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Disulfiram: Side Effects and Toxicity

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Disulfiram

Abstract

This chapter is a clinical review of the various common and uncommon side effects of disulfiram when used in patients with alcohol and/or cocaine dependence. Among the side effects noted liver toxicity, neuropathy and psychosis are the most commonly seen. Few aspects of the disulfiram–ethanol reaction and disulfiram-induced catatonia are also discussed. Management and monitoring of side effects when using disulfiram is also elaborated from a clinical point of view.

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References

  1. Chick J. Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Saf. 1999;20(5):427–35.

    Article  PubMed  Google Scholar 

  2. Wright C, Vafier JA, Lake CR. Disulfiram-induced fulminating hepatitis: guidelines for liver-panel monitoring. J Clin Psychiatry. 1988;49(11):430–4.

    PubMed  Google Scholar 

  3. Kalra G, De Sousa A, Shrivastava A. Disulfiram in the management of alcohol dependence: a comprehensive clinical review. Open J Psychiatry. 2014;4(1):43.

    Article  Google Scholar 

  4. Björnsson E, Nordlinder H, Olsson R. Clinical characteristics and prognostic markers in disulfiram-induced liver injury. J Hepatol. 2006;44(4):791–7.

    Article  PubMed  Google Scholar 

  5. Iber FL, Lee K, Lacoursiere R, Fuller R. Liver toxicity encountered in the Veterans Administration trial of disulfiram in alcoholics. Alcohol Clin Exp Res. 1987;11(3):301–4.

    Article  PubMed  Google Scholar 

  6. Forns X, Caballería J, Bruguera M, Salmerón JM, Vilella A, Mas A, Parés A, Rodés J. Disulfiram-induced hepatitis. Report of four cases and review of the literature. J Hepatol. 1994;21(5):853–7.

    Article  PubMed  Google Scholar 

  7. Petersen EN. The pharmacology and toxicology of disulfiram and its metabolites. Acta Psychiatr Scand. 1992;86(S369):7–13.

    Article  Google Scholar 

  8. Eisen HJ, Ginsberg AL. Disulfiram hepatotoxicity. Ann Intern Med. 1975;83(5):673–5.

    Article  PubMed  Google Scholar 

  9. Vazquez JJ, Pardo-Mindan J. Liver cell injury (bodies similar to Lafora’s) in alcoholics treated with disulfiram (Antabuse). Histopathology. 1979;3(5):377–84.

    Article  PubMed  Google Scholar 

  10. Verge C, Lucena MI, López-Torres E, Puche-García MJ, Fraga E, Romero-Gomez M, Andrade RJ. Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs. World J Gastroenterol. 2006;12(31):5078–83.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Filosto M, Tentorio M, Broglio L, Buzio S, Lazzarini C, Pasolini MP, Cotelli MS, Scarpelli M, Mancuso M, Choub A, Padovani A. Disulfiram neuropathy: two cases of distal axonopathy. Clin Toxicol. 2008;46(4):314–6.

    Article  Google Scholar 

  12. Mohapatra S, Sahoo MR, Rath N. Disulfiram-induced neuropathy: a case report. Gen Hosp Psychiatry. 2015;37(1):97–9.

    Article  PubMed  Google Scholar 

  13. Tran AT, Rison RA, Beydoun SR. Disulfiram neuropathy: two case reports. J Med Case Rep. 2016;10(1):72.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Orakzai A, Guerin M, Beatty S. Disulfiram-induced transient optic and peripheral neuropathy: a case report. Ir J Med Sci. 2007;176(4):319–21.

    Article  PubMed  Google Scholar 

  15. Kulkarni RR, Pradeep AV, Bairy BK. Disulfiram-induced combined irreversible anterior ischemic optic neuropathy and reversible peripheral neuropathy: a prospective case report and review of the literature. J Neuropsychiatr Clin Neurosci. 2013;25(4):339–42.

    Article  Google Scholar 

  16. Santos T, Campos AM, Morais H. Sensory-motor axonal polyneuropathy involving cranial nerves: an uncommon manifestation of disulfiram toxicity. Clin Neurol Neurosurg. 2017;152:12–5.

    Article  PubMed  Google Scholar 

  17. Barth KS, Malcolm RJ. Disulfiram: an old therapeutic with new applications. CNS Neurol Disord Drug Targets. 2010;9(1):5–12.

    Article  PubMed  Google Scholar 

  18. De JS, Caparros-Lefebvre D, Nkenjuo JB, Hurtevent JF, Petit H. Acute and reversible myoclonic encephalopathy, extrapyramidal syndrome, polyneuropathy caused by chronic disulfiram poisoning. Rev Neurol. 1995;151(11):667–9.

    Google Scholar 

  19. Mohapatra S, Rath NR. Disulfiram induced psychosis. Clin Psychopharmacol Neurosci. 2017;15(1):68–70.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Melo RC, Lopes R, Alves JC. A case of psychosis in disulfiram treatment for alcoholism. Case Rep Psychiatry. 2014;2014:561092.

    PubMed  PubMed Central  Google Scholar 

  21. Sherif PA, Murthy KK. Psychosis and enuresis during disulfiram therapy. Indian J Psychiatry. 2006;48(1):62–5.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Luykx JJ, Vis R, Tijdink JK, Dirckx M, Van Hecke J, Vinkers CH. Psychotic symptoms after combined metronidazole-disulfiram use. J Clin Psychopharmacol. 2013;33(1):136–7.

    Article  PubMed  Google Scholar 

  23. 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 

  24. Spiegel DR, McCroskey A, Puaa K, Meeker G, Hartman L, Hudson J, Hung YC. A case of disulfiram-induced psychosis in a previously asymptomatic patient maintained on mixed amphetamine salts: a review of the literature and possible pathophysiological explanations. Clin Neuropharmacol. 2016;39(5):272–5.

    Article  PubMed  Google Scholar 

  25. Goswami HK, Bhuyan D, Talukdar B. Catatonia induced by disulfiram. Open J Psychiatry Allied Sci. 2015;6(2):143–5.

    Article  Google Scholar 

  26. Balaban OD, Atagun MI, Alpkan LR. A case of catatonia induced by disulfiram. J Psychiatr Neurol Sci. 2010;23:215–8.

    Google Scholar 

  27. Laplane D, Attal N, Sauron B, de Billy A, Dubois B. Lesions of basal ganglia due to disulfiram neurotoxicity. J Neurol Neurosurg Psychiatry. 1992;55:925–9.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Fuller RK, Gordis E. Does disulfiram have a role in alcoholism treatment today? Addiction. 2004;99(1):21–4.

    Article  PubMed  Google Scholar 

  29. Nayak V, Chogtu B, Virupaksha D, Bhandary PV. Disulfiram induced catatonia. Case Study Case Rep. 2011;1:6–8.

    Google Scholar 

  30. Kulkarni RR, Bairy BK. Disulfiram induced reversible hypertension: a prospective case study and brief review. Indian J Psychol Med. 2010;35(4):217–9.

    Google Scholar 

  31. Rogers WK, Benowitz NL, Wilson KM, Abbott JA. Effect of disulfiram on adrenergic function. Clin Pharmacol Ther. 1979;25(4):469–75.

    Article  PubMed  Google Scholar 

  32. Grover S, Mattoo SK, Pendharkar S, Kandappan V. Sexual dysfunction in patients with alcohol and opioid dependence. Indian J Psychol Med. 2014;36(4):355–65.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jensen SB. Sexual function and dysfunction in younger married alcoholics: a comparative study. Acta Psychiatr Scand. 1984;69(6):543–9.

    Article  PubMed  Google Scholar 

  34. Daniel DG, Swallows A, Wolff F. Capgras delusion and seizures in association with therapeutic dosages of disulfiram. South Med J. 1987;80(12):1577–9.

    Article  PubMed  Google Scholar 

  35. Tartara E, Fanucchi S, D’Errico I, Farina LM, Casoni F, Sinforiani E, Micieli G, Costa A. A case of Wernicke encephalopathy combined with disulfiram intoxication. Cogn Behav Neurol. 2013;26(2):93–8.

    Article  PubMed  Google Scholar 

  36. Borrett D, Ashby P, Bilbao J, Carlen P. Reversible, late-onset disulfiram-induced neuropathy and encephalopathy. Ann Neurol. 1985;17(4):396–9.

    Article  PubMed  Google Scholar 

  37. Krauss JK, Mohadjer M, Wakhloo AK, Mundinger F. Dystonia and akinesia due to pallidoputaminal lesions after disulfiram intoxication. Mov Disord. 1991;6(2):166–70.

    Article  PubMed  Google Scholar 

  38. Rae C, Tesson M, Babich JW, Boyd M, Sorensen A, Mairs RJ. The role of copper in disulfiram-induced toxicity and radiosensitization of cancer cells. J Nucl Med. 2013;54(6):953–60.

    Article  PubMed  Google Scholar 

  39. Haley TJ. Disulfiram (tetraethylthioperoxydicarbonic diamide): a reappraisal of its toxicity and therapeutic application. Drug Metab Rev. 1979;9(2):319–35.

    Article  PubMed  Google Scholar 

  40. Zorzon M, Masè G, Biasutti E, Vitrani B, Cazzato G. Acute encephalopathy and polyneuropathy after disulfiram intoxication. Alcohol Alcohol. 1995;30(5):629–31.

    PubMed  Google Scholar 

  41. Fletcher K, Stone E, Mohamad MW, Faulder GC, Faulder RM, Jones K, Morgan D, Wegerdt J, Kelly M, Chick J. A breath test to assess compliance with disulfiram. Addiction. 2006;101(12):1705–10.

    Article  PubMed  Google Scholar 

  42. Kitson TM. The disulfiram-ethanol reaction: a review. J Stud Alcohol. 1977;38(1):96–113.

    Article  PubMed  Google Scholar 

  43. Fuller RK, Branchey L, Brightwell DR, Derman RM, Emrick CD, Iber FL, James KE, Lacoursiere RB, Lee KK, Lowenstam I, Maany I. Disulfiram treatment of alcoholism: a Veterans Administration cooperative study. JAMA. 1986;256(11):1449–55.

    Article  PubMed  Google Scholar 

  44. Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother. 2000;34(2):255–7.

    Article  PubMed  Google Scholar 

  45. Karamanakos PN, Pappas P, Boumba VA, Thomas C, Malamas M, Vougiouklakis T, Marselos M. Pharmaceutical agents known to produce disulfiram-like reaction: effects on hepatic ethanol metabolism and brain monoamines. Int J Toxicol. 2007;26(5):423–32.

    Article  PubMed  Google Scholar 

  46. 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 

  47. Mutschler J, Grosshans M, Koopmann A, Mann K, Kiefer F, Hermann D. Urinary ethylglucuronide assessment in patients treated with disulfiram: a tool to improve verification of abstention and safety. Clin Neuropharmacol. 2010;33(6):285–7.

    Article  PubMed  Google Scholar 

  48. Bourcier S, Mongardon N, Daviaud F, Moachon L, Arnould MA, Perruche F, Pène F, Cariou A. Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock. Am J Emerg Med. 2013;31(1):270–1.

    Article  PubMed  Google Scholar 

  49. Lindros KO, Stowell A, Pikkarainen P, Salaspuro M. The disulfiram (Antabuse)-alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res. 1981;5(4):528–30.

    Article  PubMed  Google Scholar 

  50. Sande M, Thompson D, Monte AA. Fomepizole for severe disulfiram-ethanol reactions. Am J Emerg Med. 2012;30(1):262–e3.

    Article  PubMed  Google Scholar 

  51. Ren S, Cao Y, Zhang X, Jiao S, Qian S, Liu P. Cephalosporin induced disulfiram-like reaction: a retrospective review of 78 cases. Int Surg. 2014;99(2):142–6.

    Article  PubMed  PubMed Central  Google Scholar 

  52. O’Shea B. Disulfiram revisited. Hosp Med. 2000;61(12):849–51.

    Article  PubMed  Google Scholar 

  53. Altun G, Altun A, Erdogan O. Acute myocardial infarction due to disulfiram (antabus)–alcohol interaction. Cardiovasc Drugs Ther. 2006;20(5):391–2.

    Article  PubMed  Google Scholar 

  54. Rothrock JF, Johnson PC, Rothrock SM, Merkley R. Fulminant polyneuritis after overdose of disulfiram and ethanol. Neurology. 1984;34(3):357–60.

    Article  PubMed  Google Scholar 

  55. Stransky G, Lambing MK, Simmons GT, Robinson A. Methemoglobinemia in a fatal case of disulfiram-ethanol reaction. J Anal Toxicol. 1997;21(2):178–9.

    Article  PubMed  Google Scholar 

  56. Fernandez D. Another esophageal rupture after alcohol and disulfiram. N Engl J Med. 1972;286(11):610–2.

    PubMed  Google Scholar 

  57. Banys P. The clinical use of disulfiram (Antabuse®): a review. J Psychoactive Drugs. 1988;20(3):243–61.

    Article  PubMed  Google Scholar 

  58. Poulsen HE, Loft S, Andersen JR, Andersen M. Disulfiram therapy–adverse drug reactions and interactions. Acta Psychiatr Scand. 1992;86(S369):59–66.

    Article  Google Scholar 

  59. Brewer C. Recent developments in disulfiram treatment. Alcohol Alcohol. 1993;28(4):383–95.

    PubMed  Google Scholar 

  60. Haddock NF, Wilkin JK. Cutaneous reactions to lower aliphatic alcohols before and during disulfiram therapy. Arch Dermatol. 1982;118(3):157–9.

    Article  PubMed  Google Scholar 

  61. Palatty PL, Saldanha E. Status of disulfiram in present day alcoholic deaddiction therapy. Indian J Psychiatry. 2011;53(1):25–9.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Brewer C, Hardt F. Preventing disulfiram hepatitis in alcohol abusers: inappropriate guidelines and the significance of nickel allergy. Addict Biol. 1999;4(3):303–8.

    Article  PubMed  Google Scholar 

  63. Brewer C, Streel E, Skinner M. Supervised disulfiram’s superior effectiveness in alcoholism treatment: ethical, methodological, and psychological aspects. Alcohol Alcohol. 2017;1:1–7.

    Google Scholar 

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De Sousa, A. (2019). Disulfiram: Side Effects and Toxicity. In: Disulfiram. Springer, Singapore. https://doi.org/10.1007/978-981-32-9876-7_7

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