Advertisement

Nonopioid Substance Use Disorders and Opioid Dose Predict Therapeutic Opioid Addiction

Published:November 08, 2014DOI:https://doi.org/10.1016/j.jpain.2014.10.011

      Highlights

      • In a pain rehabilitation program, participants with a history of a nonopioid substance use disorder had 28 times the odds of having an addiction to prescribed medications
      • Each 50-mg increase in daily opioid dose approximately doubled the odds of therapeutic opioid addiction.
      • Opioid dosage can be used as an indicator of addiction with moderate accuracy.
      • The daily opioid dose that should prompt addiction screening is surprisingly low.

      Abstract

      Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment.

      Perspective

      This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Agency Medical Directors Group: Intragency Guidelines on Opioid Dosing for Chronic Non-cancer Pain: An Educational Aid to Improve Care and Safety With Opioid Therapy. 2010. Available at: http://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Accessed March 1, 2012

        • American Academy of Pain Medicine
        • the American Pain Society and the American Society of Addiction Medicine
        Definitions related to the use of opioids for the treatment of pain.
        WMJ. 2001; 100: 28-29
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders (4th edition, text revision).
        American Psychiatric Association, Washington, DC2000
        • Andrade S.E.
        • Kahler K.H.
        • Frech F.
        • Chan K.A.
        Methods for evaluation of medication adherence and persistence using automated databases.
        Pharmacoepidemiol Drug Saf. 2006; 15: 565-577
        • Bartleson J.D.
        Evidence for and against the use of opioid analgesics for chronic nonmalignant low back pain: A review.
        Pain Med. 2002; 3: 260-271
        • Berg W.A.
        • Blume J.D.
        • Cormack J.B.
        • Mendelson E.B.
        • Lehrer D.
        • Böhm-Vélez M.
        • Pisano E.D.
        • Jong R.A.
        • Evans W.P.
        • Morton M.J.
        • Mahoney M.C.
        • Larsen L.H.
        • Barr R.G.
        • Farria D.M.
        • Marques H.S.
        • Boparai K.
        ACRIN 6666 investigators: Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer.
        JAMA. 2008; 299: 2151-2163
        • Caudill-Slosberg M.A.
        • Schwartz L.M.
        • Woloshin S.
        Office visits and analgesic prescriptions for musculoskeletal pain in US: 1980 vs. 2000.
        Pain. 2004; 109: 514-519
      2. Cephalon: Actiq [package insert]. 2011. Available at: http://www.actiq.com/pdf/actiq_package_insert_4_5_07.pdf. Accessed March 15, 2012

      3. Cephalon: Fentora [package insert]. 2011. Available at: http://www.fentora.com/pdfs/pdf100_prescribing_info.pdf. Accessed March 15, 2012

        • Chen Y.-W.
        • Barson J.R.
        • Chen A.
        • Hoebel B.G.
        • Leibowitz S.F.
        Opioids in the perifornical lateral hypothalamus suppress ethanol drinking.
        Alcohol. 2013; 47: 31-38
        • Chiang C.N.
        • Hawks R.L.
        Pharmacokinetics of the combination tablet of buprenorphine and naloxone.
        Drug Alcohol Depend. 2003; 70: S39-S47
        • Chou R.
        • Fanciullo G.J.
        • Fine P.G.
        • Adler J.A.
        • Ballantyne J.C.
        • Davies P.
        • Donovan M.I.
        • Fishbain D.A.
        • Foley K.M.
        • Fudin J.
        • Gilson A.M.
        • Kelter A.
        • Mauskop A.
        • O'Connor P.G.
        • Passik S.D.
        • Pasternak G.W.
        • Portenoy R.K.
        • Rich B.A.
        • Roberts R.G.
        • Todd K.H.
        • Miaskowski C.
        American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain.
        J Pain. 2009; 10: 113-130
        • Cleary P.D.
        • Miller M.
        • Bush B.T.
        • Warburg M.M.
        • Delbanco T.L.
        • Aronson M.D.
        Prevalence and recognition of alcohol abuse in a primary care population.
        Am J Med. 1988; 85: 466-471
        • Cohen J.
        A power primer.
        Psychol Bull. 1992; 112: 155-159
        • De Conno F.
        • Groff L.
        • Brunelli C.
        • Zecca E.
        • Ventafridda V.
        • Ripamonti C.
        Clinical experience with oral methadone administration in the treatment of pain in 196 advanced cancer patients.
        J Clin Oncol. 1996; 14: 2836-2842
        • Doyle D.
        • Woodruff R.
        The IAHCP Manual of Palliative Care.
        2nd ed. 2008 (Available at:) (Accessed March 15, 2012)
        • Edlund M.J.
        • Steffick D.
        • Hudson T.
        • Harris K.M.
        • Sullivan M.
        Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain.
        Pain. 2007; 129: 355-362
        • Ekholm O.
        • Grønbaek M.
        • Peuckmann V.
        • Sjøgren P.
        Alcohol and smoking behavior in chronic pain patients: The role of opioids.
        Eur J Pain. 2009; 13: 606-612
        • Faul F.
        • Erdfelder E.
        • Buchner A.
        • Lang A.-G.
        Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses.
        Behav Res Methods. 2009; 41: 1149-1160
        • Faul F.
        • Erdfelder E.
        • Lang A.-G.
        • Buchner A.
        G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences.
        Behav Res Methods. 2007; 39: 175-191
        • Fischer J.E.
        • Bachmann L.M.
        • Jaeschke R.
        A readers' guide to the interpretation of diagnostic test properties: Clinical example of sepsis.
        Intensive Care Med. 2003; 29: 1043-1051
        • Fishbain D.A.
        • Cole B.
        • Lewis J.
        • Rosomoff H.L.
        • Rosomoff R.S.
        What percentage of chronic nonmalignant pain patients exposed to chronic opioid analgesic therapy develop abuse/addiction and/or aberrant drug-related behaviors? A structured evidence-based review.
        Pain Med. 2008; 9: 444-459
        • Hall A.J.
        • Logan J.E.
        • Toblin R.L.
        • Kaplan J.A.
        • Kraner J.C.
        • Bixler D.
        • Crosby A.E.
        • Paulozzi L.J.
        Patterns of abuse among unintentional pharmaceutical overdose fatalities.
        JAMA. 2008; 300: 2613-2620
        • Hausmann L.R.M.
        • Gao S.
        • Lee E.S.
        • Kwoh C.K.
        Racial disparities in the monitoring of patients on chronic opioid therapy.
        Pain. 2013; 154: 46-52
        • Højsted J.
        • Ekholm O.
        • Kurita G.P.
        • Juel K.
        • Sjøgren P.
        Addictive behaviors related to opioid use for chronic pain: A population-based study.
        Pain. 2013; 154: 2677-2683
      4. Hospira: Talwin [package insert]. 2011. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=46353. Accessed March 15, 2012

        • Huffman K.L.
        • Sweis G.W.
        • Gase A.
        • Scheman J.
        • Covington E.C.
        Opioid use 12 months following interdisciplinary pain rehabilitation with weaning.
        Pain Med. 2013; 14: 1908-1917
        • Hunink M.G.
        • Richardson D.K.
        • Doubilet P.M.
        • Begg C.B.
        Testing for fetal pulmonary maturity: ROC analysis involving covariates, verification bias, and combination testing.
        Med Decis Making. 1990; 10: 201-211
        • IBM Corp
        IBM SPSS Statistics for Windows, Version 20.0.
        IBM Corp, Armonk, NY2011
        • Janssen Pharmaceuticals
        Nyucenta - Equianalgesic dosing.
        2012
      5. Joint Pharmacy and Therapeutics Committee of Mercy Medical Center and St. Luke's Hospital: Equianalgesic dose of opioid drugs. 2004. Available at: http://www.crjointpt.com/library/opioid.pdf. Accessed March 15, 2012

        • Joranson D.E.
        • Ryan K.M.
        • Gilson A.M.
        • Dahl J.L.
        Trends in medical use and abuse of opioid analgesics.
        JAMA. 2000; 283: 1710-1714
        • Kuehn B.M.
        Opioid prescriptions soar: Increase in legitimate use as well as abuse.
        JAMA. 2007; 297: 249-253
        • McLellan A.
        • Turner B.
        Prescription opioids, overdose deaths, and physician responsibility.
        JAMA. 2008; 300: 2672-2673
        • Mendelson J.
        • Jones R.T.
        • Welm S.
        • Baggott M.
        • Fernandez I.
        • Melby A.K.
        • Nath R.P.
        Buprenorphine and naloxone combinations: The effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers.
        Psychopharmacology (Berl). 1999; 141: 37-46
        • Michna E.
        • Ross E.L.
        • Hynes W.L.
        • Nedeljkovic S.S.
        • Soumekh S.
        • Janfaza D.
        • Palombi D.
        • Jamison R.N.
        Predicting aberrant drug behavior in patients treated for chronic pain: Importance of abuse history.
        J Pain Symptom Manage. 2004; 28: 250-258
        • Mitchell A.J.
        • Meader N.
        • Bird V.
        • Rizzo M.
        Clinical recognition and recording of alcohol disorders by clinicians in primary and secondary care: Meta-analysis.
        Br J Psychiatry. 2012; 201: 93-100
        • Morasco B.J.
        • Duckart J.P.
        • Carr T.P.
        • Deyo R.A.
        • Dobscha S.K.
        Clinical characteristics of veterans prescribed high doses of opioid medications for chronic non-cancer pain.
        Pain. 2010; 151: 625-632
      6. Moses S: Narcotic Analgesics: Family Practice Notebook. 2009. Available at: http://www.fpnotebook.com/Pharm/Analgesic/NrctcAnlgsc.htm. Accessed March 1, 2012

        • Mushlin A.I.
        • Detsky A.S.
        • Phelps C.E.
        • O'Connor P.W.
        • Kido D.K.
        • Kucharczyk W.
        • Giang D.W.
        • Mooney C.
        • Tansey C.M.
        • Hall W.J.
        • Goodman A.D.
        • Joy S.E.
        • Ketonen L.M.
        • Mattson D.H.
        • Schiffer R.B.
        • Gray T.A.
        • Lambert C.D.
        • Morgenthau D.R.
        • Sawa G.M.J.
        • Smith D.N.
        • Bayer N.H.
        • Goldstein W.C.
        • Gordon A.S.
        • Guttman M.
        • Levitan M.D.
        • Ranalli P.J.
        • Shandling M.R.
        • Silver F.L.
        • Tyndel F.J.
        • Yufe R.S.
        • Joy S.E.
        • Aggarwal S.
        • Kumar A.
        • Lee K.
        • Montanera W.
        • Poon P.
        • Ma G.
        • Grow V.M.
        • Tansey C.M.
        The accuracy of magnetic resonance imaging in patients with suspected multiple sclerosis.
        JAMA. 1993; 269: 3146-3151
        • Nava F.
        • Manzato E.
        • Leonardi C.
        • Lucchini A.
        Opioid maintenance therapy suppresses alcohol intake in heroin addicts with alcohol dependence: Preliminary results of an open randomized study.
        Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 1867-1872
        • Noble M.
        • Treadwell J.R.
        • Tregear S.J.
        • Coates V.H.
        • Wiffen P.J.
        • Akafomo C.
        • Schoelles K.M.
        Long-term opioid management for chronic noncancer pain.
        Cochrane Database Syst Rev. 2010; : CD006605
        • Okie S.
        A flood of opioids, a rising tide of deaths.
        N Engl J Med. 2010; 363 (Erratum in: N Engl J Med Jan 20;364:290, 2011): 1981-1985
        • Paulozzi L.J.
        • Budnitz D.S.
        • Xi Y.
        Increasing deaths from opioid analgesics in the United States.
        Pharmacoepidemiol Drug Saf. 2006; 15: 618-627
        • Polatin P.B.
        • Kinney R.K.
        • Gatchel R.J.
        • Lillo E.
        • Mayer T.G.
        Psychiatric illness and chronic low-back pain. The mind and the spine—which goes first?.
        Spine. 1993; 18: 66-71
        • Potter J.S.
        • Hennessy G.
        • Borrow J.A.
        • Greenfield S.F.
        • Weiss R.D.
        Substance use histories in patients seeking treatment for controlled-release oxycodone dependence.
        Drug Alcohol Depend. 2004; 76: 213-215
      7. Purdue Pharma: Oxycontin. 2012. Available at: http://www.purduepharma.com/pi/prescription/oxycontin.pdf. Accessed March 12, 2012

        • R Core Team
        R: A Language and Environment for Statistical Computing.
        R Foundation for Statistical Computing, Vienna, Austria2013 (Available at:) (Accessed January 14, 2014)
      8. Reckitt Benckiser Pharmaceuticals Inc: Buprenex (Buprenorphrine Hydrochloride). 2005. Available at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b086772e-d15a-4d13-b1a2-38bfbde1f18c. Accessed March 8, 2012

        • Reid M.C.
        • Engles-Horton L.L.
        • Weber M.B.
        • Kerns R.D.
        • Rogers E.L.
        • O'Connor P.G.
        Use of opioid medications for chronic noncancer pain syndromes in primary care.
        J Gen Intern Med. 2002; 17: 173-179
        • Robin X.
        • Turck N.
        • Hainard A.
        • Tiberti N.
        • Lisacek F.
        • Sanchez J.C.
        • Müller M.
        pROC: An open-source package for R and S+ to analyze and compare ROC curves.
        BMC Bioinformatics. 2011; 12: 77
        • Roth S.H.
        • Fleischmann R.M.
        • Burch F.X.
        • Dietz F.
        • Bockow B.
        • Rapoport R.J.
        • Rutstein J.
        • Lacouture P.G.
        Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: Placebo-controlled trial and long-term evaluation.
        Arch Intern Med. 2000; 160: 853-860
        • Schieffer B.M.
        • Pham Q.
        • Labus J.
        • Baria A.
        • Van Vort W.
        • Davis P.
        • Davis F.
        • Naliboff B.D.
        Pain medication beliefs and medication misuse in chronic pain.
        J Pain. 2005; 6: 620-629
      9. US Veteran's Administration and Stanford University Medical School: End of Life Curriculum Project. 2012. Available at: http://endoflife.stanford.edu/M11_pain_control/equivalency_table.html. Accessed March 15, 2012

        • Warner M.
        • Chen L.H.
        • Makuc D.M.
        Increase in fatal poisonings involving opioid analgesics in the United States, 1999-2006.
        NCHS Data Brief. 2009; 22: 1-8
        • Wasan A.D.
        • Correll D.J.
        • Kissin I.
        • O'Shea S.
        • Jamison R.N.
        Iatrogenic addiction in patients treated for acute or subacute pain: A systematic review.
        J Opioid Manag. 2006; 2: 16-22
        • Weisner C.M.
        • Campbell C.I.
        • Ray G.T.
        • Saunders K.
        • Merrill J.O.
        • Banta-Green C.
        • Sullivan M.D.
        • Silverberg M.J.
        • Mertens J.R.
        • Boudreau D.
        • Von Korff M.
        Trends in prescribed opioid therapy for non-cancer pain for individuals with prior substance use disorders.
        Pain. 2009; 145: 287-293
        • Youden W.J.
        Index for rating diagnostic tests.
        Cancer. 1950; 3: 32-35
        • Zhou X.-H.
        • Obuchowski N.A.
        • McClish D.K.
        Statistical Methods in Diagnostic Medicine.
        John Wiley & Sons, New York2011