First Opioid Prescription and Subsequent High-Risk Opioid Use: a National Study of Privately Insured and Medicare Advantage Adults

  • Yongkang Zhang
  • Phyllis Johnson
  • Philip J. Jeng
  • M. Carrington Reid
  • Lisa R. Witkin
  • Bruce R. Schackman
  • Jessica S. Ancker
  • Yuhua Bao
Original Research



National guidelines make recommendations regarding the initial opioid prescriptions, but most of the supporting evidence is from the initial episode of care, not the first prescription.


To examine associations between features of the first opioid prescription and high-risk opioid use in the 18 months following the first prescription.


Retrospective cohort study using data from a large commercial insurance claims database for 2011–2014 to identify individuals with no recent use of opioids and follow them for 18 months after the first opioid prescription.


Privately insured patients aged 18–64 and Medicare Advantage patients aged 65 or older who filled a first opioid prescription between 07/01/2011 and 06/30/2013.

Main Outcomes and Measures

High-risk opioid use was measured by having (1) opioid prescriptions overlapping for 7 days or more, (2) opioid and benzodiazepine prescriptions overlapping for 7 days or more, (3) three or more prescribers of opioids, and (4) a daily dosage exceeding 120 morphine milligram equivalents, in each of the six quarters following the first prescription.

Key Results

All three features of the first prescription were strongly associated with high-risk use. For example, among privately insured patients, receiving a long- (vs. short-) acting first opioid was associated with a 16.9-percentage-point increase (95% CI, 14.3–19.5), a daily MME of 50 or more (vs. less than 30) was associated with a 12.5-percentage-point increase (95% CI, 12.1–12.9), and a supply exceeding 7 days (vs. 3 or fewer days) was associated with a 4.8-percentage-point increase (95% CI, 4.5–5.2), in the probability of having a daily dosage of 120 MMEs or more in the long term, compared to a sample mean of 4.2%. Results for the Medicare Advantage patients were similar.


Long-acting formulation, high daily dosage, and longer duration of the first opioid prescription were each associated with increased high-risk use of opioids in the long term.


prescription drug abuse pain health services research physician behavior 


Funding Information

This study was funded by the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH), a National Institute on Drug Abuse Center of Excellence (Grant No. P30DA040500; YB, PJJ, BRS), the National Institute of Mental Health (Grant No. R01MH104200; YB, PJ, PJJ), the National Institute on Aging (Grant Nos. P30AG022845, K24AG053462; MCR), the New York State Health Foundation (Grant No. 17-05047; JSA), the Agency for Healthcare Research and Quality (Grant No. K01HS021531; JSA), and the Weill Cornell Medical College Department of Healthcare Policy and Research (for access to HCCI data).

Compliance with Ethical Standards

This study was approved by the Institutional Review Board of the Weill Cornell Medical College.

Conflict of Interest

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

Supplementary material

11606_2018_4628_MOESM1_ESM.docx (1.8 mb)
ESM 1 (DOCX 1.79 mb)


  1. 1.
    Centers for Disease Control and Prevention, National Center for Health Statistics. Number and age-adjusted rates of drug-poisoning deaths involving opioid analgesics and heroin: United States, 2000-2014. National Vital Statistics System, Mortality File Accessed July 13, 2018.
  2. 2.
    Guy GP, Jr., 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(26):697–704.Google Scholar
  3. 3.
    Shah A, Hayes CJ, Martin BC. Characteristics of initial prescription episodes and likelihood of long-term opioid use — United States, 2006–2015. MMWR Morb Mortal Wkly Rep. 2017;66(10):265–269.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Chou R, Turner JA, Devine EB, et al. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276–286.CrossRefPubMedGoogle Scholar
  5. 5.
    Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain—United States, 2016. JAMA. 2016;315(15):1624–1645.CrossRefPubMedGoogle Scholar
  6. 6.
    Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain — United States, 2016. MMWR Recomm Rep. 2016;65(1):1–49.CrossRefPubMedGoogle Scholar
  7. 7.
    Baker-White A. A look at state legislation limiting opioid prescriptions. 2017; Accessed July 13, 2018.Google Scholar
  8. 8.
    Deyo RA, Hallvik SE, Hildebran C, et al. Association between initial opioid prescribing patterns and subsequent long-term use among opioid-naïve patients: a statewide retrospective cohort study. J Gen Intern Med. 2017;32(1):21–27.CrossRefPubMedGoogle Scholar
  9. 9.
    Brat GA, Agniel D, Beam A, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. BMJ. 2018;360:j5790.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    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(4):608–615.CrossRefPubMedGoogle Scholar
  11. 11.
    Health Care Cost Institute. 2017; Accessed July 13, 2018.
  12. 12.
    United States Census Bureau. American Community Survey. Accessed July 13, 2018.
  13. 13.
    Hollingsworth A, Ruhm CJ, Simon K. Macroeconomic conditions and opioid abuse. NBER Work Pap Ser. 2017;No. 23192.Google Scholar
  14. 14.
    National Center for Injury Prevention and Control. CDC compilation of benzodiazepines, muscle relaxants, stimulants, zolpidem, and opioid analgesics with oral morphine milligram equivalent conversion factors, 2016 version. 2016; Accessed July 13, 2018.
  15. 15.
    Meara E, Horwitz JR, Powell W, et al. State legal restrictions and prescription-opioid use among disabled adults. N Engl J Med. 2016;375(1):44–53.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Prescription Drug Monitoring Program Training and Technical Assistance Center. DEFINITIONS OF PBSS MEASURES. Accessed July 13, 2018.
  17. 17.
    Seal KH, Shi Y, Cohen G, et al. Association of mental health disorders with prescription opioids and high-risk opioid use in US veterans of Iraq and Afghanistan. JAMA. 2012;307(9):940–947.CrossRefPubMedGoogle Scholar
  18. 18.
    Sun EC, Dixit A, Humphreys K, et al. Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis. BMJ. 2017;356:j760.Google Scholar
  19. 19.
    Hawkins EJ, Malte CA, Grossbard JR, Saxon AJ. Prevalence and Trends of Concurrent Opioid Analgesic and Benzodiazepine Use Among Veterans Affairs Patients with Post-traumatic Stress Disorder, 2003-2011. Pain Med. 2015;16(10):1943–1954.CrossRefPubMedGoogle Scholar
  20. 20.
    Braden JB, Russo J, Fan MY, et al. Emergency department visits among recipients of chronic opioid therapy. Arch Intern Med. 2010;170(16):1425–1432.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Wilsey BL, Fishman SM, Gilson AM, et al. Profiling multiple provider prescribing of opioids, benzodiazepines, stimulants, and anorectics. Drug Alcohol Depend. 2010;112(1):99–106.CrossRefPubMedGoogle Scholar
  22. 22.
    Baumblatt J, Wiedeman C, Dunn JR, et al. High-risk use by patients prescribed opioids for pain and its role in overdose deaths. JAMA Intern Med. 2014;174(5):796–801.CrossRefGoogle Scholar
  23. 23.
    Jena AB, Goldman D, Weaver L, Karaca-Mandic P. Opioid prescribing by multiple providers in Medicare: retrospective observational study of insurance claims. BMJ 2014;348:g1393.Google Scholar
  24. 24.
    United States Census Bureau. 2010 Urban Area to ZIP Code Tabulation Area (ZCTA) Relationship File. Accessed July 13, 2018.
  25. 25.
    Stata Statistical Software: Release 14 [computer program]. College Station, TX: StataCorp LP; 2015.Google Scholar
  26. 26.
    White H. A heteroskedasticity-consistent convariance matrix estimator and a direct test for heteroskedasticity. Econometrica. 1980;48:817–830.CrossRefGoogle Scholar
  27. 27.
    Rauck RL. What is the case for prescribing long-acting opioids over short-acting opioids for patients with chronic pain? A critical review. Pain Pract. 2009;9(6):468–479.CrossRefPubMedGoogle Scholar
  28. 28.
    MacQuarrie B. Blue Cross cuts back on painkiller prescriptions: An 18-month effort targets opiate abuse. 2014; Accessed July 13, 2018.Google Scholar
  29. 29.
    Scutti S, Kounang N. CVS will limit opioid prescriptions to 7 days. 2017; Accessed July 13, 2018.Google Scholar
  30. 30.
    Johnson L. Insurance Circular Letter No. 6 (2016) - Coverage for Substance Use Disorder Treatment. 2016; Accessed July 13, 2018.
  31. 31.
    Delgado MK, Shofer FS, Patel MS, et al. Association between electronic medical record implementation of default opioid prescription quantities and prescribing behavior in two emergency departments. J Gen intern Med 2018;33:409.Google Scholar
  32. 32.
    Meeker D, Linder JA, Fox CR, et al. Effect of behavioral interventions on inappropriate antibiotic prescribing among primary care practices: a randomized clinical trial. JAMA. 2016;315(6):562–570.CrossRefPubMedGoogle Scholar

Copyright information

© Society of General Internal Medicine 2018

Authors and Affiliations

  • Yongkang Zhang
    • 1
  • Phyllis Johnson
    • 1
  • Philip J. Jeng
    • 1
  • M. Carrington Reid
    • 2
  • Lisa R. Witkin
    • 3
    • 4
  • Bruce R. Schackman
    • 1
    • 2
    • 5
  • Jessica S. Ancker
    • 1
  • Yuhua Bao
    • 1
    • 5
  1. 1.Department of Healthcare Policy & Research Weill Cornell Medical CollegeNew YorkUSA
  2. 2.Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  3. 3.Department of AnesthesiologyWeill Cornell Medical CollegeNew YorkUSA
  4. 4.Division of Pain MedicineNew York-Presbyterian/Lower Manhattan HospitalNew YorkUSA
  5. 5.Department of PsychiatryWeill Cornell Medical CollegeNew YorkUSA

Personalised recommendations