Relapse Risk Factors in Heroin Addicts Treated with Naltrexone and Naltrexone-Behavioural Psychotherapy

  • Jasmina Knežević Tasić
  • Maša Karleuša Valkanou
  • Borislav Đukanović
  • Dragić Banković
  • Vladimir Janjić
Original Article


To construct a successful treatment model for heroin addiction, it is important to define factors that contribute to relapse. In this translational ambidirectional cohort study, we evaluated 2 groups of heroin addicts that underwent the same therapeutic procedures with different outcomes (133 abstainers and 56 relapsers). The study found a new variable, “relapse marker”, defined by the synergy of the following factors: (a) non-use of tramadol before treatment (p < 0.0005), (b) absence of sense of loss of control over behaviour as a motive for treatment initiation (p = 0.048), (c) use of benzodiazepines in recovery (p < 0.0005), (d) substituting heroin addiction with gambling (p < 0.009), e) younger age (p = 0.012), and (f) explicit parental demand as a treatment motive (p = 0.040). This study reports a mathematical model that predicts relapse and inability to sustain stable abstinence as an outcome of heroin addiction treatment.


Heroin addiction Treatment outcome Relapse Addiction syndrome Treatment motivation 


Compliance with Ethical Standards


All authors were involved in the study design, had full access to the survey data and analyses, and interpreted the data, critically reviewed the manuscript and had full control, including final responsibility for the decision to submit the paper for publication.

Conflict of Interest

The authors declare that they have no competing interests.

Informed Consent and Ethics

Authors confirm that the submitted study was conducted according to the WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. This study has ethics committee approval. All patients gave their informed consent to the anonymous use of their clinical data for this independent study.


  1. Adinoff, B. (2004). Neurobiological processes in drug reward and addiction. Harvard Review of Psychiatry, 12(6), 305–320. doi: 10.1080/10673220490910844.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Allen, T. J., Moeller, F. G., Rhoades, H. M., & Cherek, D. R. (1998). Impulsivity and history of drug dependence. Drug and Alcohol Dependence, 50(2), 137–145.CrossRefPubMedGoogle Scholar
  3. Best, D. W., Ghufran, S., Day, E., Ray, R., & Loaring, J. (2008). Breaking the habit: a retrospective analysis of desistance factors among formerly problematic heroin users. Drug and Alcohol Review, 27(6), 619–624.CrossRefPubMedGoogle Scholar
  4. Boyle, K., Polinksy, J. L., & Hser, Y. I. (2000). Resistance to drug abuse treatment: a comparison of drug users who accept or decline treatment referral assessment. Journal of Drug Issues, 30(3), 555–574.CrossRefGoogle Scholar
  5. Brewer, J. A., & Potenza, M. N. (2008). The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochemical Pharmacology, 75(1), 63–75.CrossRefPubMedGoogle Scholar
  6. Bühringer, G., Kräplin, A., & Behrendt, S. (2012). Universal characteristics and consequences of the addiction syndrome. In H. J. Shaffer (Ed.), APA addiction syndrome handbook (pp. 291–316). Washington: American Psychological Association.Google Scholar
  7. Casavant, L. & Collin, C. (2001). Illegal drug use and crime: a complex relationship Political and Social Affairs Division. Retrieved at
  8. Cavedini, P., Riboldi, G., Keller, R., D’Annucci, A., & Bellodi, L. (2002). Frontal lobe dysfunction in pathological gambling patients. Biological Psychiatry, 51(4), 334–341.CrossRefPubMedGoogle Scholar
  9. Chandler, R. K., Fletcher, B. W., & Volkow, N. D. (2009). Treating drug abuse and addiction in the criminal justice system: Improving public health and safety. The Journal of the American Medical Association, 301(2), 183–190.CrossRefPubMedGoogle Scholar
  10. Darke, S., Williamson, A., Ross, J., Mills, K. L., Havard, A., & Teesson, M. (2007). Patterns of nonfatal heroin overdose over a 3-year period: findings from the Australian treatment outcome study. Journal of Urban Health, 84(2), 283–291.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Dodge, R., Sindelar, J., & Sinha, R. (2005). The role of depressive symptoms in predicting drug abstinence in outpatient substance abuse treatment. Journal of Substance Abuse Treatment, 28, 189–196.CrossRefPubMedGoogle Scholar
  12. Edenberg, H. J., & Foroud, T. (2006). Review: the genetics of alcoholism: identifying specific genes through family studies. Addiction Biology, 11(3–4), 386–396.CrossRefPubMedGoogle Scholar
  13. Enoch, M. A. (2011). The role of early life stress as a predictor for alcohol and drug dependence. Psychopharmacology, 214, 17–31.CrossRefPubMedGoogle Scholar
  14. Ersche, K. D., Turton, A. J., Pradhan, S., Bullmore, E. T., & Robbins, T. W. (2010). Drug addiction endophenotypes: impulsive versus sensation-seeking personality traits. Biological Psychiatry, 68(8), 770–773.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Evans, J. L., Hahn, J. A., Lum, P. J., Stein, E. S., & Page, K. (2009). Predictors of injection drug use cessation and relapse in a prospective cohort of young injection drug users in San Francisco, CA (UFO Study). Drug and Alcohol Dependence, 101(3), 152–157. doi: 10.1016/j.drugalcdep.2008.12.007.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Eysenck, H. J. (1997). Addiction, personality and motivation. Human Psychopharmacology: Clinical and Experimental, 12(S2), S79–S87.CrossRefGoogle Scholar
  17. Fulcher, G. M. (2009). Motherhood and motivation for substance abuse treatment and behavior change. Berkeley, ProQuest, Los Angeles: University of California.Google Scholar
  18. Galvan, A., Hare, T., Parra, C., Penn, J., Voss, H., Glover, G., & Casey, B. J. (2006). Earlier development of the accumbens relative to orbitofrontal cortex might underlie risk-taking behavior in adolescents. Journal of Neuroscience, 26(25), 6885–6892. doi: 10.1523/JNEUROSCI.1062-06.2006.CrossRefPubMedGoogle Scholar
  19. Gluckman, P., Low, F. Franko K. et al. (2011). Improving the transition: reducing social and psychological morbidity during adolescence. A report from the Prime Minister’s Chief Science Advisor. Office of the Prime Minister’s Science Advisory Committee, New Zealand.Google Scholar
  20. Gossop, M., Stewart, D., Browne, N., & Marsden, J. (2002). Factors associated with abstinence, lapse or relapse to heroin use after residential treatment: protective effect of coping responses. Addiction, 97, 1259–1267.CrossRefPubMedGoogle Scholar
  21. Grace, A. A. (2000). The tonic/phasic model of dopamine system regulation and its implications for understanding alcohol and psychostimulant craving. Addiction, 95, S119–S128.CrossRefPubMedGoogle Scholar
  22. Grant, J. E., Potenza, M. N., Weinstein, A., & Gorelick, D. A. (2010). Introduction tobehavioral addictions. The American Journal of Drug and Alcohol Abuse, 36(5), 233–241.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Gyollai, Á. D., Griffiths, M., Barta, C., Vereczkei, A., Urbán, R., Kun, B., & Demetrovics, Z. (2014). The genetics of problem and pathological gambling: a systematic review. Current Pharmaceutical Design, 20(25), 3993–3999.CrossRefPubMedGoogle Scholar
  24. Heinz, A. J., Wu, J., Witkiewitz, K., Epstein, D. H., & Preston, K. L. (2009). Marriage and relationship closeness as predictors of cocaine and heroin use. Addictive Behaviors, 34(3), 258–263. doi: 10.1016/j.addbeh.2008.10.020.CrossRefPubMedGoogle Scholar
  25. Henkel, L.J., (2007). Substance abuse severity, treatment motivation, and criminal thinking factors: predictors of treatment retention with substance abusing parolees in a correctional aftercare program (Psychology Dissertations). Philadelphia College of Osteopathic Medicine, paper 61.Google Scholar
  26. Hser, Y. I. (2007). Predicting long-term stable recovery from heroin addiction: Findings from a 33-year follow-up study. Journal of Addiction Disorders, 26(1), 51–60.CrossRefGoogle Scholar
  27. Ibáñez, A., Blanco, C., de Castro, I. P., Fernandez-Piqueras, J., & Sáiz-Ruiz, J. (2003). Genetics of pathological gambling. Journal of Gambling Studies, 19(1), 11–22.CrossRefPubMedGoogle Scholar
  28. James, L. (2012). Understanding the process of recovery from heroin addiction: initiating and maintaining factors (Unpublished doctoral dissertation). Cardiff University and the South Wales.Google Scholar
  29. Knežević-Tasić, J., & Đukanović, B. (2015). Bihevioralne zavisnosti u Srbiji. Beograd: Izdavačka knjižarnica Zorana Stojanovića.Google Scholar
  30. Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology, 35(1), 217–238. doi: 10.1038/npp.2009.110.CrossRefPubMedGoogle Scholar
  31. Koob, G. F., Ahmed, S. H., Boutrel, B., et al. (2004). Neurobiological mechanisms in the transition from drug use to drug dependence. Neuroscience Biobehavior Review, 27, 739–749.CrossRefGoogle Scholar
  32. Kosten, T. A., Ball, S. A., & Rounsaville, B. J. (1994). A sibling study of sensation seeking and opiate addiction. Journal of Nervous and Mental Disease, 182(5), 284–289.CrossRefPubMedGoogle Scholar
  33. Krupitsky, E., Zvartau, E., Masalov, D., Tsoi, M., Burakov, A., Egorova, V., Didenko, T., Romanova, T., Ivanova, E., Bespalov, A., Verbitskaya, E., Neznanov, N., Grinenko, A., O'Brien, C., & Woody, G. (2004). Naltrexone for heroin dependence treatment in St. Petersburg, Russia. Journal of Substance Abuse Treatment, 26(4), 285–294.CrossRefPubMedGoogle Scholar
  34. Lin, S. S., & Tsai, C. C. (2002). Sensation seeking and internet dependence of Taiwanese high school adolescents. Computers in Human Behavior, 18(4), 411–426.CrossRefGoogle Scholar
  35. Lobo, D. S., & Kennedy, J. L. (2006). The genetics of gambling and behavioural addictions. CNS Spectrums, 11(12), 931–939.CrossRefPubMedGoogle Scholar
  36. McKay, J. R., Rutherford, M. J., Alterman, A. I., et al. (1995). An examination of the cocaine relapse process. Drug Alcohol Dependance, 38, 35–43.CrossRefGoogle Scholar
  37. Miller, W. R., & Rollnick, S. (2012). Motivational interviewing: helping people change. Guilford press.Google Scholar
  38. National Institute on Drug Abuse (2010). Comorbidity: addiction and other mental illnesses–in-depth report on co-occurring drug use and other mental disorders. Retrieved at
  39. Pavlović, Z., & Jakovljević, B. (2008). Učestalost i faktori rizika od upotrebe psihoaktivnih supstancija kod mladih. Vojnosanitetski Pregled, 65(6), 441–448.CrossRefPubMedGoogle Scholar
  40. Prochaska, J. O., & DiClemente, C. C. (1984). The transtheoretic approach: crossing traditional boundaries of therapy. Homewood, Illinois: Dow Jones/Irwin.Google Scholar
  41. Prochaska, J. O., & DiClemente, C. C. (1992). The trans-theoretical approach. In J. C. Norcross & M. R. Goldfried (Eds.), Handbook of psychotherapy integration (pp. 330–334). New York: Basic Books, Inc..Google Scholar
  42. Rapp, R. C., Siegel, H. A., & DeLiberty, R. N. (2003). Demographic and clinical correlates of client motivation among substance abusers. Health & Social Work, 28(2), 107–115.CrossRefGoogle Scholar
  43. Schmitz, J., Stotts, A., Rhoades, H., & Grabowski, J. (2001). Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addictive Behaviors., 26(2), 167–180.CrossRefPubMedGoogle Scholar
  44. Schuckit, M. A. (2009). An overview of genetic influences in alcoholism. Journal of Substance Abuse Treatment, 36(1), 5–14.Google Scholar
  45. Shaffer, H. (2012). APA Addiction Syndrome Handbook: Foundations, Influences, and Expressions of Addiction, Vol 1. Washington, DC: American Psychological Association.Google Scholar
  46. Shaffer, H. J., LaPlante, D. A., LaBrie, R. A., Kidman, R. C., Donato, A. N., & Stanton, M. V. (2004). Toward a syndrome model of addiction: multiple expressions, common etiology. Harvard Review Psychiatry, 12(6), 367–374.CrossRefGoogle Scholar
  47. Sinha, R. (2001). How does stress increase risk of drug abuse and relapse? Psychopharmacology, 158, 343–359.CrossRefPubMedGoogle Scholar
  48. Sinha, R. (2008). Chronic stress, drug use, and vulnerability to addiction. Annals of the New York Academy of Sciences, 1141, 105–130. doi: 10.1196/annals.1441.030.CrossRefPubMedPubMedCentralGoogle Scholar
  49. Sinha, R. (2011). New findings on biological factors predicting addiction relapse vulnerability. Current Psychiatry Reports, 13(5), 398–405. doi: 10.1007/s11920-011-0224-0.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Tsogia, D., Capello, A., & Orford, J. (2001). Entering treatment for substance misuse: a review of the literature. Journal of Mental Health, 10(5), 481–499.CrossRefGoogle Scholar
  51. Ubale, V. M., Jaju, J. B., Gosavi, P. A., Pawar, G. R., Dharmadhikari, S. C., & Parekar, S. M. (2015). Evaluation of antidepressant activity of tramadol in mice: an experimental study. International Journal of Basic & Clinical Pharmacology, 4(3), 463–468. doi: 10.18203/2319-2003.ijbcp20150017.CrossRefGoogle Scholar
  52. United Nations Office on Drugs and Crime (2013). Opioid overdose: preventing and reducing opioid overdose mortality. United Nations Office at Vienna. Retrieved at Accessed 27 Oct 2015.
  53. United Nations Office on Drugs and Crime (2015). World drug report 2015. United Nations Office at Vienna.Google Scholar
  54. United Nations Office for Drug and Crime (2016). UNODC-WHO The International Standards for the Treatment of Drug Use Disorders. Retrieved at
  55. UNODC, Addiction, Crime and Insurgency (2009). Heroin. Retrieved at
  56. Volkow, N. D., Wang, G. J., Fowler, J. S., Franceschi, D., Thanos, P. K., Wong, C., et al. (2000). Cocaine abusers show a blunted response to alcohol intoxication in limbic brain regions. Life Science, 66, PL161–PL167.CrossRefGoogle Scholar
  57. Zule, P., Lam, W. K. K., & Wechsberg, W. M. (2003). Treatment readiness among out-of-treatment African-American crack users. Journal of Psychoactive Drugs, 35(4), 502–510.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Clinic for Addiction and Other Psychiatric DisordersLorijen HospitalBelgradeSerbia
  2. 2.Institute of Mental Health “Reverie”BelgradeSerbia
  3. 3.University of Donja GoricaPodgoricaMontenegro
  4. 4.Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  5. 5.Faculty of Medical SciencesUniversity of KragujevacKragujevacSerbia

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