Journal of General Internal Medicine

, Volume 33, Issue 9, pp 1512–1519 | Cite as

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

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



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


To examine the association between PIP and adverse events.


Cohort study.


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).


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.


potentially inappropriate prescribing overdose opioids mortality 



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


Conflict of Interest

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


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, Dataset: those interested in using the data may contact Dana Bernson (email, 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)


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Copyright information

© Society of General Internal Medicine 2018

Authors and Affiliations

  • Adam J. Rose
    • 1
    • 2
    Email author
  • 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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