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CNS Drugs

, Volume 30, Issue 8, pp 719–733 | Cite as

Naltrexone: A Pan-Addiction Treatment?

  • Elias AboujaoudeEmail author
  • Wael O. Salame
Review Article

Abstract

Addiction is a major public health problem with few efficacious and safe treatments. The goal of this review is to provide an evidence-based assessment of the therapeutic role of the opioid antagonist naltrexone across the addiction spectrum—substance-based and behavioral. The PubMed database was searched for randomized, placebo-controlled clinical trials that investigated the oral or intramuscular long-acting formulation of naltrexone in substance use disorders or behavioral addictions such as pathological gambling, kleptomania, and trichotillomania. Thirty-nine efficacy studies were retrieved, covering alcohol use disorder (n = 22), opioid use disorder (n = 6), nicotine use disorder (n = 5), stimulant use disorder (n = 2), gambling disorder (n = 2), trichotillomania (n = 1), and kleptomania (n = 1). Despite the very different presentations within and between both addiction categories, the data, as a whole, show consistency in favor of naltrexone’s relative efficacy and safety. Given the potential benefit and good tolerability revealed in the studies, the high morbidity associated with addiction, and the dearth of alternate treatments, naltrexone would seem like an underutilized treatment option. Further, naltrexone’s seemingly broad anti-addiction efficacy supports a shared role for brain opioid pathways in the pathophysiology of addiction, broadly defined. More studies investigating the efficacy and tolerability of naltrexone and other opioid modulators are warranted. Studies should also further examine the effect of combining psychotherapy with naltrexone, as well as the potential role of naltrexone in treating comorbid addictions.

Keywords

Naltrexone Pathological Gambling Gambling Disorder South Oaks Gambling Screen Behavioral Addiction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

Conflict of interest

Dr. Aboujaoude and Dr. Salame declare that they have no conflict of interest.

Funding

The authors received no funding to prepare this review.

References

  1. 1.
    Moore EA, Wilkinson S. The promise of low dose naltrexone therapy, potential benefits in cancer, autoimmune, neurological and infectious disorders. McFarland; 2008. http://www.elainemoore.com/Books/NEWThePromiseofLDNTherapy/tabid/102/Default.aspx. Last visited 27 Feb 2016.
  2. 2.
    Food and Drug Association. Revia label and approval history. FDA Website. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#labelinfo. Last visited 27 Feb 2016.
  3. 3.
  4. 4.
    Therapeutic Goods Administration. https://search.tga.gov.au/s/search.html?collection=tga-websites-web&query=naltrexone. Last visited 4 Jun 2016.
  5. 5.
    Schecter AJ, Friedman JG, Grossman DJ. Clinical use of naltrexone (EN-1639A): part I: safety and efficacy in pilot studies. Am J Drug Alcohol Abuse. 1974;1(2):253–69.CrossRefPubMedGoogle Scholar
  6. 6.
    Unterwald EM. Naltrexone in the treatment of alcohol dependence. J Addict Med. 2008;2(3):121–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Burattini C, Burbassi S, Aicardi G, Cervo L. Effects of naltrexone on cocaine- and sucrose-seeking behaviour in response to associated stimuli in rats. Int J Neuropsychopharmacol. 2008;11(1):103–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Murray JE, Belin-rauscent A, Simon M, et al. Basolateral and central amygdala differentially recruit and maintain dorsolateral striatum-dependent cocaine-seeking habits. Nat Commun. 2015;6:10088.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    D’souza MS, Markou A. Neuronal mechanisms underlying development of nicotine dependence: implications for novel smoking-cessation treatments. Addict Sci Clin Pract. 2011;6(1):4–16.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Food and Drug Administration. Revia drug insert. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/018932s017lbl.pdf. Last visited 4 Jun 2016.
  11. 11.
    Food and Drug Administration. Vivitrol drug insert. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021897s020s023lbl.pdf. Last visited 25 Feb 2016.
  12. 12.
    Gastfriend DR. Intramuscular extended-release naltrexone: current evidence. Ann N Y Acad Sci. 2011;1216:144–66.CrossRefPubMedGoogle Scholar
  13. 13.
    Potenza MN. Should addictive disorders include non-substance-related conditions? Addiction. 2006;101(Suppl):142–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Petry NM. Should the scope of addictive behaviors be broadened to include pathological gambling? Addiction. 2006;101(S1):152–60.CrossRefPubMedGoogle Scholar
  15. 15.
    Blanco C, Moreyra P, Nunes EV, et al. Pathological gambling: addiction or obsession? Semin Clin Neuropsychiatry. 2001;6:167–76.CrossRefPubMedGoogle Scholar
  16. 16.
    Potenza MN, Fiellin DA, Heninger GR, et al. Gambling: an addictive behavior with health and primary care implications. J Gen Int Med. 2002;17:721–32.CrossRefGoogle Scholar
  17. 17.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1987.Google Scholar
  18. 18.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.Google Scholar
  19. 19.
    Aboujaoude E. Problematic Internet use: an overview. World Psychiatry. 2010;9(2):85–90.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Aboujaoude E. Compulsive buying disorder: a review and update. Curr Pharm Des. 2014;20(25):4021–5.CrossRefPubMedGoogle Scholar
  21. 21.
    Verdejo-garcía A, Lawrence AJ, Clark L. Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neurosci Biobehav Rev. 2008;32(4):777–810.CrossRefPubMedGoogle Scholar
  22. 22.
    Hou H, Tian M, Zhang H. Positron emission tomography molecular imaging of dopaminergic system in drug addiction. Anat Rec (Hoboken). 2012;295(5):722–33.CrossRefPubMedGoogle Scholar
  23. 23.
    Limbrick-Oldfield EH, Van Holst RJ, Clark L. Fronto-striatal dysregulation in drug addiction and pathological gambling: consistent inconsistencies? Neuroimage Clin. 2013;2:385–93.Google Scholar
  24. 24.
    Luijten M, Machielsen MW, Veltman DJ, Hester R, De Haan L, Franken IH. Systematic review of ERP and fMRI studies investigating inhibitory control and error processing in people with substance dependence and behavioural addictions. J Psychiatry Neurosci. 2014;39(3):149–69.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Olmstead MC, Ouagazzal AM, Kieffer BL. Mu and delta opioid receptors oppositely regulate motor impulsivity in the signaled nose poke task. PLoS ONE. 2009;4(2):e4410.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Mick I, Myers J, Ramos AC, et al. Blunted endogenous opioid release following an oral amphetamine challenge in pathological gamblers. Neuropsychopharmacology. 2016;41(7):1742–50.Google Scholar
  27. 27.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.Google Scholar
  28. 28.
    Volpicelli JR, Alterman AI, Hayashida M, O’brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992;49(11):876–80.CrossRefPubMedGoogle Scholar
  29. 29.
    O’Malley SS, Jaffe AJ, Chang G, et al. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry. 1992;49(11):881–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Kranzler HR, Tennen H, Armeli S, et al. Targeted naltrexone for problem drinkers. J Clin Psychopharmacol. 2009;29(4):350–7.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    O’Malley SS, Corbin WR, Leeman RF, et al. Reduction of alcohol drinking in young adults by naltrexone: a double-blind, placebo-controlled, randomized clinical trial of efficacy and safety. J Clin Psychiatry. 2015;76(2):e207–13.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Latt NC, Jurd S, Houseman J, et al. Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness in a standard clinical setting. Med J Aust. 2002;176(11):530–4.PubMedGoogle Scholar
  33. 33.
    Kranzler HR, Armeli S, Tennen H, et al. Targeted naltrexone for early problem drinkers. J Clin Psychopharmacol. 2003;23(3):294–304.PubMedGoogle Scholar
  34. 34.
    Ahmadi J, Kampman KM, Oslin DM, et al. Predictors of treatment outcome in outpatient cocaine and alcohol dependence treatment. Am J Addict. 2009;18(1):81–6.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Morris PL, Hopwood M, Whelan G, Gardiner J, Drummond E. Naltrexone for alcohol dependence: a randomized controlled trial. Addiction. 2001;96(11):1565–73.CrossRefPubMedGoogle Scholar
  36. 36.
    Guardia J, Caso C, Arias F, et al. A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol-dependence disorder: results from a multicenter clinical trial. Alcohol Clin Exp Res. 2002;26(9):1381–7.CrossRefPubMedGoogle Scholar
  37. 37.
    Heinälä P, Alho H, Kiianmaa K, et al. Targeted use of naltrexone without prior detoxification in the treatment of alcohol dependence: a factorial double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2001;21(3):287–92.CrossRefPubMedGoogle Scholar
  38. 38.
    Hernandez-Avila CA, Song C, Kuo L, et al. Targeted versus daily naltrexone: secondary analysis of effects on average daily drinking. Alcohol Clin Exp Res. 2006;30(5):860–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Krystal JH, Cramer JA, Krol WF, et al. Veterans Affairs Naltrexone Cooperative Study 425 Group. Naltrexone in the treatment of alcohol dependence. N Engl J Med. 2001;345(24):1734–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Killeen TK, Brady KT, Gold PB, et al. Effectiveness of naltrexone in a community treatment program. Alcohol Clin Exp Res. 2004;28(11):1710–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Knox PC, Donovan DM. Using naltrexone in inpatient alcoholism treatment. J Psychoactive Drugs. 1999;31(4):373–88.CrossRefPubMedGoogle Scholar
  42. 42.
    Chick J, Anton R, Checinski K, et al. A multicentre, randomized, double-blind, placebo-controlled trial of naltrexone in the treatment of alcohol dependence or abuse. Alcohol Alcohol. 2000;35(6):587–93.CrossRefPubMedGoogle Scholar
  43. 43.
    Huang MC, Chen CH, Yu JM, et al. A double-blind, placebo-controlled study of naltrexone in the treatment of alcohol dependence in Taiwan. Addict Biol. 2005;10(3):289–92.CrossRefPubMedGoogle Scholar
  44. 44.
    Davidson D, Saha C, Scifres S, et al. Naltrexone and brief counseling to reduce heavy drinking in hazardous drinkers. Addict Behav. 2004;29(6):1253–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Galarza NJ, Díaz Ramírez D, Guzmán F, et al. The use of naltrexone to treat ambulatory patients with alcohol dependence. Bol Asoc Med P R. 1997;89(10–12):157–60.PubMedGoogle Scholar
  46. 46.
    Gastpar M, Bonnet U, Böning J, et al. Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study. J Clin Psychopharmacol. 2002;22(6):592–8.CrossRefPubMedGoogle Scholar
  47. 47.
    Kranzler HR, Wesson DR, Billot L. Naltrexone depot for treatment of alcohol dependence: a multicenter, randomized, placebo-controlled clinical trial. Alcohol Clin Exp Res. 2004;28(7):1051–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Garbutt JC, Kranzler HR, O’malley SS, et al. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617–25.CrossRefPubMedGoogle Scholar
  49. 49.
    Kranzler HR, Modesto-Lowe V, Nuwayser ES. Sustained-release naltrexone for alcoholism treatment: a preliminary study. Alcohol Clin Exp Res. 1998;22(5):1074–9.PubMedGoogle Scholar
  50. 50.
    Krupitsky EM, Zvartau EE, Masalov DV, et al. Naltrexone for heroin dependence treatment in St. Petersburg, Russia. J Subst Abuse Treat. 2004;26(4):285–94.CrossRefPubMedGoogle Scholar
  51. 51.
    National Research Council Committee on Clinical Evaluation of. Narcotic antagonists. Clinical evaluation of naltrexone treatment of opiate-dependent individuals. Arch Gen Psychiatry. 1978;35(3):335–40.CrossRefGoogle Scholar
  52. 52.
    San L, Pomarol G, Peri JM, et al. Follow-up after a six-month maintenance period on naltrexone versus placebo in heroin addicts. Br J Addict. 1991;86(8):983–90.CrossRefPubMedGoogle Scholar
  53. 53.
    Lerner A, Sigal M, Bacalu A, et al. A naltrexone double blind placebo controlled study in Israel. Isr J Psychiatry Relat Sci. 1992;29(1):36–43.PubMedGoogle Scholar
  54. 54.
    Comer SD, Sullivan MA, Yu E, et al. Injectable, sustained-release naltrexone for the treatment of opioid dependence: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2006;63(2):210–8.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence. Lancet. 2011;378(9792):665.CrossRefPubMedGoogle Scholar
  56. 56.
    King A, Cao D, Zhang L, Rueger SY. Effects of the opioid receptor antagonist naltrexone on smoking and related behaviors in smokers preparing to quit: a randomized controlled trial. Addiction. 2013;108(10):1836–44.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    King AC, Cao D, O’Malley SS, et al. Effects of naltrexone on smoking cessation outcomes and weight gain in nicotine-dependent men and women. J Clin Psychopharmacol. 2012;32(5):630–6.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Covey LS, Glassman AH, Stetner F. Naltrexone effects on short-term and long-term smoking cessation. J Addict Dis. 1999;18(1):31–40.CrossRefPubMedGoogle Scholar
  59. 59.
    Wewers ME, Dhatt R, Tejwani GA. Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology (Berl). 1998;140(2):185–90.CrossRefPubMedGoogle Scholar
  60. 60.
    King A, de Wit H, Riley RC, et al. Efficacy of naltrexone in smoking cessation: a preliminary study and an examination of sex differences. Nicotine Tob Res. 2006;8(5):671–82.CrossRefPubMedGoogle Scholar
  61. 61.
    Schmitz JM, Stotts AL, Rhoades HM, Grabowski J. Naltrexone and relapse prevention treatment for cocaine-dependent patients. Addict Behav. 2001;26(2):167–80.CrossRefPubMedGoogle Scholar
  62. 62.
    Jayaram-lindström N, Hammarberg A, Beck O, Franck J. Naltrexone for the treatment of amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry. 2008;165(11):1442–8.CrossRefPubMedGoogle Scholar
  63. 63.
    Kim SW, Grant JE, Adson DE, Shin YC. Double-blind naltrexone and placebo comparison study in the treatment of pathological gambling. Biol Psychiatry. 2001;49(11):914–21.CrossRefPubMedGoogle Scholar
  64. 64.
    Grant JE, Kim SW, Hartman BK. A double-blind, placebo-controlled study of the opiate antagonist naltrexone in the treatment of pathological gambling urges. J Clin Psychiatry. 2008;69(5):783–9.CrossRefPubMedGoogle Scholar
  65. 65.
    Grant JE, Kim SW, Odlaug BL. A double-blind, placebo-controlled study of the opiate antagonist, naltrexone, in the treatment of kleptomania. Biol Psychiatry. 2009;65(7):600–6.CrossRefPubMedGoogle Scholar
  66. 66.
    Grant JE, Odlaug BL, Schreiber LR, Kim SW. The opiate antagonist, naltrexone, in the treatment of trichotillomania: results of a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2014;34(1):134–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Kim SW, Grant JE, Adson DE, Remmel RP. A preliminary report on possible naltrexone and nonsteroidal analgesic interactions. J Clin Psychopharmacol. 2001;21(6):632–4.CrossRefPubMedGoogle Scholar
  68. 68.
    Mitchell JE, Morley JE, Levine AS, Hatsukami D, Gannon M, Pfohl D. High-dose naltrexone therapy and dietary counseling for obesity. Biol Psychiatry. 1987;22(1):35–42.CrossRefPubMedGoogle Scholar
  69. 69.
    Knopman DS, Hartman M. Cognitive effects of high-dose naltrexone in patients with probable Alzheimer’s disease. J Neurol Neurosurg Psychiatr. 1986;49(11):1321–2.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Substance Abuse and Mental Health Service Administration (SAMHSA). Naltrexone. Last updated: 11/10/2015. http://www.samhsa.gov/medication-assisted-treatment/treatment/naltrexone. Last visited 22 Feb 2016.
  71. 71.
    Lucey MR, Silverman BL, Illeperuma A, O’brien CP. Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics. Alcohol Clin Exp Res. 2008;32(3):498–504.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Psychiatry and Behavioral SciencesStanford University School of MedicineStanfordUSA
  2. 2.Gilbert and Rose Marie Chagouri School of MedicineByblosLebanon

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