Concurrent prescriptions for opioids and benzodiazepines and risk of opioid overdose: protocol for a retrospective cohort study using linked administrative data

Abstract

Introduction: Opioid overdoses have increased substantially over the last 20 years, with over 400 000 deaths in North America. While opioid prescribing has been a target of research, benzodiazepine and opioid co-intoxication has emerged as a potential risk factor. Our aim was to assess the risk of opioid overdose associated with concurrent use of opioids and benzodiazepines relative to opioids alone.

Methods and analysis: A retrospective cohort study will be conducted using medical claims data from adult residents of Montréal, Canada. We will create a cohort of new users of opioids (ie, no opioid dispensations in prior year) in 2000-2014 from people with at least 2 years of continuous health insurance. Those with any diagnosis or hospitalisation for cancer or palliative care in the 2 years before their first opioid dispensation will be excluded. On each person-day of follow-up, exposure status will be classified into one of four mutually exclusive categories: (1) opioid-only, (2) benzodiazepine-only, (3) both opioid and benzodiazepine (concurrent use) or (4) neither. Opioid overdose will be measured using diagnostic codes documented in the hospital discharge abstract database, physician billing claims from emergency department visits and death records. Using a marginal structural Cox proportional hazards model, we will compare the hazard of overdose during intervals of concurrent opioid and benzodiazepine use to intervals of opioid use alone, adjusted for sociodemographics, medical and psychiatric comorbidities, and substance use disorders.

Ethics and dissemination: This study is approved by the McGill Faculty of Medicine Institutional Review Board and the Commission d'access à l'information (Québec privacy commission). Results will be relevant to clinicians, policymakers and other researchers interested in co-prescribing practices of opioids and benzodiazepines. Study findings will be disseminated at relevant conferences and published in biomedical and epidemiological peer-reviewed journals.

Keywords: adverse events; epidemiology; public health.

Figure 1

The purpose of this figure is to show how exposure will be assigned using three fictitious patients to illustrate. Patient (A) enters the cohort with no opioid and benzodiazepine use, as shown by the section in white. Then, they receive their opioid prescription (blue), which ends right before they begin their benzodiazepine prescription (orange). During their period of benzodiazepine use, however, they receive another opioid prescription that overlaps this benzodiazepine period (red). Since they were using both drugs the day before an overdose, this patient’s event would be exposed to concurrent drug use. Patient (B) enters our study already using benzodiazepines (orange), then stops for a period of time (white) before receiving a short prescription for opioids (blue) and then continues their period of non-use (white). Patient (C) enters the study using neither drug (white), but then begins a long duration of opioid-only use (blue) before experiencing the event. Since they were exposed to opioids only in the day before overdose, their event would be considered unexposed to concurrent drug use.