Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control Study

Background: Pregabalin is an anticonvulsant that is increasingly being prescribed as an adjunct for chronic pain (1, 2).However, it can be sedating and may augment central nervous system (CNS) depression in patients also receiving opioids (3).Because recent evidence shows that concomitant opioid and gabapentin use is associated with opioid-related mortality (4), understanding whether similar risks exist when pregabalin is coprescribed with opioids is essential.Objective: To examine the risk for opioid-related death among persons coprescribed pregabalin and opioids.Methods and Findings: We conducted a populationbased, nested case-control study of Ontario residents eligible for public drug coverage who received prescription opioids between 1 August 1997 and 31 December 2016.The study was approved by the Research Ethics Board of Sunnybrook Health Sciences Centre.The methods, data sources, and statistical analyses are consistent with those reported in our previous study examining the concomitant use of opioids and gabapentin (4).Any differences are described.We identified a cohort of persons aged 15 to 105 years who received publicly funded opioid prescriptions over the study period.Case patients were defined as those who died of an opioid-related cause, excluding deaths determined to be suicide or homicide; the index date was the date of the opioid-related death.Each case patient was matched to up to 4 control participants on the basis of age (within 3 years), sex, index year (within 1 year), history of chronic kidney disease (within the previous 5 years), and Charlson comorbidity index score (within 0.2 SDs).In a sensitivity analysis, we also Table.Baseline Characteristics of Persons Who Died of Opioid Overdose (Case Patients) and Matched Control Participants* Characteristic