Pregabalin and the Risk for Opioid-Related Death: A Nested Case–Control Study
Year: 2018
Type: article
Study design: Observational Study
Abstract: 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. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCombined Gabapentinoid and Opioid Use: The Consequences of Shifting Prescribing Trends Douglas C. Throckmorton and Janet Woodcock Metrics Cited byPharmacist, prescriber, and drug policy expert opinions on gabapentinoid misuseThe use of gabapentinoids and opioids and risk of developing opioid-induced respiratory depression among older breast cancer survivors with neuropathic painTrends in gabapentinoid prescribing in UK primary care using the Clinical Practice Research Datalink: an observational studyUse of Opioids for Adults With Pain From Cancer or Cancer Treatment: ASCO GuidelineA Randomized Trial Of Letters To Encourage Prescription Monitoring Program Use And Safe Opioid PrescribingConcurrent prescribing of opioids with other sedating medications after cancer diagnosis: a population-level analysisEvaluation of concurrent benzodiazepine and opioid prescribing patterns with a focus on acute muscle spasms indication at hospital dischargePolypharmacy Patterns in Multimorbid Older People with Cardiovascular Disease: Longitudinal StudyCDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022Identifying Clinically Relevant Drug–Drug Interactions With Methadone and Buprenorphine: A Translational Approach to Signal DetectionRisk of major adverse events associated with gabapentinoid and opioid combination therapy: A systematic review and meta-analysisCorrelates of Opioid Use Among Ontario Long-Term Care Residents and Variation by Pain Frequency and Intensity: A Cross-sectional AnalysisAnalgesic Efficacy of Gabapentin and Pregabalin in Patients Undergoing Laparoscopic Bariatric Surgeries: a Systematic Review and Meta-analysisOutpatient Opioid and Naloxone Prescribing Practices at an Academic Medical Center during the COVID-19 PandemicTrends in Prescriptions for Non-opioid Pain Medications Among U.S. Adults With Moderate or Severe Pain, 2014-2018Patient empowerment brochures to increase gabapentinoid deprescribing: protocol for the prospective, controlled before-and-after GABA-WHY trialOral Morphine as an Alternative Substitution Treatment for Opioid Use Disorder, a Rare but Non-risk-free UseNon-opioid analgesics and post-operative pain following transoral robotic surgery for oropharyngeal cancerUse of pharmacological and nonpharmacological treatments for chronic noncancer pain among people using opioids: a longitudinal cohort studyToxicological Relevance of Pregabalin in Heroin Users: A Two-Year Postmortem Population StudyInterventions for Depressive Symptoms in People Living with Chronic Pain: A Systematic Review of Meta-AnalysesThe impact of regulatory restrictions on pregabalin use in Saudi Arabia: An interrupted time series analysisConcurrent Use of Prescription Opioids and Gabapentinoids in Older AdultsKnowledge transfer to patients experiencing pain and poor sleep and sleep disorderOpioid use disorder in anaesthesia and intensive care: Prevention, diagnosis and managementConcurrent use of prescription gabapentinoids with opioids and risk for fall-related injury among older US Medicare beneficiaries with chronic noncancer pain: A population-based cohort studyOpioids for chronic pain management in patients with dialysis-dependent kidney failureRisk Prescriptions of Strong Opioids in the Treatment of Chronic Non-Cancer Pain by Primary Care Physicians in Catalonia: Opicat Padris ProjectCentral nervous system polytherapy among veterans with posttraumatic stress disorder: changes across a decadeAn update on postoperative respiratory depressionAssociation of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort studyAssociation between opioid-related deaths and prescribed opioid dose and psychotropic medicines in England: a case-crossover studyThe gabapentinoid drugs and their abuse potentialCoprescription of Opioids With Other Medications and Risk of Opioid OverdoseInvestigating the prescribing trajectory and geographical drug utilisation patterns of gabapentinoids in primary care in England: An ecological studyThe iatrogenic opioid crisis: An example of 'institutional corruption of pharmaceuticals'?Pediatric Palliative Care Pharmacy Pearls—A Focus on Pain and SedationOpioids and Gabapentinoids Utilisation and Their Related-Mortality Trends in the United Kingdom Primary Care Setting, 2010–2019: A Cross-National, Population-Based Comparison StudyLong-term Patterns of Self-reported Opioid Use, VACS Index, and Mortality Among People with HIV Engaged in CareOpioid prescribing and health outcomes in opioid-naive patients: Analysis of a statewide health information exchangeGabapentinoid Pharmacology in the Context of Emerging Misuse LiabilityGabapentinoid misuse, abuse and non-prescribed obtainment in a United States general population sampleCharacterization of hospitalized patients who received naloxone while receiving opioids with or without gabapentinoidsLetter to the Editor: Comment on "Gabapentinoid Benefit and Risk Stratification: Mechanisms Over Myth"Opioid prescribing and risk of drug-opioid interactions in older discharged patients with polypharmacy in AustraliaAuthors' Reply to Bonnet et al. "Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update"Impact of pregabalin co-use in patients presenting with acute heroin toxicity to the European Drug Emergencies Network Plus projectDual‐trajectories of opioid and gabapentinoid use and risk of subsequent drug overdose among Medicare beneficiaries in the United States: a retrospective cohort studyCohort profile: development and characteristics of a retrospective cohort of individuals dispensed prescription opioids for non-cancer pain in British Columbia, CanadaInitial opioid prescription patterns and the risk of ongoing use and adverse outcomesPrevalence of and Factors Associated with Gabapentinoid Use and Misuse Among Texas Medicaid RecipientsA cross sectional study of psychotropic medicine use in Australia in 2018: A focus on polypharmacyAssociation Between Dual Trajectories of Opioid and Gabapentinoid Use and Healthcare Expenditures Among US Medicare BeneficiariesAnalgesic opioid use disorders in patients with chronic non-cancer pain: A holistic approach for tailored managementPregabalin for neuropathic pain in primary care settings: recommendations for dosing and titrationManagement of Musculoskeletal PainAbuse and Misuse of Pregabalin and Gabapentin: A Systematic Review UpdateManaging the misuse potential and risk of psychological harm from gabapentinoids in primary care in New ZealandFrequency of Concomitant Use of Gabapentinoids and Opioids among Patients with Cancer-Related Pain at an Outpatient Palliative Care ClinicThe Use and Concurrent Use of Side Effect Controlling Medications Among Women on Aromatase InhibitorsPregabalin prescribing patterns in Australian general practice, 2012–2018: a cross-sectional studyOpioid Prescribing with Take-Home Naloxone: Rationale and RecommendationsObtention illégale de prégabaline comme proxy de l'usage non médical : analyse nationale multisource du Réseau Français d'AddictovigilanceSahaj Samadhi Meditation versus a Health Enhancement Program for depression in chronic pain: protocol for a randomized controlled trial and implementation evaluationEntropy: A Promising EEG Biomarker Dichotomizing Subjects With Opioid Use Disorder and Healthy ControlsPharmacological treatment of central neuropathic pain: consensus of the Brazilian Academy of NeurologyEffects of Acetaminophen, NSAIDs, Gabapentinoids, and Their Combinations on Postoperative Pulmonary Complications After Total Hip or Knee ArthroplastyPregabalin: a better neuropathic pain treatment in rodents than in humansThe Lancet Series call to action to reduce low value care for low back pain: an updatePatterns of pregabalin initiation and discontinuation after its subsidy in AustraliaPotentially inappropriate prescribing in older adults with advanced chronic kidney diseaseManage acute pain in opioid-tolerant patients with simple analgesics and adjuvants, along with increased doses of opioids if necessaryPatterns and correlates of prescribed and non‐prescribed pregabalin use among a sample of people who inject drugs in AustraliaManaging Opioids, Including Misuse and Addiction, in Patients With Serious Illness in Ambulatory Palliative Care: A Qualitative StudyThoughts on the 2019 American Academy of Sleep Medicine position statement on chronic opioid therapy and sleepPregabalin and injury: A nested case‐control and case‐crossover studyUse of promethazine, gabapentin and clonidine in combination with opioids or opioid agonist therapies among individuals attending a syringe service programUnderstanding Buprenorphine for Use in Chronic Pain: Expert OpinionPreliminary Evidence of Pregabalin Misuse among Prescription and/or Illicit Opioid (Mis)usersPostoperative opioid‐prescribing practices in otolaryngology: A multiphasic studyOpioid Alternative Medication and Clinical DilemmasManagement of Opioid-Tolerant Patients with Acute Pain: Approaching the ChallengesCharacteristics Associated With U.S. Outpatient Opioid Analgesic Prescribing and Gabapentinoid Co-PrescribingReceipt of Substance Use Counseling Among Ambulatory Patients Prescribed Opioids in the United StatesTrends, Patient and Prescriber Characteristics in Gabapentinoid Use in a Sample of United States Ambulatory Care Visits from 2003 to 2016Perioperative Acute Care of Older Patients Living with FrailtyPrescription of benzodiazepines, z-drugs, and gabapentinoids and mortality risk in people receiving opioid agonist treatment: Observational study based on the UK Clinical Practice Research Datalink and Office for National Statistics death recordsTrends in prior receipt of prescription opioid or adjuvant analgesics among patients with incident opioid use disorder or opioid-related overdose from 2006 to 2016Retrospective Cohort Study of the Prevalence of Off‐label Gabapentinoid Prescriptions in Hospitalized Medical PatientsOften Off‐label: Questionable Gabapentinoid Use Noted at Hospital Admission Warrants DeprescribingMisuse and Mortality Related to Gabapentin and Pregabalin are Being Under-Estimated: A Two-Year Post-Mortem Population StudyOpioids Aware: a general practice audit of high-dose opioid prescribing NHS England Midlands and EastPrevention of Opioid OverdoseMedicare Formulary Coverage and Restrictions for Opioid Potentiators from 2013 to 2017Enduring legacy of opioid-related harmPotentially Unsafe Chronic Medication Use Among Older Adult Chronic Opioid UsersPregabalin misuse‐related ambulance attendances in Victoria, 2012–2017: characteristics of patients and attendancesPregabalin misuse: the next wave of prescription medication problemsReferencesAnti-epileptic medicationsConsiderations in 2017–2018 for the Use of Opioids in Non-terminal PainCombined Gabapentinoid and Opioid Use: The Consequences of Shifting Prescribing TrendsDouglas C. 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 ...
Source: Annals of Internal Medicine
DOI: 10.7326/m18-1136
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2888071069
