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Disulfiram in the Management of Cocaine Dependence and Other Psychiatric Disorders

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Disulfiram

Abstract

This chapter provides an in-depth discussion on the rationale and efficacy of the use of disulfiram in cocaine dependence and pathological gambling. Various hypothetical mechanisms of action of the drug, proven scientific facts and studies of the use of disulfiram in these populations are discussed. This is combined with an analysis of the position of disulfiram in the management of these disorders.

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References

  1. Calabria B, Degenhardt L, Briegleb C, Vos T, Hall W, Lynskey M, Callaghan B, Rana U, McLaren J. Systematic review of prospective studies investigating remission from amphetamine, cannabis, cocaine or opioid dependence. Addict Behav. 2010;35(8):741–9.

    Article  PubMed  Google Scholar 

  2. Chen CY, Anthony JC. Epidemiological estimates of risk in the process of becoming dependent upon cocaine: cocaine hydrochloride powder versus crack cocaine. Psychopharmacology. 2004;172(1):78–86.

    Article  PubMed  Google Scholar 

  3. Lima MS, Soares BG, Reisser AA, Farrell M. Pharmacological treatment of cocaine dependence: a systematic review. Addiction. 2002;97(8):931–49.

    Article  PubMed  Google Scholar 

  4. Karila L, Gorelick D, Weinstein A, Noble F, Benyamina A, Coscas S, Blecha L, Lowenstein W, Martinot JL, Reynaud M, Lépine JP. New treatments for cocaine dependence: a focused review. Int J Neuropsychopharmacol. 2008;11(3):425–38.

    Article  PubMed  Google Scholar 

  5. Dackis CA, Gold MS. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev. 1985;9(3):469–77.

    Article  PubMed  Google Scholar 

  6. Schroeder JP, Cooper DA, Schank JR, Lyle MA, Gaval-Cruz M, Ogbonmwan YE, Pozdeyev N, Freeman KG, Iuvone PM, Edwards GL, Holmes PV. Disulfiram attenuates drug-primed reinstatement of cocaine seeking via inhibition of dopamine β-hydroxylase. Neuropsychopharmacology. 2010;35(12):2440–6.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kosten TR, Wu G, Huang W, Harding MJ, Hamon SC, Lappalainen J, Nielsen DA. Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylase. Biol Psychiatry. 2013;73(3):219–24.

    Article  PubMed  Google Scholar 

  8. Gaval-Cruz M, Schroeder JP, Liles LC, Javors MA, Weinshenker D. Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced seizures. Pharmacol Biochem Behav. 2008;89(4):556–62.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Suh JJ, Pettinati HM, Kampman KM, O’Brien CP. The status of disulfiram: a half of a century later. J Clin Psychopharmacol. 2006;26(3):290–302.

    Article  PubMed  Google Scholar 

  10. Savas MC, Güllü İH. Disulfiram–ethanol test reaction: significance of supervision. Ann Pharmacother. 1997;31(3):374–5.

    Article  PubMed  Google Scholar 

  11. Krampe H, Ehrenreich H. Supervised disulfiram as adjunct to psychotherapy in alcoholism treatment. Curr Pharm Des. 2010;16(19):2076–90.

    Article  PubMed  Google Scholar 

  12. Savolainen K, Hervonen H, Lehto VP, Mattila MJ. Neurotoxic effects of disulfiram on autonomic nervous system in rat. Acta Pharmacol Toxicol. 1984;55(5):339–44.

    Article  Google Scholar 

  13. McCance-Katz EF, Kosten TR, Jatlow P. Chronic disulfiram treatment effects on intranasal cocaine administration: initial results. Biol Psychiatry. 1998;43(7):540–3.

    Article  PubMed  Google Scholar 

  14. Devoto P, Flore G, Saba P, Cadeddu R, Gessa GL. Disulfiram stimulates dopamine release from noradrenergic terminals and potentiates cocaine-induced dopamine release in the prefrontal cortex. Psychopharmacology. 2012;219(4):1153–64.

    Article  PubMed  Google Scholar 

  15. Beck O, Helander A, Carlsson S, Borg S. Changes in serotonin metabolism during treatment with the aldehyde dehydrogenase inhibitors disulfiram and cyanamide. Pharmacol Toxicol. 1995;77(5):323–6.

    Article  PubMed  Google Scholar 

  16. Noble EP. Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review. Eur Psychiatry. 2000;15(2):79–89.

    Article  PubMed  Google Scholar 

  17. Groman SM, James AS, Jentsch JD. Poor response inhibition: at the nexus between substance abuse and attention deficit/hyperactivity disorder. Neurosci Biobehav Rev. 2009;33(5):690–8.

    Article  PubMed  Google Scholar 

  18. Kalivas PW. Neurobiology of cocaine addiction: implications for new pharmacotherapy. Am J Addict. 2007;16(2):71–8.

    Article  PubMed  Google Scholar 

  19. Hameedi FA, Rosen MI, McCance-Katz EF, McMahon TJ, Price LH, Jatlow PI, Woods SW, Kosten TR. Behavioral, physiological, and pharmacological interaction of cocaine and disulfiram in humans. Biol Psychiatry. 1995;37(8):560–3.

    Article  PubMed  Google Scholar 

  20. Mooney M, Sofuoglu M, Dudish-Poulsen S, Hatsukami DK. Preliminary observations of paranoia in a human laboratory study of cocaine. Addict Behav. 2006;31(7):1245–51.

    Article  PubMed  Google Scholar 

  21. Gaval-Cruz M, Weinshenker D. Mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009;9(4):175–87.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Penberthy JK, Ait-Daoud N, Vaughan M, Fanning T. Review of treatment for cocaine dependence. Curr Drug Abuse Rev. 2010;3(1):49–62.

    Article  PubMed  Google Scholar 

  23. Vocci FJ, Elkashef A. Pharmacotherapy and other treatments for cocaine abuse and dependence. Curr Opin Psychiatry. 2005;18(3):265–70.

    Article  PubMed  Google Scholar 

  24. Shorter D, Domingo CB, Kosten TR. Emerging drugs for the treatment of cocaine use disorder: a review of neurobiological targets and pharmacotherapy. Expert Opin Emerg Drugs. 2015;20(1):15–29.

    Article  PubMed  Google Scholar 

  25. Magura S, Rosenblum A. Modulating effect of alcohol use on cocaine use. Addict Behav. 2000;25(1):117–22.

    Article  PubMed  Google Scholar 

  26. Grassi MC, Cioce AM, Dei Giudici F, Antonilli L, Nencini P. Short-term efficacy of disulfiram or naltrexone in reducing positive urinalysis for both cocaine and cocaethylene in cocaine abusers: a pilot study. Pharmacol Res. 2007;55(2):117–21.

    Article  PubMed  Google Scholar 

  27. Gossop M, Carroll KM. Disulfiram cocaine and alcohol: two outcomes for the price of one? Alcohol Alcohol. 2006;41(2):119–20.

    Article  PubMed  Google Scholar 

  28. Carroll KM, Nich C, Ball SA, McCance E, Rounsavile BJ. Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction. 1998;93(5):713–27.

    Article  PubMed  Google Scholar 

  29. Carroll KM, Fenton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial. Arch Gen Psychiatry. 2004;61(3):264–72.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Petrakis IL, Carroll KM, Nich C, Gordon LT, McCance-Katz EF, Frankforter T, Rounsaville BJ. Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. Addiction. 2000;95(2):219–28.

    Article  PubMed  Google Scholar 

  31. Carroll KM, Nich C, Ball SA, McCance E, Frankforter TL, Rounsaville BJ. One-year follow-up of disulfiram and psychotherapy for cocaine-alcohol users: sustained effects of treatment. Addiction. 2000;95(9):1335–49.

    Article  PubMed  Google Scholar 

  32. George TP, Chawarski MC, Pakes J, Carroll KM, Kosten TR, Schottenfeld RS. Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial. Biol Psychiatry. 2000;47(12):1080–6.

    Article  PubMed  Google Scholar 

  33. Oliveto A, Poling J, Mancino MJ, Feldman Z, Cubells JF, Pruzinsky R, Gonsai K, Cargile C, Sofuoglu M, Chopra MP, Gonzalez-Haddad G. Randomized, double blind, placebo-controlled trial of disulfiram for the treatment of cocaine dependence in methadone-stabilized patients. Drug Alcohol Depend. 2011;113(2–3):184–91.

    Article  PubMed  Google Scholar 

  34. Carroll K, Ziedonis D, O’Malley S, McCance-Katz E, Gordon L, Rounsaville B. Pharmacologic interventions for alcohol-and cocaine-abusing individuals: a pilot study of disulfiram vs. naltrexone. Am J Addict. 1993;2(1):77–9.

    Article  Google Scholar 

  35. Pettinati HM, Kampman KM, Lynch KG, Xie H, Dackis C, Rabinowitz AR, Charles PO. A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. Addict Behav. 2008;33(5):651–67.

    Article  PubMed  Google Scholar 

  36. Nich C, McCance-Katz EF, Petrakis IL, Cubells JF, Rounsaville BJ, Carroll KM. Sex differences in cocaine-dependent individuals’ response to disulfiram treatment. Addict Behav. 2004;29(6):1123–8.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Higgins ST, Budney AJ, Bickel WK, Hughes JR, Foerg F. Disulfiram therapy in patients abusing cocaine and alcohol. Am J Psychiatry. 1993;150(4):675–6.

    PubMed  Google Scholar 

  38. Baker JR, Jatlow P, McCance-Katz EF. Disulfiram effects on responses to intravenous cocaine administration. Drug Alcohol Depend. 2007;87(2–3):202–9.

    Article  PubMed  Google Scholar 

  39. Carroll KM, Nich C, Shi JM, Eagan D, Ball SA. Efficacy of disulfiram and twelve step facilitation in cocaine-dependent individuals maintained on methadone: a randomized placebo-controlled trial. Drug Alcohol Depend. 2012;126(1–2):224–31.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Carroll KM, Nich C, Petry NM, Eagan DA, Shi JM, Ball SA. A randomized factorial trial of disulfiram and contingency management to enhance cognitive behavioral therapy for cocaine dependence. Drug Alcohol Depend. 2016;160:135–42.

    Article  PubMed  PubMed Central  Google Scholar 

  41. DeVito EE, Babuscio TA, Nich C, Ball SA, Carroll KM. Gender differences in clinical outcomes for cocaine dependence: randomized clinical trials of behavioral therapy and disulfiram. Drug Alcohol Depend. 2014;145:156–67.

    Article  PubMed  Google Scholar 

  42. Jofre-Bonet M, Sindelar JL, Petrakis IL, Nich C, Frankforter T, Rounsaville BJ, Carroll KM. Cost effectiveness of disulfiram: treating cocaine use in methadone-maintained patients. J Subst Abuse Treat. 2004;26(3):225–32.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Haile CN, De La Garza R II, Mahoney JJ III, Nielsen DA, Kosten TR, Newton TF. The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial. PLoS One. 2012;7(11):e47702.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Pani PP, Trogu E, Vacca R, Amato L, Vecchi S, Davoli M. Disulfiram for the treatment of cocaine dependence. Cochrane Database Syst Rev 2010;(1);CD007024.

    Google Scholar 

  45. Kalayasiri R, Sughondhabirom A, Gueorguieva R, Coric V, Lynch WJ, Morgan PT, Cubells JF, Malison RT. Self-reported paranoia during laboratory binge cocaine self-administration in humans. Pharmacol Biochem Behav. 2006;83(2):249–56.

    Article  PubMed  Google Scholar 

  46. Malcolm R, Olive MF, Lechner W. The safety of disulfiram for the treatment of alcohol and cocaine dependence in randomized clinical trials: guidance for clinical practice. Expert Opin Drug Saf. 2008;7(4):459–72.

    Article  PubMed  Google Scholar 

  47. Roache JD, Kahn R, Newton TF, Wallace CL, Murff WL, De La Garza R II, Rivera O, Anderson A, Mojsiak J, Elkashef A. A double-blind, placebo-controlled assessment of the safety of potential interactions between intravenous cocaine, ethanol, and oral disulfiram. Drug Alcohol Depend. 2011;119(1–2):37–45.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Haile CN, During MJ, Jatlow PI, Kosten TR, Kosten TA. Disulfiram facilitates the development and expression of locomotor sensitization to cocaine in rats. Biol Psychiatry. 2003;54(9):915–21.

    Article  PubMed  Google Scholar 

  49. Nagendra SN, Faiman MD, Davis K, Wu JY, Newby X, Schloss JV. Carbamoylation of brain glutamate receptors by a disulfiram metabolite. J Biol Chem. 1997;272(39):24247–51.

    Article  PubMed  Google Scholar 

  50. Kalivas PW, Volkow ND. New medications for drug addiction hiding in glutamatergic neuroplasticity. Mol Psychiatry. 2011;16(10):974–86.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Kalivas PW. The glutamate homeostasis hypothesis of addiction. Nat Rev Neurosci. 2009;10(8):561–72.

    Article  PubMed  Google Scholar 

  52. Raylu N, Oei TP. Pathological gambling: a comprehensive review. Clin Psychol Rev. 2002;22(7):1009–61.

    Article  PubMed  Google Scholar 

  53. Hall GW, Carriero NJ, Takushi RY, Montoya ID, Preston KL, Gorelick DA. Pathological gambling among cocaine-dependent outpatients. Am J Psychiatry. 2000;157(7):1127–33.

    Article  PubMed  Google Scholar 

  54. American Psychiatric Association. Diagnostic and statistical manual for the classification of psychiatric disorders – 5th edition (DSM-5). Philadelphia: American Psychiatric Publishing; 2013.

    Google Scholar 

  55. Potenza MN. The neurobiology of pathological gambling and drug addiction: an overview and new findings. Philos Trans R Soc Lond B Biol Sci. 2008;363(1507):3181–9.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Goudriaan AE, Oosterlaan J, de Beurs E, Van den Brink W. Pathological gambling: a comprehensive review of biobehavioral findings. Neurosci Biobehav Rev. 2004;28(2):123–41.

    Article  PubMed  Google Scholar 

  57. Reuter J, Raedler T, Rose M, Hand I, Gläscher J, Büchel C. Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci. 2005;8(2):147–66.

    Article  PubMed  Google Scholar 

  58. Meyer G, Schwertfeger J, Exton MS, Janssen OE, Knapp W, Stadler MA, Schedlowski M, Krüger TH. Neuroendocrine response to casino gambling in problem gamblers. Psychoneuroendocrinology. 2004;29(10):1272–80.

    Article  PubMed  Google Scholar 

  59. Bergh C, Eklund T, Södersten P, Nordin C. Altered dopamine function in pathological gambling. Psychol Med. 1997;27(2):473–5.

    Article  PubMed  Google Scholar 

  60. Potenza MN, Steinberg MA, Skudlarski P, Fulbright RK, Lacadie CM, Wilber MK, Rounsaville BJ, Gore JC, Wexler BE. Gambling urges in pathological gambling: a functional magnetic resonance imaging study. Arch Gen Psychiatry. 2003;60(8):828–36.

    Article  PubMed  Google Scholar 

  61. Kim SW, Grant JE. An open naltrexone treatment study in pathological gambling disorder. Int Clin Psychopharmacol. 2001;16(5):285–9.

    Article  PubMed  Google Scholar 

  62. Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry. 2007;62(6):652–7.

    Article  PubMed  Google Scholar 

  63. Hollander E, Sood E, Pallanti S, Baldini-Rossi N, Baker B. Pharmacological treatments of pathological gambling. J Gambl Stud. 2005;21(1):99–108.

    Article  PubMed  Google Scholar 

  64. Kim SW, Grant JE, Eckert ED, Faris PL, Hartman BK. Pathological gambling and mood disorders: clinical associations and treatment implications. J Affect Disord. 2006;92(1):109–16.

    Article  PubMed  Google Scholar 

  65. Mutschler J, Grosshans M, Bühler M, Diehl A, Kiefer F. Disulfiram in the treatment of pathological gambling? Pharmacopsychiatry. 2009;42(5):110.

    Google Scholar 

  66. Mutschler J, Bühler M, Diehl A, Mann K, Kiefer F. Disulfiram, an old drug with new potential in the treatment of pathological gambling? Med Hypotheses. 2010;74(1):209–10.

    Article  PubMed  Google Scholar 

  67. Mutschler J, Bühler M, Grosshans M, Diehl A, Mann K, Kiefer F. Disulfiram, an option for the treatment of pathological gambling? Alcohol Alcohol. 2010;45(2):214–6.

    Article  PubMed  Google Scholar 

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De Sousa, A. (2019). Disulfiram in the Management of Cocaine Dependence and Other Psychiatric Disorders. In: Disulfiram. Springer, Singapore. https://doi.org/10.1007/978-981-32-9876-7_4

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