Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control Study
Authors: Tara Gomes, Simon Greaves, Wim van den Brink, Tony Antoniou, Muhammad M. Mamdani, J. Michael Paterson, Diana Martins, David N. Juurlink
Journal: Annals of Internal Medicine (2018)

Letters20 November 2018Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control StudyTara Gomes, MHSc, PhD, Simon Greaves, MSc, Wim van den Brink, MD, PhD, Tony Antoniou, PharmD, PhD, Muhammad M. Mamdani, PharmD, MA, MPH, J. Michael Paterson, MSc, Diana Martins, MSc, and David N. Juurlink, MD, PhDTara Gomes, MHSc, PhDLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.), Simon Greaves, MScInstitute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (S.G.), Wim van den Brink, MD, PhDAcademic Medical Center University of Amsterdam, Amsterdam, the Netherlands (W.V.), Tony Antoniou, PharmD, PhDLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.), Muhammad M. Mamdani, PharmD, MA, MPHLi Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.), J. Michael Paterson, MScInstitute for Clinical Evaluative Sciences and University of Toronto, Toronto, Ontario, Canada (J.M.P.), Diana Martins, MScLi Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (D.M.), and David N. Juurlink, MD, PhDInstitute for Clinical Evaluative Sciences, Sunnybrook Research Institute, and University of Toronto, Toronto, Ontario, Canada (D.N.J.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-1136 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail 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 population-based, nested case–control study of Ontario residents eligible for public drug coverage who received ...References1. Toth C. Drug safety evaluation of pregabalin. Expert Opin Drug Saf. 2012;11:487-502. [PMID: 22468635] doi:10.1517/14740338.2012.677026 CrossrefMedlineGoogle Scholar2. Goodman CW, Brett AS. Gabapentin and pregabalin for pain—is increased prescribing a cause for concern? N Engl J Med. 2017;377:411-4. [PMID: 28767350] doi:10.1056/NEJMp1704633 CrossrefMedlineGoogle Scholar3. Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49:661-9. [PMID: 20818832] doi:10.2165/11536200-000000000-00000 CrossrefMedlineGoogle Scholar4. Gomes T, Juurlink DN, Antoniou T, Mamdani MM, Paterson JM, van den Brink W. Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study. PLoS Med. 2017;14:e1002396. [PMID: 28972983] doi:10.1371/journal.pmed.1002396 CrossrefMedlineGoogle Scholar5. Kwok H, Khuu W, Fernandes K, Martins D, Tadrous M, Singh S, et al. Impact of unrestricted access to pregabalin on the use of opioids and other CNS-active medications: a cross-sectional time series analysis. Pain Med. 2017;18:1019-26. [PMID: 28340102] doi:10.1093/pm/pnw351 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Li Ka Shing Knowledge Institute of St. Michael's Hospital, Institute for Clinical Evaluative Sciences, and University of Toronto, Toronto, Ontario, Canada (T.G., T.A., M.M.M.)Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (S.G.)Academic Medical Center University of Amsterdam, Amsterdam, the Netherlands (W.V.)Institute for Clinical Evaluative Sciences and University of Toronto, Toronto, Ontario, Canada (J.M.P.)Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada (D.M.)Institute for Clinical Evaluative Sciences, Sunnybrook Research Institute, and University of Toronto, Toronto, Ontario, Canada (D.N.J.)See also: Editorial comment (page 727).Note: The funding source had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Mr. Greaves had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Disclaimer: The opinions, results, and conclusions reported here are those of the authors and are independent from those of the funding sources. No endorsement by the Institute for Clinical Evaluative Sciences or the Ontario Ministry of Health and Long-Term Care is intended or should be inferred. The analyses, conclusions, opinions, and statements expressed here are those of the authors and not necessarily those of the Canadian Institute for Health Information.Acknowledgment: The authors thank Brogan Ottawa for use of their drug product and therapeutic class database and the Canadian Institute for Health Information, which compiled and provided data and information on which parts of this report are based.Grant Support: From the Ontario Ministry of Health and Long-Term Care (06673).Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-1136.Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Gomes (e-mail, [email protected]ca). Data set: Available to those who meet prespecified criteria for confidential access at www.ices.on.ca/DAS.This article was published at Annals.org on 21 August 2018. 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Throckmorton, MD and Janet Woodcock, MDPregabalin increases risk of opioid-related death 20 November 2018Volume 169, Issue 10Page: 732-734KeywordsDisclosureDrug regulationDrugsHealth careHealth information technologyInformation storage and retrievalLong-term careMortalityNSAIDsOpioids ePublished: 21 August 2018 Issue Published: 20 November 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...