients receiving methadone for an opioid use disorder. Within this group, cases were those who died of opioid-related causes. For each case, we identified up to 5 controls matched on calendar quarter. The primary analysis examined the association between use of psychotropic drugs (benzodiazepines, antidepressants or antipsychotics) and opioid-related mortality. Secondary analyses examined the associations between baseline characteristics, health service utilization, comorbidities and opioid-related mortality. Among 43,545 patients receiving methadone for an opioid use disorder, we identified 175 (0.4%) opioid-related deaths, along with 873 matched controls. Psychotropic drug use was associated with a two fold increased risk of opioid-related death (adjusted odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2 to 3.5). Specifically, benzodiazepines (adjusted OR 1.6; 95% CI 1.1 to 2.5) and antipsychotics (adjusted OR 2.3; 95% CI 1.5 to 3.5) were independently associated with opioid-related death. Other associated factors included chronic lung disease (adjusted OR 1.7; 95% CI 1.2 to 2.6), an alcohol use disorder (adjusted OR 1.9; 95% CI 1.2 to 3.2), mood disorders (adjusted OR 1.8; 95% CI 1.0 to 3.2), and a history of heart disease (adjusted OR 5.3; 95% CI 2.0 to 14.0). Psychotropic drug use is associated with opioid-related death in patients receiving methadone. Mindfulness of these factors may reduce the risk of death among methadone recipients.
authors.affiliation: Public Health and Preventive Medicine, University of Toronto, Ontario, Canada, M5T 3 M7. Electronic address: pamela.leece@mail.utoronto.ca.
authors.forename: Pamela
authors.initials: P
authors.lastname: Leece
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Ontario, Canada, M5G 1 V7. Electronic address: chris.cavacuiti@truenorthmedical.com.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cavacuiti
authors.affiliation: The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5. Electronic address: erin.macdonald@ices.on.ca.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Macdonald
authors.affiliation: The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Ontario, Canada, M5B 1 W8; Institute of Health Policy, Management, and Evaluation, University of Toronto, Ontario, Canada, M5T 3 M6; Leslie Dan Faculty of Pharmacy, University of Toronto, Ontario, Canada, M5S 3 M2. Electronic address: GomesT@smh.ca.
authors.forename: Tara
authors.initials: T
authors.lastname: Gomes
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Ontario, Canada, M5G 1 V7. Electronic address: kahanm@stjoe.on.ca.
authors.forename: Meldon
authors.initials: M
authors.lastname: Kahan
authors.affiliation: St. Joseph's Health Centre, Toronto, Ontario, Canada, M6R 1B6. Electronic address: srivastavaanita@hotmail.com.
authors.forename: Anita
authors.initials: A
authors.lastname: Srivastava
authors.affiliation: Department of Family and Community Medicine, University of Toronto, Ontario, Canada, M5G 1 V7; The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5. Electronic address: lssteele@gmail.com.
authors.forename: Leah
authors.initials: L
authors.lastname: Steele
authors.affiliation: The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5. Electronic address: jin.luo@ices.on.ca.
authors.forename: Jin
authors.initials: J
authors.lastname: Luo
authors.affiliation: The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Ontario, Canada, M5B 1 W8; Institute of Health Policy, Management, and Evaluation, University of Toronto, Ontario, Canada, M5T 3 M6; Applied Health Research Centre, St. Michael's Hospital, Toronto, Ontario, Canada, M5B 1 M8; King Saud University, Riyadh, Saudi Arabia. Electronic address: mamdanim@smh.ca.
authors.forename: Muhammad M
authors.initials: MM
authors.lastname: Mamdani
authors.affiliation: The Institute for Clinical Evaluative Sciences, Ontario, Canada, M4N 3 M5; Institute of Health Policy, Management, and Evaluation, University of Toronto, Ontario, Canada, M5T 3 M6; Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada, M5N 3 M5; The Sunnybrook Research Institute, Toronto, Ontario, M4N 3 M5. Electronic address: david.juurlink@ices.on.ca.
authors.forename: David N
authors.initials: DN
authors.lastname: Juurlink
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000627:therapeutic use*; D008875:Middle Aged; D009864:Ontario / Q000453:epidemiology; D058850:Opiate Substitution Treatment / Q000706:statistics & numerical data*; D009293:Opioid-Related Disorders / Q000401:mortality*; D012307:Risk Factors
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone
keywords: Methadone; Mortality; Opioids; Substance use disorder