The Natural History, Clinical Course, and Long-Term Recovery from Opioid Use Disorders

  • Elizabeth A. EvansEmail author
  • Yih-Ing Hser
Part of the Current Clinical Psychiatry book series (CCPSY)


Studies of the long-term course of opioid use disorder (OUD) underscore how the condition is exacerbated by factors such as interactions with the criminal justice system, limited access to medications to treat OUD, chronic unemployment and conditions of poverty, physical/psychological trauma and related mental illness, social isolation, and poor social support. Developments in pharmacotherapies for OUD and innovative means of administration have yielded important advances in effective medication-based treatments, yet social and political structures remain as obstacles in some regions of the United States and other parts of the world affected by OUD. Changes in perceptions about OUD as a chronic brain disease and about the effectiveness of pharmacotherapies for OUD indicate a public health approach may slowly supersede the criminal justice approach to addressing OUD. This chapter provides an overview of OUD problems as they have emerged and as they are societally and clinically addressed, emphasizing the management and treatment of OUD with effective use of available pharmacotherapies and within environments that are supportive of recovery.


Opioid Heroin Opioid use disorder Heroin use disorder Addiction Natural history Longitudinal Prospective cohort studies Life course Methadone Buprenorphine Naltrexone Long-term recovery 



Dr. Evans is supported by the Greenwall Foundation, the National Institute on Drug Abuse (NIDA) UG3 DA0044830-02S1, and Substance Abuse and Mental Health Services Administration (SAMHSA), Center for Substance Abuse Treatment (CSAT) Grant No. 1H79T1081387-01. Dr. Hser is supported by NIDA R33DA045844 and UG1 DA013035.


  1. 1.
    Hedegaard H, Warner M, Miniño AM. Drug overdose deaths in the United States, 1999-2016, NCHS data brief, no 294. Hyattsville: National Center for Health Statistics; 2017.Google Scholar
  2. 2.
    Case A, Deaton A. Rising morbidity and mortality in midlife among white non-Hispanic Americans in the 21st century. Proc Natl Acad Sci U S A. 2015;112(49):15078–83.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Kochanek KD, Murphy SL, Xu JQ, Arias E. Mortality in the United States, 2016, NCHS data brief, no 293. Hyattsville: National Center for Health Statistics; 2017.Google Scholar
  4. 4.
    U.S. Department of Health and Human Services (HHS). Facing addiction in America: the Surgeon General’s report on alcohol, drugs, and health, vol. 17. Washington, DC: HHS; 2016. p. 6.Google Scholar
  5. 5.
    Rudder M, Tsao L, Jack HE. Shared responsibility: Massachusetts legislators, physicians, and an act relative to substance use treatment, education, and prevention. AMA J Ethics. 2016;18(9):950–9.PubMedCrossRefGoogle Scholar
  6. 6.
    D’Onofrio G, Chawarski MC, O’Connor PG, Pantalon MV, Busch SH, Owens PH, et al. Emergency department-initiated buprenorphine for opioid dependence with continuation in primary care: outcomes during and after intervention. J Gen Intern Med. 2017;32(6):660–6.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Martin A, Mitchell A, Wakeman S, White B, Raja A. Emergency department treatment of opioid addiction: an opportunity to lead. Acad Emerg Med. 2018;25(5):601–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Lee JD, Friedmann PD, Kinlock TW, Nunes EV, Boney TY, Hoskinson RA Jr, et al. Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. N Engl J Med. 2016;374(13):1232–42.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Farabee D, Hillhouse M, Condon T, McCrady B, McCollister K, Ling W. Injectable pharmacotherapy for opioid use disorders (IPOD). Contemp Clin Trials. 2016;49:70–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Hser YI, Anglin MD, Grella C, Longshore D, Prendergast ML. Drug treatment careers: a conceptual framework and existing research findings. J Subst Abus Treat. 1997;14(6):543–58.CrossRefGoogle Scholar
  11. 11.
    Hser YI. Predicting long-term stable recovery from heroin addiction: findings from a 33-year follow-up study. J Addict Dis. 2007;26(1):51–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Hser YI, Evans E, Grella C, Ling W, Anglin D. Long-term course of opioid addiction. Harv Rev Psychiatry. 2015;23(2):76–89.PubMedCrossRefGoogle Scholar
  13. 13.
    Hser YI, Hoffman V, Grella CE, Anglin MD. A 33-year followup of narcotics addicts. Arch Gen Psychiatry. 2001;58(5):503–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Degenhardt L, Bucello C, Mathers B, Briegleb C, Ali H, Hickman M, et al. Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta-analysis of cohort studies. Addiction. 2011;106(1):32–51.PubMedCrossRefGoogle Scholar
  15. 15.
    Hser YI, Mooney LJ, Saxon AJ, Miotto K, Bell DS, Zhu Y, et al. High mortality among patients with opioid use disorder in a large healthcare system. J Addict Med. 2017;11(4):315–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2:CD002207.Google Scholar
  17. 17.
    Bart G. Maintenance medication for opiate addiction: the foundation of recovery. J Addict Dis. 2012;31(3):207–25.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Bell J, Trinh L, Butler B, Randall D, Rubin G. Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment. Addiction. 2009;104(7):1193–200.PubMedCrossRefGoogle Scholar
  19. 19.
    Connock M, Juarez-Garcia A, Jowett S, Frew E, Liu Z, Taylor RJ, et al. Methadone and buprenorphine for the management of opioid dependence: a systematic review and economic evaluation. Health Technol Assess. 2007;11:1–171, iii–iv.PubMedGoogle Scholar
  20. 20.
    Hser YI, Evans E, Huang D, Weiss R, Saxon A, Carroll KM, et al. Long-term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi-site trial. Addiction. 2016;111(4):695–705.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2008;2:CD002207.Google Scholar
  22. 22.
    Evans E, Li L, Min J, Huang D, Urada D, Liu L, et al. Mortality among individuals accessing pharmacological treatment for opioid dependence in California, 2006-10. Addiction. 2015;110(6):996–1005.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Thomas CP, Fullerton CA, Kim M, Montejano L, Lyman DR, Dougherty RH, et al. Medication-assisted treatment with buprenorphine: assessing the evidence. Psychiatr Serv. 2014;65(2):158–70.PubMedCrossRefGoogle Scholar
  24. 24.
    Woody G, Bruce D, Korthuis PT, Chhatre S, Hillhouse M, Jacobs P, et al. HIV risk reduction with buprenorphine-naloxone or methadone: findings from a randomized trial. J Acquir Immune Defic Syndr. 2014;66(3):288–93.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Chi FW, Weisner C, Grella CE, Hser YI, Moore C, Mertens J. Does age at first treatment episode make a difference in outcomes over 11 years? J Subst Abus Treat. 2014;46(4):482–90.CrossRefGoogle Scholar
  26. 26.
    Evans E, Li L, Grella C, Brecht ML, Hser YI. Developmental timing of first drug treatment and 10-year patterns of drug use. J Subst Abus Treat. 2013;44(3):271–9.CrossRefGoogle Scholar
  27. 27.
    Darke S, Ross J, Mills KL, Williamson A, Havard A, Teesson M. Patterns of sustained heroin abstinence amongst long-term, dependent heroin users: 36 months findings from the Australian Treatment Outcome Study (ATOS). Addict Behav. 2007;32(9):1897–906.PubMedCrossRefGoogle Scholar
  28. 28.
    Skinner ML, Haggerty KP, Fleming CB, Catalano RF, Gainey RR. Opiate-addicted parents in methadone treatment: long-term recovery, health, and family relationships. J Addict Dis. 2010;30(1):17–26.CrossRefGoogle Scholar
  29. 29.
    Krebs E, Min JE, Evans E, Li L, Liu L, Huang D, et al. Estimating state transitions for opioid use disorders. Med Decis Mak. 2017;37(5):483–97.CrossRefGoogle Scholar
  30. 30.
    Lee JD, Nunes EV Jr, Novo P, Bachrach K, Bailey GL, Bhatt S, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309–18.PubMedCrossRefGoogle Scholar
  31. 31.
    Burns L, Gisev N, Larney S, Dobbins T, Gibson A, Kimber J, et al. A longitudinal comparison of retention in buprenorphine and methadone treatment for opioid dependence in New South Wales, Australia. Addiction. 2015;110(4):646–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Proctor SL, Copeland AL, Kopak AM, Herschman PL, Polukhina N. A naturalistic comparison of the effectiveness of methadone and two sublingual formulations of buprenorphine on maintenance treatment outcomes: findings from a retrospective multisite study. Exp Clin Psychopharmacol. 2014;22(5):424–33.PubMedCrossRefGoogle Scholar
  33. 33.
    Evans E, Yoo C, Huang D, Hser YI. Effects of access barriers and medication acceptability on buprenorphine-naloxone treatment utilization over 5 years: results from a multisite randomized trial of patients with opioid use disorder. In review 2019.Google Scholar
  34. 34.
    Evans E, Grella C. Gender and mental health comorbidity among adults with opioid use disorders: results from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). Oral presentation, college on problems of drug dependence annual meeting June 2018, San Diego, CA.Google Scholar
  35. 35.
    Evans EA, Grella CE, Washington DL, Upchurch DM. Gender and race/ethnic differences in the persistence of alcohol, drug, and poly-substance use disorders. Drug Alcohol Depend. 2017;174:128–36.PubMedCrossRefGoogle Scholar
  36. 36.
    Scherbaum N, Specka M. Factors influencing the course of opiate addiction. Int J Methods Psychiatr Res. 2008;17(S1):S39–44.PubMedCrossRefGoogle Scholar
  37. 37.
    Darke S. Pathways to heroin dependence: time to re-appraise self-medication. Addiction. 2013;108(4):659–67.PubMedCrossRefGoogle Scholar
  38. 38.
    Hemsing N, Greaves L, Poole N, Schmidt R. Misuse of prescription opioid medication among women: a scoping review. Pain Res Manag. 2016;2016:1754195.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Edlund MJ, Steffick D, Hudson T, Harris KM, Sullivan M. Risk factors for clinically recognized opioid abuse and dependence among veterans using opioids for chronic non-cancer pain. Pain. 2007;129(3):355–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Grella CE, Lovinger K. Gender differences in physical and mental health outcomes among an aging cohort of individuals with a history of heroin dependence. Addict Behav. 2012;37(3):306–12.PubMedCrossRefGoogle Scholar
  41. 41.
    Lalic S, Gisev N, Bell JS, Korhonen MJ, Ilomäki J. Predictors of persistent prescription opioid analgesic use among people without cancer in Australia. Br J Clin Pharmacol. 2018;84(6):1267–78.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Dowell D, Haegerich TM, Chou R. CDC guideline for prescribing opioids for chronic pain-United States, 2016. JAMA. 2016;315(15):1624–45.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hser YI, Mooney LJ, Saxon AJ, Miotto K, Bell DS, Huang D. Chronic pain among patients with opioid use disorder: results from electronic health records data. J Subst Abus Treat. 2017;77:26–30.CrossRefGoogle Scholar
  44. 44.
    Binswanger IA, Blatchford PJ, Mueller SR, Stern MF. Mortality after prison release: opioid overdose and other causes of death, risk factors, and time trends from 1999 to 2009. Ann Intern Med. 2013;159(9):592–600.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Bukten A, Stavseth MR, Skurtveit S, Tverdal A, Strang J, Clausen T. High risk of overdose death following release from prison: variations in mortality during a 15-year observation period. Addiction. 2017;112(8):1432–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Nosyk B, Anglin MD, Brecht ML, Lima VD, Hser YI. Characterizing durations of heroin abstinence in the California civil addict program: results from a 33-year observational cohort study. Am J Epidemiol. 2013;177(7):675–82.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Dasgupta N, Beletsky L, Ciccarone D. Opioid crisis: no easy fix to its social and economic determinants. Am J Public Health. 2018;108(2):182–6.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Wiessing L, Ferri M, Darke S, Simon R, Griffiths P. Large variation in measures used to assess outcomes of opioid dependence treatment: a systematic review of longitudinal observational studies. Drug Alcohol Rev. 2018;37(S1):S323–38.PubMedCrossRefGoogle Scholar
  49. 49.
    Hser YI, Huang D, Saxon AJ, Woody G, Moskowitz AL, Matthews AG, et al. Distinctive trajectories of opioid use over an extended follow-up of patients in a multisite trial on buprenorphine+ naloxone and methadone. J Addict Med. 2017;11(1):63–9.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Zhu Y, Evans EA, Mooney LJ, Saxon AJ, Kelleghan A, Yoo C, Hser YI. Correlates of Long-Term Opioid Abstinence After Randomization to Methadone Versus Buprenorphine/Naloxone in a Multi-Site Trial. J Neuroimmune Pharmacol. 2018;13(4):488–497.PubMedCrossRefGoogle Scholar
  51. 51.
    Grella CE, Lovinger K. 30-year trajectories of heroin and other drug use among men and women sampled from methadone treatment in California. Drug Alcohol Depend. 2011;118(2–3):251–8.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Termorshuizen F, Krol A, Prins M, van Ameijden EJ. Long-term outcome of chronic drug use: the Amsterdam Cohort Study among drug users. Am J Epidemiol. 2005 Feb;161(3):271–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Wang L, Min JE, Krebs E, Evans E, Huang D, Liu L, et al. Polydrug use and its association with drug treatment outcomes among primary heroin, methamphetamine, and cocaine users. Int J Drug Policy. 2017;49:32–40.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Institute of Medicine (US). Committee on Crossing the Quality Chasm: Adaptation to Mental Health and Addictive Disorders. Improving the quality of health care for mental and substance-use conditions. Washington, DC: National Academy Press; 2006.Google Scholar
  55. 55.
    Substance Abuse and Mental Health Services Administration. SAMHSA’s working definition of recovery: 10 guiding principles of recovery. Rockville: SAMHSA; 2012.Google Scholar
  56. 56.
    White WL. Recovery: its history and renaissance as an organizing construct concerning alcohol and other drug problems. Alcohol Treat Q. 2005;23(1):3–15.CrossRefGoogle Scholar
  57. 57.
    White WL. Slaying the dragon: the history of addiction treatment and recovery in America. Bloomington: Chestnut Health Systems/Lighthouse Institute; 1998.Google Scholar
  58. 58.
    White WL. Pre-AA alcoholic mutual aid societies. Alcohol Treat Q. 2001;19(2):1–21.CrossRefGoogle Scholar
  59. 59.
    Humphreys K. Circles of recovery: self-help organizations for addictions. Cambridge: Cambridge University Press; 2004.Google Scholar
  60. 60.
    Maddux JF, Desmond DP. Relapse and recovery in substance abuse careers. NIDA Res Monogr. 1986;72:49–72.PubMedGoogle Scholar
  61. 61.
    Laudet AB, White WL. Recovery capital as prospective predictor of sustained recovery, life satisfaction, and stress among former poly-substance users. Subst Use Misuse. 2008;43(1):27–54.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Sobell LC, Ellingstad TP, Sobell MB. Natural recovery from alcohol and drug problems: methodological review of the research with suggestions for future directions. Addiction. 2000;95(5):749–64.PubMedCrossRefGoogle Scholar
  63. 63.
    Hanninen V, Koski-Jannes A. Narratives of recovery from addictive behaviours. Addiction. 1999;94(12):1837–48.PubMedCrossRefGoogle Scholar
  64. 64.
    McIntosh J, McKeganey N. Addicts’ narratives of recovery from drug use: constructing a non-addict identity. Soc Sci Med. 2000;50(10):1501–10.PubMedCrossRefGoogle Scholar
  65. 65.
    Vigilant LG. “I am still suffering:” the dilemma of multiple recoveries in the lives of methadone maintenance patients. Sociol Spectr. 2008;28(3):278–98.CrossRefGoogle Scholar
  66. 66.
    Laudet AB. The road to recovery: where are we going and how do we get there? Empirically driven conclusions and future directions for service development and research. Subst Use Misuse. 2008;43(12–13):2001–20.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Kaskutas LA, Borkman TJ, Laudet A, Ritter LA, Witbrodt J, Subbaraman MS, et al. Elements that define recovery: the experiential perspective. J Stud Alcohol Drugs. 2014;75(6):999–1010.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Witbrodt J, Kaskutas LA, Grella CE. How do recovery definitions distinguish recovering individuals? Five typologies. Drug Alcohol Depend. 2015;148:109–17.PubMedCrossRefGoogle Scholar
  69. 69.
    Betty Ford Institute Consensus Panel. What is recovery? A working definition from the Betty Ford Institute. J Subst Abus Treat. 2007;33(3):221–8.CrossRefGoogle Scholar
  70. 70.
    McLellan T. What is recovery? Revisiting the Betty Ford Institute Consensus Panel definition: The Betty Ford Consensus Panel and Consultants. J Subst Abuse Treat. 2010;38(2):200–1.PubMedCrossRefGoogle Scholar
  71. 71.
    Cloud W, Granfield R. Conceptualizing recovery capital: expansion of a theoretical construct. Subst Use Misuse. 2008;43(12–13):1971–86.PubMedCrossRefGoogle Scholar
  72. 72.
    Granfield R, Cloud W. Social context and “natural recovery”: the role of social capital in the resolution of drug-associated problems. Subst Use Misuse. 2001;36(11):1543–70.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Health Promotion and Policy, School of Public Health and Health Sciences, University of Massachusetts AmherstAmherstUSA
  2. 2.Integrated Substance Abuse Programs, Semel Institute for Neuroscience and Human Behavior, University of California Los AngelesLos AngelesUSA

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