Factors Influencing Long-Term Opioid Use Among Opioid Naive Patients: An Examination of Initial Prescription Characteristics and Pain Etiologies

  • Anuj Shah
    Division of Pharmaceutical Evaluation and Policy, Department of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas
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  • Corey J. Hayes
    Division of Pharmaceutical Evaluation and Policy, Department of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas

    Division of Health Services Research, Psychiatric Research Institute, University of Arkansas for Medical Sciences College of Medicine, Little Rock, Arkansas
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  • Bradley C. Martin
    Address reprint requests to Bradley C. Martin, PharmD, PhD, Division of Pharmaceutical Evaluation and Policy, University of Arkansas for Medical Sciences, 4301 W Markham St, slot 522, Little Rock, AR 72205.
    Division of Pharmaceutical Evaluation and Policy, Department of Pharmacy Practice, University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas
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      • Patients with chronic pain had the highest probability of continued opioid use.
      • Long-term opioid use was uncommon for other conditions (<7% at 1 year).
      • Initiation with tramadol or long-acting opioids increases likelihood of continued use.
      • The days supplied for the first opioid prescription is the strongest predictor of continued opioid use.


      The relationships between the initial opioid prescription characteristics and pain etiology with the probability of opioid discontinuation were explored in this retrospective cohort study using health insurance claims data from a nationally representative database of commercially insured patients in the United States. We identified 1,353,902 persons aged 14 years and older with no history of cancer or substance abuse, with new opioid use episodes and categorized them into 11 mutually exclusive pain etiologies. Cox proportional hazards models were estimated to identify factors associated with time to opioid discontinuation. After accounting for losses to follow-up, the probability of continued opioid use at 1 year was 5.3% across all subjects. Patients with chronic pain had the highest probability for continued opioid use followed by patients with inpatient admissions. Patients prescribed doses ≥90 morphine milligram equivalents (hazard ratio [HR] = .91; 95% confidence interval [CI], .91–.92), initiated with tramadol (HR = .89; 95% CI, .89–.90) or long-acting opioids (HR = .79; 95% CI, .77–.82) were less likely to discontinue opioids. Increasing days' supply of the first prescription was consistently associated with a lower likelihood of opioid discontinuation (HRs, CIs: 3–4 days' supply = .70, .70–.71; 5–7 days' supply = .48, .47–.48; 8–10 days' supply = .37, .37–.38; 11–14 days' supply = .32, .31–.33; 15–21 days’ supply = .29, .28–.29; ≥22 days supplied = .20, .19–.20). The direction of this relationship was consistent across all pain etiologies. Clinicians should initiate patients with the lowest supply of opioids to mitigate unintentional long-term opioid use.


      This study shows that characteristics of the first opioid prescription, particularly duration of the prescription, are significant predictors of continued opioid use irrespective of the indication for an opioid prescription. These data should encourage prescribers to initiate patients using the minimum effective opioid dose and duration to reduce unintended long-term use and could motivate policies that restrict the initial supply of opioids.

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        • Babalonis S.
        • Lofwall M.R.
        • Nuzzo P.A.
        • Siegel A.J.
        • Walsh S.L.
        Abuse liability and reinforcing efficacy of oral tramadol in humans.
        Drug Alcohol Depend. 2013; 129: 116-124
        • Braden J.B.
        • Fan M.-Y.
        • Edlund M.J.
        • Martin B.C.
        • DeVries A.
        • Sullivan M.D.
        Trends in use of opioids by noncancer pain type 2000-2005 among Arkansas Medicaid and HealthCore enrollees: results from the TROUP study.
        J Pain. 2008; 9: 1026-1035
        • Calcaterra S.L.
        • Yamashita T.E.
        • Min S.-J.
        • Keniston A.
        • Frank J.W.
        • Binswanger I.A.
        Opioid Prescribing at Hospital Discharge Contributes to Chronic Opioid Use.
        J Gen Intern Med. 2016; 31: 478-485
        • Campbell C.I.
        • Weisner C.
        • Leresche L.
        • Ray G.T.
        • Saunders K.
        • Sullivan M.D.
        • Banta-Green C.J.
        • Merrill J.O.
        • Silverberg M.J.
        • Boudreau D.
        • Satre D.D.
        • Von Korff M.
        Age and gender trends in long-term opioid analgesic use for noncancer pain.
        Am J Public Health American Public Health Association. 2010; 100: 2541-2547
        • Centers for Disease Control and Prevention (CDC)
        Vital signs: Overdoses of prescription opioid pain relievers–United States, 1999–2008.
        MMWR Morb Mortal Wkly Rep. 2011; 60: 1487-1492
        • Chou R.
        • Turner J.A.
        • Devine E.B.
        • Hansen R.N.
        • Sullivan S.D.
        • Blazina I.
        • Dana T.
        • Bougatsos C.
        • Deyo R.A.
        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: 276-286
        • Cunningham J.
        • Craner J.
        • Evans M.
        • Hooten W.M.
        Benzodiazepine use in patients with chronic pain in an interdisciplinary pain rehabilitation program.
        J Pain Res Volume. 2017; 10: 311-317
        • Daubresse M.
        • Chang H.-Y.
        • Yu Y.
        • Viswanathan S.
        • Shah N.D.
        • Stafford R.S.
        • Kruszewski S.P.
        • Alexander G.C.
        Ambulatory Diagnosis and Treatment of Nonmalignant Pain in the United States, 2000–2010.
        Med Care. 2013; 51: 870-878
        • Deyo R.A.
        • Hallvik S.E.
        • Hildebran C.
        • Marino M.
        • Dexter E.
        • Irvine J.M.
        • Van Otterloo J.
        • Wright D.A.
        • Leichtling G.
        • Millet L.M.
        Association Between Initial Opioid Prescribing Patterns and Subsequent Long-Term Use Among Opioid-Naive Patients: A Statewide Retrospective Cohort Study.
        J Gen Intern Med. 2017; : 21-27
        • Dowell D.
        • Haegerich T.M.
        • Chou R.
        CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016.
        MMWR Recomm Rep. 2016; 65: 1-49
        • Edlund M.J.
        • Austen M.A.
        • Sullivan M.D.
        • Martin B.C.
        • Williams J.S.
        • Fortney J.C.
        • Hudson T.J.
        Patterns of opioid use for chronic noncancer pain in the Veterans Health Administration from 2009 to 2011.
        Pain. 2014; 155: 2337-2343
        • Edlund M.J.
        • Martin B.C.
        • Devries A.
        • Fan M.-Y.
        • Braden J.B.
        • Sullivan M.D.
        Trends in use of opioids for chronic noncancer pain among individuals with mental health and substance use disorders: the TROUP study.
        Clin J Pain. 2010; 26: 1-8
        • Edlund M.J.
        • Martin B.C.
        • Fan M.Y.
        • Braden J.B.
        • Devries A.
        • Sullivan M.D.
        An analysis of heavy utilizers of opioids for chronic noncancer pain in the TROUP study.
        J Pain Symptom Manage. 2010; 40: 279-289
        • Edlund M.J.
        • Martin B.C.
        • Russo J.E.
        • Devries A.
        • Braden J.B.
        • Sullivan M.D.
        The Role of Opioid Prescription in Incident Opioid Abuse and Dependence Among Individuals with Chronic Non-cancer Pain.
        Clin J Pain. 2013; 30: 1
        • Furlan A.D.
        • Hassan S.
        • Famiyeh I.-M.
        • Wang W.
        • Dhanju J.
        Long-term opioid use after discharge from inpatient musculoskeletal rehabilitation.
        J Rehabil Med. 2016; 48: 464-468
        • Horsfall J.T.
        • Sprague J.E.
        The Pharmacology and Toxicology of the “Holy Trinity”.
        Basic Clin Pharmacol Toxicol. 2017; 120: 115-119
        • Hudson T.J.
        • Edlund M.J.
        • Steffick D.E.
        • Tripathi S.P.
        • Sullivan M.D.
        Epidemiology of regular prescribed opioid use: results from a national, population-based survey.
        J Pain Symptom Manage. 2008; 36: 280-288
        • Hudson T.J.
        • Painter J.T.
        • Martin B.
        • Austen M.A.
        • Williams J.S.
        • Fortney J.
        • Sullivan M.D.
        • Edlund M.E.
        Pharmacoepidemiologic analyses of opioid use among OEF/OIF/OND veterans.
        Pain. 2017; 158: 1039-1045
        • Ivanova J.I.
        • Birnbaum H.G.
        • Schiller M.
        • Kantor E.
        • Johnstone B.M.
        • Swindle R.W.
        Real-world practice patterns, health-care utilization, and costs in patients with low back pain: the long road to guideline-concordant care.
        Spine J. 2011; 11: 622-632
      1. Kelly E, Groppe M: House passing bills to fight opioid addiction. USA Today. 2016. Available from: Accessed June 7, 2016

        • Levy B.
        • Paulozzi L.
        • Mack K.A.
        • Jones C.M.
        Trends in Opioid Analgesic–Prescribing Rates by Specialty, U.S., 2007–2012.
        Am J Prev Med. 2015; 49: 409-413
        • Martin B.C.
        • Fan M.-Y.
        • Edlund M.J.
        • Devries A.
        • Braden J.B.
        • Sullivan M.D.
        Long-term chronic opioid therapy discontinuation rates from the TROUP study.
        J Gen Intern Med. 2011; 26: 1450-1457
        • McDonald D.C.
        • Carlson K.
        • Izrael D.
        Geographic variation in opioid prescribing in the U.S.
        J Pain. 2012; 13: 988-996
        • Morden N.E.
        • Munson J.C.
        • Colla C.H.
        • Skinner J.S.
        • Bynum J.P.W.
        • Zhou W.
        • Meara E.
        Prescription opioid use among disabled Medicare beneficiaries: intensity, trends, and regional variation.
        Med Care. 2014; 52: 852-859
        • Nahin R.L.
        Estimates of Pain Prevalence and Severity in Adults: United States, 2012.
        J Pain. 2015; 16: 769-780
      2. NCSL. National Conference of State Legislatures: Preventing Opioid Misuse: Legislative Trends and Predictions. Available at:, Accessed April 26, 2017.

        • Nielsen S.
        • Lintzeris N.
        • Bruno R.
        • Campbell G.
        • Larance B.
        • Hall W.
        • Hoban B.
        • Cohen M.L.
        • Degenhardt L.
        Benzodiazepine Use among Chronic Pain Patients Prescribed Opioids: Associations with Pain, Physical and Mental Health, and Health Service Utilization.
        Pain Med. 2015; 16: 356-366
        • Paulozzi L.J.
        • Mack K.A.
        • Hockenberry J.M.
        • Division of Unintentional Injury Prevention, National Center for Injury Prevention and Control, CDC
        Vital signs: variation among States in prescribing of opioid pain relievers and benzodiazepines - United States, 2012.
        MMWR Morb Mortal Wkly Rep. 2014; 63: 563-568
        • Richardson L.P.
        • Russo J.E.
        • Katon W.
        • McCarty C.A.
        • DeVries A.
        • Edlund M.J.
        • Martin B.C.
        • Sullivan M.
        Mental health disorders and long-term opioid use among adolescents and young adults with chronic pain.
        J Adolesc Health NIH Public Access. 2012; 50: 553-558
        • Seal K.H.
        • Shi Y.
        • Cohen G.
        • Cohen B.E.
        • Maguen S.
        • Krebs E.E.
        • Neylan T.C.
        Association of mental health disorders with prescription opioids and high-risk opioid use in US veterans of Iraq and Afghanistan.
        JAMA. 2012; 307: 940-947
        • Shah A.
        • Hayes C.J.
        • Martin B.C.
        Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006–2015.
        MMWR Morb Mortal Wkly Rep. 2017; 66: 265-269
      3. “Weak” opioid analgesics. Codeine, dihydrocodeine and tramadol: No less risky than morphine.
        Prescrire Int. 2016; 25: 45-50