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Risk of Overdose with Exposure to Prescription Opioids, Benzodiazepines, and Non-benzodiazepine Sedative-Hypnotics in Adults: a Retrospective Cohort Study

  • Joanne ChoEmail author
  • Michele M. Spence
  • Fang Niu
  • Rita L. Hui
  • Patricia Gray
  • Steven Steinberg
Original Research

Abstract

Background

Concurrent use of benzodiazepines in opioid users has been linked to a higher risk of an emergency room visit or inpatient admission for opioid overdose and death from drug overdose. Further research is needed to confirm the findings and analyze contributing risk factors for opioid overdoses in a large commercially insured population.

Objectives

To estimate the risk of opioid overdose associated with opioid users exposed to various combinations of opioid, benzodiazepine, and non-benzodiazepine sedative-hypnotic therapy. To identify other factors that are associated with increased risk for opioid overdose.

Design

Retrospective cohort study.

Patients

New start adult users of opioids, defined as naïve to opioids for 6 months, in Kaiser Permanente California regions from January 2013 through September 2017.

Main Measures

Inpatient or emergency department admissions due to opioid-related overdose.

Key Results

A total of 2,241,530 patients were included in this study. Patients exposed to opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics at any point during their follow-up were 60% more likely to overdose than those who were only exposed to opioids (p < 0.0001). Those exposed to opioids and benzodiazepines were 20% more likely to have an opioid-related overdose than those exposed to opioids only (p < 0.0001). Significant risk factors for opioid overdose included exposure to all three medication classes, higher opioid dosage strengths, elderly age (age ≥ 65 years), history of previous overdose, and substance use disorder.

Conclusions

Results from this study demonstrate a significant increase in risk of opioid overdose in patients exposed to combinations of sedative-hypnotics with opioids compared to those only taking opioids. Findings from this study provide evidence that opioids should be avoided in combination with benzodiazepines and non-benzodiazepine sedative-hypnotics, used at the lowest dose possible, and used with caution in the elderly, those with previous history of overdose, and those with substance use disorder at baseline.

KEY WORDS

patient centered outcomes research medical safety risk assessment pain 

Notes

Acknowledgments

Contributors: The authors would like to thank Carol Havens, MD, Doris J. Kao, PharmD, BCPS, FCSHP, Jane Takagi, PharmD, FCSHP, FASHP, Maisha Draves, MD, and Sameer Awsare, MD for their support.

Compliance with Ethical Standards

Conflict of Interest

Dr. Steven G. Steinberg is currently employed by Southern California Permanente Medical Group. All remaining authors declare that they do not have a conflict of interest.

Supplementary material

11606_2019_5545_MOESM1_ESM.docx (34 kb)
ESM 1 (DOCX 34 kb)

References

  1. 1.
    Dowell D, Haegerich T, and Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 315.15 (2016): 1624-1645.CrossRefGoogle Scholar
  2. 2.
    Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality.The DAWN Report: Highlights of the 2011 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. February 22, 2013. Available at https://www.samhsa.gov/data/sites/default/files/DAWN127/DAWN127/sr127-DAWN-highlights.htm. Accessed August 27, 2019.
  3. 3.
    Benzodiazepines and Opioids. National Institute on Drug Abuse. https://www.drugabuse.gov/drugs-abuse/opioids/benzodiazepines-opioids. Last updated March 2018. Accessed August 27, 2019.
  4. 4.
    Sun E, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 356 (2017): j760.CrossRefGoogle Scholar
  5. 5.
    Park T, Saitz R, Ganoczy D, et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 350 (2015): h2698.CrossRefGoogle Scholar
  6. 6.
    Garg R, Fulton-Kehoe D, and Franklin G. Patterns of Opioid Use and Risk of Opioid Overdose Death Among Medicaid Patients. Medical Care 55.7 (2017): 661-668.CrossRefGoogle Scholar
  7. 7.
    Kaiser Permanente. Fast Facts About Kaiser Permanente. 2018. Available at https://about.kaiserpermanente.org/who-we-are/fast-facts. Accessed August 27, 2019.
  8. 8.
    Losby J, Hyatt J, Kanter M, et al. Safer and more appropriate opioid prescribing: a large healthcare system’s comprehensive approach. J Eval in Clin Practice (2017).Google Scholar
  9. 9.
    Prescription Drug Monitoring Program Training and Technical Assistance Center at Brandeis University. Technical assistance guide No. 01-13: Calculating daily morphine milligram equivalents. 2013. Available at: http://www.pdmpassist.org/pdf/BJA_performance_measure_aid_MME_conversion.pdf. Accessed August 27, 2019.
  10. 10.
    Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005; 43(11):1130-1139CrossRefGoogle Scholar
  11. 11.
    Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305(13):1315-1321.CrossRefGoogle Scholar
  12. 12.
    Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010; 152(2):85-92.CrossRefGoogle Scholar
  13. 13.
    Gomes T, Mamdani MM, Dhalla IA, et al. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171:686-691.PubMedGoogle Scholar
  14. 14.
    Nadpara PA, Joyce AR, Murrelle EL, et al. Risk Factors for Serious Prescription Opioid-Induced Respiratory Depression or Overdose: Comparison of Commercially Insured and Veterans Health Affairs Populations. Pain Medicine. 2017;19(1):79-96.CrossRefGoogle Scholar
  15. 15.
    Henry J Kaiser Family Foundation. Opioid Overdose Deaths by Race/Ethnicity. Available at https://www.kff.org/other/state-indicator/opioid-overdose-deaths-by-raceethnicity/. Accessed August 27, 2019.

Copyright information

© Society of General Internal Medicine 2020

Authors and Affiliations

  • Joanne Cho
    • 1
    Email author
  • Michele M. Spence
    • 2
  • Fang Niu
    • 2
  • Rita L. Hui
    • 2
    • 3
  • Patricia Gray
    • 4
  • Steven Steinberg
    • 5
  1. 1.Pharmacy Services Kaiser PermanenteBakersfieldUSA
  2. 2.Pharmacy Outcomes Research GroupDowneyUSA
  3. 3.Pharmacy Outcomes Research GroupOaklandUSA
  4. 4.Pharmacy ServicesKaiser PermanenteRiversideUSA
  5. 5.Southern California Permanente Medical GroupPasadenaUSA

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