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Naltrexone: A Pan-Addiction Treatment?

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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.

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References

  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. 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. European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/003687/WC500185583.pdf. Last visited 4 Jun 2016.

  4. Therapeutic Goods Administration. https://search.tga.gov.au/s/search.html?collection=tga-websites-web&query=naltrexone. Last visited 4 Jun 2016.

  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.

    Article  CAS  PubMed  Google Scholar 

  6. Unterwald EM. Naltrexone in the treatment of alcohol dependence. J Addict Med. 2008;2(3):121–7.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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. Food and Drug Administration. Vivitrol drug insert. http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021897s020s023lbl.pdf. Last visited 25 Feb 2016.

  12. Gastfriend DR. Intramuscular extended-release naltrexone: current evidence. Ann N Y Acad Sci. 2011;1216:144–66.

    Article  CAS  PubMed  Google Scholar 

  13. Potenza MN. Should addictive disorders include non-substance-related conditions? Addiction. 2006;101(Suppl):142–51.

    Article  PubMed  Google Scholar 

  14. Petry NM. Should the scope of addictive behaviors be broadened to include pathological gambling? Addiction. 2006;101(S1):152–60.

    Article  PubMed  Google Scholar 

  15. Blanco C, Moreyra P, Nunes EV, et al. Pathological gambling: addiction or obsession? Semin Clin Neuropsychiatry. 2001;6:167–76.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  17. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1987.

    Google Scholar 

  18. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.

    Google Scholar 

  19. Aboujaoude E. Problematic Internet use: an overview. World Psychiatry. 2010;9(2):85–90.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Aboujaoude E. Compulsive buying disorder: a review and update. Curr Pharm Des. 2014;20(25):4021–5.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

  27. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.

    Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  30. Kranzler HR, Tennen H, Armeli S, et al. Targeted naltrexone for problem drinkers. J Clin Psychopharmacol. 2009;29(4):350–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    PubMed  Google Scholar 

  33. Kranzler HR, Armeli S, Tennen H, et al. Targeted naltrexone for early problem drinkers. J Clin Psychopharmacol. 2003;23(3):294–304.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  41. Knox PC, Donovan DM. Using naltrexone in inpatient alcoholism treatment. J Psychoactive Drugs. 1999;31(4):373–88.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  59. Wewers ME, Dhatt R, Tejwani GA. Naltrexone administration affects ad libitum smoking behavior. Psychopharmacology (Berl). 1998;140(2):185–90.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Elias Aboujaoude

  2. Gilbert and Rose Marie Chagouri School of Medicine, Byblos, Lebanon

    Wael O. Salame

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  1. Elias Aboujaoude
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  2. Wael O. Salame
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Correspondence to Elias Aboujaoude.

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Aboujaoude, E., Salame, W.O. Naltrexone: A Pan-Addiction Treatment?. CNS Drugs 30, 719–733 (2016). https://doi.org/10.1007/s40263-016-0373-0

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