Potentially Inappropriate Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011–2015

  • Adam J. Rose
  • Dana Bernson
  • Kenneth Kwan Ho Chui
  • Thomas Land
  • Alexander Y. Walley
  • Marc R. LaRochelle
  • Bradley D. Stein
  • Thomas J. Stopka
Original Research

Abstract

Background

Potentially inappropriate prescribing (PIP) may contribute to opioid overdose.

Objective

To examine the association between PIP and adverse events.

Design

Cohort study.

Participants

Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015.

Main Measures

We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates.

Key Results

All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02–2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59–1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85–4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14–2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01–2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p < 0.001).

Conclusions

PIP was associated with higher hazard for all-cause mortality, fatal overdose, and non-fatal overdose. Our study implies the possibility of creating a risk score incorporating multiple PIP subtypes, which could be displayed to prescribers in real time.

KEY WORDS

potentially inappropriate prescribing overdose opioids mortality 

Notes

Funding

This study was funded by the GE Foundation (PI: Stopka). The funder had no role in the design, conduct, or reporting of the study.

Compliance with Ethical Standards

Prior Presentations

None

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Disclaimer

The opinions expressed in this manuscript are those of the authors and do not represent the official views or policies of the Massachusetts Department of Public Health or the Commonwealth of Massachusetts.

Responsible Research Statement

Study protocol and statistical code: available from Dr. Rose (email, arose@rand.org). Dataset: those interested in using the data may contact Dana Bernson (email, dana.bernson@state.ma.us). All interested parties are encouraged to apply; however, permission to use the data will be prioritized in accordance with current Massachusetts Department of Public Health priorities.

Supplementary material

11606_2018_4532_MOESM1_ESM.docx (154 kb)
ESM 1 (DOCX 154 kb)

References

  1. 1.
    Rudd RA, Seth P, David F, Scholl L. Increases in drug and opioid-involved overdose deaths—United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65:1445–52.CrossRefPubMedGoogle Scholar
  2. 2.
    Schuchat A, Houry D, Guy GP. New data on opioid use and prescribing in the United States. JAMA. 2017;318:425–426.CrossRefPubMedGoogle Scholar
  3. 3.
    Jones CM, Paulozzi LJ, Mack KA. Sources of prescription opioid pain relievers by frequency of past-year nonmedical use United States, 2008-2011. JAMA Intern Med. 2014;174:802–3.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu Y, Logan JE, Paulozzi LJ, Zhang K, Jones CM. Potential misuse and inappropriate prescription practices involving opioid analgesics. Am J Manag Care. 2013;19:648–665.PubMedGoogle Scholar
  5. 5.
    Paulozzi LJ, Strickler GK, Kreiner PW, Koris CM. Controlled substance prescribing patterns—prescription behavior surveillance system, eight states, 2013. MMWR Surveill Summ. 2015;64(SS09):1–14.CrossRefPubMedGoogle Scholar
  6. 6.
    Gellad WF, Zhao X, Thorpe CT, et al. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among veterans dually enrolled in Department of Veterans Affairs and Medicare Part D. Subst Abus. 2017;38:22–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Gwira Baumblatt JA, Wiedeman C, et al. High-risk use by patients prescribed opioids for pain and its role in overdose deaths. JAMA Intern Med. 2014;174:796–801.CrossRefPubMedGoogle Scholar
  8. 8.
    Bohnert AS, Logan JE, Ganoczy D, Dowell D. A detailed exploration into the association of prescribed opioid dosage and overdose deaths among patients with chronic pain. Med Care. 2016;54:435–41.CrossRefPubMedGoogle Scholar
  9. 9.
    Bohnert AS, Valenstein M, Bair MJ, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315–21.CrossRefPubMedGoogle Scholar
  10. 10.
    Dunn KM, Saunders KW, Rutter CM, et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010;152:85–92.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zedler B, Xie L, Wang L, et al. Risk factors for serious prescription opioid-related toxicity or overdose among Veterans Health Administration patients. Pain Med. 2014;15:1911–29.CrossRefPubMedGoogle Scholar
  12. 12.
    Gomes T, Mamdani MM, Dhalla IA, Paterson JM, Juurlink DN. Opioid dose and drug-related mortality in patients with nonmalignant pain. Arch Intern Med. 2011;171:686–91.PubMedGoogle Scholar
  13. 13.
    Garg RK, Fulton-Kehoe D, Franklin GM. Patterns of opioid use and risk of opioid overdose death among medicaid patients. Med Care. 2017;55:661–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Cochran G, Gordon AJ, Lo-Ciganic WH, et al. An examination of claims-based predictors of overdose from a large medicaid program. Med Care. 2017;55:291–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med. 2016;17:85–98.PubMedGoogle Scholar
  16. 16.
    Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hall AJ, Logan JE, Toblin RL, et al. Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA. 2008;300:2613–20.CrossRefPubMedGoogle Scholar
  18. 18.
    Yang Z, Wilsey B, Bohm M, et al. Defining risk of prescription opioid overdose: pharmacy shopping and overlapping prescriptions among long-term opioid users in medicaid. J Pain. 2015;16:445–53.CrossRefPubMedGoogle Scholar
  19. 19.
    Commonwealth of Massachusetts: Chapter 55 Website. Accessed at http://www.mass.gov/eohhs/gov/departments/dph/stop-addiction/chapter-55-overdose-assessment.html on May 22, 2018.
  20. 20.
    Chapter 55: An Act Requiring Certain Reports for Opiate Overdoses – Initial Report. Accessed at http://www.mass.gov/eohhs/docs/dph/stop-addiction/dph-legislative-report-chapter-55-opioid-overdose-study-9-15-2016.pdf on May 22, 2018.
  21. 21.
    Report to the Massachuetts Legislature. “An Assessment of Fatal and Nonfatal Opioid Overdoses in Massachusetts (2011–2015).” Available at: https://www.mass.gov/files/documents/2017/08/31/legislative-report-chapter-55-aug-2017.pdf. Accessed May 22, 2018.
  22. 22.
    Ruhm CJ. Geographic variation in opioid and heroin involved drug poisioning mortality rates. Am J Prev Med. 2017;53:745–53.CrossRefPubMedGoogle Scholar
  23. 23.
    Rockett IR, Hobbs GR, Wu D, et al. Variable classification of drug-intoxication suicides across US states: a partial artifact of forensics? PLoS One. 2015;10:e0135296.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    United States Census Bureau. American FactFinder. Accessed at http://factfinder.census.gov/ on May 22, 2018.
  25. 25.
    Krieger N, Chen JT, Waterman PD, Rehkopf DH, Subramanian SV. Painting a truer picture of US socioeconomic and racial/ethnic health inequalities: the Public Health Disparities Geocoding Project. Am J Public Health. 2005;95:312–23.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    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;43:1130–9.CrossRefPubMedGoogle Scholar
  27. 27.
    VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the E-value. Ann Intern Med. 2017;167:268–74.CrossRefPubMedGoogle Scholar
  28. 28.
    Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315:1624–45.PubMedGoogle Scholar
  29. 29.
    Massachusetts Medical Society. Smart and safe: information about opioid medications for patients, prescribers, and policymakers. Accessed at http://www.massmed.org/smartandsafe/ on May 22, 2018.
  30. 30.
    Guy GP, Zhang K, Bohm MK, et al. Vital signs: changes in opioid prescribing in the United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66:697–704.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    US Food and Drug Administration. FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. Available at: https://www.fda.gov/Drugs/DrugSafety/ucm518473.htm. Accessed May 22, 2018.
  32. 32.
    Katz N, Panas L, Kim M, et al. Usefulness of prescription monitoring programs for surveillance—analysis of Schedule II opioid prescription data in Massachusetts, 1996-2006. Pharmacoepidemiol Drug Saf. 2010;19:115–23.CrossRefPubMedGoogle Scholar
  33. 33.
    Pardo B. Do more robust prescription drug monitoring programs reduce prescription opioid overdose? Addiction. 2016;112:1773–83.CrossRefGoogle Scholar
  34. 34.
    Miller M, Barber CW, Leatherman S, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA Intern Med. 2015;175:608–15.CrossRefPubMedGoogle Scholar
  35. 35.
    Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Prescription of long-acting opioids and mortality in patients with chronic noncancer pain. JAMA. 2016;315:2415–23.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Society of General Internal Medicine 2018

Authors and Affiliations

  • Adam J. Rose
    • 1
    • 2
  • Dana Bernson
    • 3
  • Kenneth Kwan Ho Chui
    • 4
  • Thomas Land
    • 3
  • Alexander Y. Walley
    • 2
    • 3
  • Marc R. LaRochelle
    • 2
  • Bradley D. Stein
    • 5
    • 6
  • Thomas J. Stopka
    • 4
    • 7
  1. 1.RAND CorporationBostonUSA
  2. 2.Section of General Internal MedicineBoston University School of Medicine and Boston Medical CenterBostonUSA
  3. 3.Massachusetts Department of Public HealthBostonUSA
  4. 4.Tufts University School of MedicineBostonUSA
  5. 5.RAND CorporationPittsburghUSA
  6. 6.University of Pittsburgh School of MedicinePittsburghUSA
  7. 7.Tufts Clinical and Translational Sciences InstituteBostonUSA

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