Disulfiram in the management of alcohol dependence: A comprehensive clinical review


Disulfiram remains a viable option as a treatment for alcohol dependence and has been shown in recent studies to be successful in treating patients with alcohol dependence in a manner that is superior to both naltrexone and acamprosate. It is also useful in dual diagnosis patients and those with co-morbid cocaine and alcohol dependence. Although disulfiram’s mechanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies have uncovered potential anticraving effects as well. Recent reviews exhort to the importance of supervised disulfiram therapy in highlighting many of the potential and unique benefits of disulfiram. The present article will review the major clinical trials of disulfiram spanning nearly 60 years. It also discusses the usage of disulfiram across diverse populations along with monitoring for compliance and various adverse effects that may be encountered. The paper also reviews certain studies on long acting disulfiram therapy, recent comparative trials of disulfiram and its use in alcohol dependence. The review concludes with the role of disulfiram in the present day and long-term pharmacotherapy of alcohol dependence along with future research needs in this area.

Share and Cite:

Kalra, G. , Sousa, A. and Shrivastava, A. (2014) Disulfiram in the management of alcohol dependence: A comprehensive clinical review. Open Journal of Psychiatry, 4, 43-52. doi: 10.4236/ojpsych.2014.41007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Petrakis, I.L., Nich, C. and Ralevski, E. (2006) Psychotic spectrum disorders and alcohol abuse: A review of pharmacotherapeutic strategies and a report on the effectiveness of naltrexone and disulfiram. Schizophrenia Bulletin, 32, 644-654. http://dx.doi.org/10.1093/schbul/sbl010
[2] De Sousa, A. (2010) The pharmacotherapy of alcohol dependence: A state of the art review. Mens Sana Monographs, 8, 69-82. http://dx.doi.org/10.4103/0973-1229.58820
[3] Deitrich, R.A., Petersen, D. and Vasiliou, V. (2007) Removal of acetaldehyde from the body. Novartis Foundation Symposia, 285, 23-40.
[4] Johansson, B. (1992) A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites. Acta Psychiatrica Scandanavica, 362, 15-26. http://dx.doi.org/10.1111/j.1600-0447. 1992.tb03310.x
[5] Pike, M.G., Mays, D.C., Macomber, D.W. and Lipsky, J.J. (2001) Metabolism of a disulfiram metabolite S-methyl N,N-diethyldithiocarbamate by flavinmonooxygenase in human renal microsomes. Drug Metabolism & Disposition, 29, 127-132.
[6] Larsen, V. (1948) The effects on experimental animals of antabuse (tetraethylthiuram disulfide) in combination with alcohol. Acta Pharmacologica Toxicology, 4, 321-332. http://dx.doi.org/10. 1111/j.1600-0773.1948.tb03354.x
[7] Krampe, H. and Ehrenreich, H. (2010) Supervised disulfiram as adjunct to psychotherapy in alcoholism treatment. Current Pharmaceutical Design, 16, 2076-2090. http://dx.doi.org/10. 2174/138161210791516431
[8] Fuller, R.K. and Gordis, E. (2004) Does disulfiram have a role in alcoholism treatment today? Addiction, 99, 21-24. http://dx.doi.org/10.1111/j.1360-0443.2004.00597.x
[9] Vaccari, A., Saba, P.L., Ruiu, S., Collu, M. and Devoto, P. (1996) Disulfiram and diethyldithiocarbamate intoxication affects the storage and release of striatal dopamine. Toxicology & Applied Pharmacology, 139, 102-108. http://dx.doi.org/10.1006/taap.1996.0147
[10] Muller, C.A. and Banas, R. (2011) Disulfiram: An anticraving substance? American Journal of Psychiatry, 168, 98. http://dx.doi.org/10.1176/appi.ajp.2010.10070943
[11] Johnson, B.A. (2010) Disulfiram. In: Stolerman, I.P., Ed., Encyclopedia of Psychopharmacology. Illustrated Edition, Heidelberg, Springer, 413.
[12] Brewer, C. (2005) Supervised disulfiram is more effective in alcoholics than naltrexone or acamprosate or even psychotherapy: How it works and why it matters. Adicciones, 17, 285-296.
[13] Barth, K.S. and Malcolm, R.J. (2010) Disulfiram: An old therapeutic with new applications. CNS Neurological Disorders & Drug Targets, 9, 5-12. http://dx.doi.org/10.2174/187152710790966678
[14] Krampe, H., Spies, C.D. and Ehrenreich, H. (2011) Superviseddisulfiram in the treatment of alcohol use disorder: A commentary. Alcoholism Clinical & Experimental Research, 35, 1732-1736. http://dx.doi.org/10.1111/j.1530-0277.2011.01519.x
[15] Garbutt, J.C. (2009) The state of pharmacotherapy for the treatment of alcohol dependence. Journal of Substance Abuse Treatment, 36, S15-S23.
[16] Soyka, M., Kranzler, H. and Berglund, M. (2008) World federation of societies of biological psychiatry (WFSBP) guidelines for biological treatment of substance use and related disorders, part 1: Alcoholism. World Journal of Biological Psychiatry, 9, 6-23. http://dx.doi.org/10.1080/15622970 801896390
[17] Ulrichsen, J., Nielsen, M.K. and Ulrichsen, M. (2010) Disulfiram in severe alcoholism—An open controlled study. Nordic Journal of Psychiatry, 64, 356-362. http://dx.doi.org/10.3109/080394810 03686180
[18] Fuller, R.K., Branchey, L., Brightwell, D.R. and The Veterans Study Group (1986) Disulfiram treatment of alcoholism: A Veterans Administration cooperative study. JAMA, 256, 1449-1455.
[19] B?rup, C., Kaiser, A. and Jensen, E. (1992) Long-term Antabuse treatment: Tolerance and reasons for withdrawal. ActaPsychiatricaScandanavica, 86, 47-49.
[20] Liskow, B., Nickel, E.J., Tunley, N., Powell, B.J. and Penick, E.C. (1990) Alcoholics’ attitudes toward and experiences with disulfiram. American Journal of Drug and Alcohol Abuse, 16, 147-160. http://dx.doi.org/10.3109/00952999009001579
[21] Duckert, F. and Johnsen, J. (1987) Behavioral use of disulfiram in the treatment of problem drinking. International Journal of Addiction, 22, 445-454.
[22] O’Farrell, T.J. and Bayog, R.D. (1986) Antabuse contracts for married alcoholics and their spouses: A method to maintain antabuse ingestion and decrease conflict about drinking. Journal of Substance Abuse Treatment, 3, 1-8. http://dx.doi.org/10.1016/0740-5472(86)90002-4
[23] Mutschler, J., Dirican, G. and Funke, S. (2011) Experienced acetaldehyde reaction does not improve treatment response in outpatients treated with supervised disulfiram. Clinical Neuropharmacology, 34, 161-165. http://dx.doi.org/10.1097/WNF.0b013e3182216fd5
[24] Krampe, H., Stawicki, S., Wagner, T., Bartels, C., Aust, C., Ruther, E., Poser, W. and Ehrenreich, H. (2006) Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: Impact of alcohol deterrants on outcome. Alcoholism Clinical and Experimental Research, 30, 86-95. http://dx.doi.org/10.1111/j.1530-0277.2006.00013.x
[25] Krampe, H., Stawicki, S., Hoehe, M.R. and Ehrenreich, H. (2007) Outpatient Long-term Intensive Therapy for Alcoholics (OLITA): A successful biopsychosocial approach to the treatment of alcoholism. Dialogues in Clinical Neuroscience, 9, 399-412.
[26] Kristenson, H. (1992) Long-term antabuse treatment of alcohol-dependent patients. Acta Psychiatrica Scandanavica, 369, 41-45. http://dx.doi.org/10.1111/j.1600-0447.1992.tb03314.x
[27] Mutschler, J., Dirican, G., Gutzeit, A. and Grosshans, M. (2011) Safety and efficacy of long-term disulfiram aftercare. Clinical Neuropharmacology, 34, 195-198. http://dx.doi.org/10.1097/WNF. 0b013e3182285e2d
[28] Brewer, C. (1992) Controlled trials of antabuse in alcoholism: the importance of supervision and adequate dosage. Acta Psychiatrica Scandanavica, 369, 51-58. http://dx.doi.org/10.1111/j.1600-0447.1992.tb03316.x
[29] Kristenson, H. (1995) How to get the best out of antabuse. Alcohol & Alcoholism, 30, 775-783.
[30] Mueser, K.T., Noordsy, D.L., Fox. L. and Wolfe, R. (2003) Disulfiram treatment for alcoholism in severe mental illness. American Journal on Addiction, 12, 242-252.
[31] Milne, H.J. and Parke, T.R. (2007) Hypotension and ST depression as a result of disulfiram ethanol reaction. European Journal of Emergency Medicine, 14, 228-229. http://dx.doi.org/10.1097/MEJ. 0b013e3280bef8a7
[32] Fletcher, K., Stone. E., Mohamad. M.W. and Chick, J. (2006) A breath test to assess compliance with disulfiram. Addiction, 101, 1705-1710. http://dx.doi.org/10.1111/j.1360-0443.2006.01602.x
[33] Regier, D.A., Farmer, M.E. and Rae, D.S. (1990) Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiological Catchment Area (ECA) study. JAMA, 264, 2511-2518. http://dx.doi.org/10.1001/jama.1990.03450190043026
[34] Dixon, L. (1999) Dual diagnosis of substance abuse in schizophrenia: Prevalence and impact on outcomes. Schizophrenia Research, 35, S93-S100. http://dx.doi.org/10.1016/S0920-9964(98)00161-3
[35] Larson, E.W., Olincy, A., Rummans, T.A. and Morse, R.M. (1992) Disulfiram treatment of patients with both alcohol dependence and other psychiatric disorders: A review. Alcoholism Clinical and Experimental Research, 16, 125-130. http://dx.doi.org/10.1111/j.1530-0277.1992.tb00648.x
[36] Guild, J. and Epstein, N.B. (1951) Psychosis during the treatment of alcoholism with tetraethylthiuram disulfide. Quarterly Journal of Studies on Alcohol, 12, 360-365.
[37] Mueser, K.T. and Gingerich, S. (2013) Treating co-occuring psychosis and substance use disorders. Social Work & Public Health, 28, 424-439. http://dx.doi.org/10.1080/19371918.2013.774676
[38] Petrakis, I., Ralevski, E., Nich, C., Levinson, C., Caroll, K., Polling, J., Rounsaville, B. and VA VISN MIRECC Study Group (2007) Naltrexone and disulfiram in patients with alcohol dependence and current depression. Journal of Clinical Psychopharmacology, 27, 160-165. http://dx.doi.org/10. 1097/jcp.0b13e3180337fcb
[39] Ralevski, E., Ball, S., Nich, C., Limoncelli, D. and Petrakis, I. (2007) The impact of personality disorders on alcohol-use outcomes in a pharmacotherapy trial for alcohol dependence and comorbid Axis I disorders. American Journal of Addictions, 16, 443-449. http://dx.doi.org/10.1080/1055049070 1643336
[40] Mutschler, J., Grosshans, M., Koopmann, A., Hermann, D., Diehl, A., Mann, K. and Kiefer, F. (2010) Supervised disulfiram in relapse prevention in alcohol-dependent patients suffering from comorbid borderline personality disorder—A case series. Alcohol and Alcoholism, 45, 146-150.
[41] Mutschler, J., Buhler, M., Grosshans, M., Diehl, A., Mann, K. and Kiefer, K. (2010) Disulfiram, an option for the treatment of pathological gambling? Alcohol and Alcoholism, 45, 214-216.
[42] Mutschler, J., Dirican, G., Gutzeit, A. and Grosshans, M. (2011) Safety and efficacy of long term disulfiram after care. Clinical Neuropharmacology, 34, 195-198. http://dx.doi.org/10.1097/WNF. 0b013e3182285e2d
[43] Niederhofer, H. and Staffen, W. (2003) Comparison of disulfiram and placebo in treatment of alcohol dependence of adolescents. Drug and Alcohol Review, 22, 295-297. http://dx.doi.org/10.1080/ 0959523031000154436
[44] De Sousa, A. anddence. Journal of Substance Use, 13, 382-388. De Sousa, A. (2008) An open randomized trial comparing disulfiram and naltrexone in adolescents with alcohol depen
[45] Verheul, R., Lehert, P., Geerlings, P.J., Koeter, M.W. and van den Brink, W. (2005) Predictors of acamprosate efficacy: Results from a pooled analysis of seven European trials including 1485 alcohol dependent patients. Psychopharmacology, 178, 167-173. http://dx.doi.org/10.1007/s00213-004-1991-7
[46] De Sousa, A. and De Sousa, A. (2004) A one-year pragmatic trial of naltrexone vsdisulfiram in the treatment of alcohol dependence. Alcohol& Alcoholism, 39, 528-531. http://dx.doi.org/10.1093/ alcalc/agh104
[47] De Sousa, A. and De Sousa, A. (2005) An open randomized study comparing disulfiram and acamprosate in the treatment of alcohol dependence. Alcohol and Alcoholism, 40, 545-548. http://dx.doi.org/10.1093/alcalc/agh187
[48] De Sousa, A.A., De Sousa, J. and Kapoor, H. (2008) An open randomized trial comparing disulfiram and topiramate in the treatment of alcohol dependence. Journal of Substance Abuse Treatment, 34, 460-463. http://dx.doi.org/10.1016/j.jsat.2007.05.012
[49] Berglund, M. (2005) A better widged? Three lessons for improving addiction treatment from a meta-analytical study. Addiction, 100, 742-750. http://dx.doi.org/10.1111/j.1360-0443.2005.01106.x
[50] Brewer, C., Meyers, R.J. and Johnsen, J. (2000) Does disulfiram help to prevent relapse in alcohol abuse? CNS Drugs, 14, 329-341. http://dx.doi.org/10.2165/00023210-200014050-00001
[51] Besson, J., Aeby, F., Kasas, A., Lehert, P. and Potgeiter, A. (1998) Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: A controlled study. Alcoholism: Clinical and Experimental Research, 22, 573-579. http://dx.doi.org/10.1111/j.1530-0277.1998.tb04295.x
[52] Laaksonen, E., Koski-Jannes, A., Salaspuro, M., Ahtinen, H. and Alho, H. (2008) A randomized, multicentre, openlabel, comparative trial of disulfiram, naltrexone and acamprosate in the treatment of alcohol dependence. Alcohol and Alcoholism, 43, 53-61. http://dx.doi.org/10.1093/alcalc/agm136
[53] Pettinati, H.M., Kampman, K.M., Lynch, K.G., Xie, H., Dackis, C., Rabinowitz, A.S. and O’Brien, C.P. (2007) A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence. Addiction Behaviour, 33, 651-667.
[54] Maremmani, A.G., Pani, P.P., Rovai, L., Pacini, M., Dell Osso, L. and Maremanni, L. (2011) Long-term ?-hydroxybutyric acid (GHB) and disulfiram combination therapy in GHB treatment-resistant chronic alcoholics. International Journal of Environmental Research & Public Health, 8, 2816-2827. http://dx.doi.org/10.3390/ijerph8072816
[55] Peachey, J.E. (1981) A review of the clinical use of disulfiram and calcium carbimide in alcoholism treatment. Journal of Clinical Psychopharmacology, 1, 368-375. http://dx.doi.org/10.1097/00004714-198111000-00004
[56] Sande, M., Thompson, D. and Monte, A.A. (2012) Fomepizole for severe disulfiram-ethanol reactions. American Journal of Emergency Medicine, 30, 262.e3-5.
[57] Heelon, M.W. and White, M. (1998) Disulfiram-cotrimoxazole reaction. Pharmacotherapy, 18, 869-870.
[58] Ho, M.P., Yo, C.H., Liu, C.M. Chen, C.L. and Lee, C.C. (2007) Refractive hypotension in a patient with disulfiram-ethanol reaction. American Journal of Medical Science, 333, 53-55.
[59] Savas, M.C. and Gullu, J.H. (1997) The disulfiram ethanol reaction: The significance of supervision. Annals of Pharmacotherapy, 31, 374-375.
[60] Nucifora, G., Cassin, M., Brun, F. and Nicolosi, G.L. (2004) Anterior myocardial infarction in a chronic alcoholic man on disulfiram therapy: A case report. Italian Heart Journal, 5, 900-904.
[61] Prancheva, M.G., Krasteva, S.A. and Tufkova, S.G. (2010) Severe hypotension and ischemic stroke after disulfiramethanol reaction. Folia Medica, 52, 70-73. http://dx.doi.org/10.2478/v10153-010-0009-y
[62] Ehrlich, R.I., Woolf, D.C. and Kibel, D.A. (2012) Disulfiram reaction in an artist exposed to solvents. Occupational Medicine, 62, 64-66. http://dx.doi.org/10.1093/occmed/kqr172
[63] Palatty, P.L. and Saldanha, E. (2011) Status of disulfiram in present day alcoholic deaddiction therapy. Indian Journal of Psychiatry, 53, 25-29. http://dx.doi.org/10.4103/0019-5545.75557
[64] Mutschler, J., Grosshans, M., Koopmann, A., Mann, K., Kiefer, F. and Hermann, D. (2010) Urinary ethylglucuronide assessment in patients treated with disulfiram: A tool to improve verification of abstention and safety. Clinical Neuropharmacology, 33, 285-287. http://dx.doi.org/10.1097/WNF.0 b013e3181fc9362
[65] Lindros, K.O., Stowell, A., Pikkarainen, P. and Salaspuro, M. (1981) The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: Its efficient management by 4-methylpyrazole. Alcoholism: Clinical & Experimental Research, 5, 528-530. http://dx.doi.org/10.1111/j.1530-0277.1981.tb05354.x
[66] Megarbane, B., Borron, S.W. and Baud, F.J. (2005) Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Medicine, 31, 189-195. http://dx.doi.org/10.1007/s00134-004-2521-0
[67] Bakke, S.A. and Laursen, S.B. (2011) Treatment with disulfiram can be dangerous. Ugeskrift for Laeger, 173, 3192-3193.
[68] Verbon, H. and de Jong, C.A. (2002) Psychosis during and after disulfiram use. Nederlands Tijdschrift Geneeskde, 146, 571-573.
[69] Murthy, K.K. (1997) Psychosis during disulfiram therapy for alcoholism. Journal of the Indian Medical Association, 95, 80-81.
[70] Quail, M. and Karelse, R.H. (1980) Disulfiram psychosis. A case report. South African Medical Journal, 57, 551-552.
[71] Chick, J. (1999) Safety issues concerning the use of disulfiram in treating alcohol dependence. Drug Safety, 20, 427-435. http://dx.doi.org/10.2165/00002018-199920050-00003
[72] Wright IIII, C., Vafier, J.A. and Lake, C.R. (1988) Disulfiram-induced fulminating hepatitis: Guidelines for liverpanel monitoring. Journal of Clinical Psychiatry, 49, 430-434.
[73] Enghusen, P.H., Loft, S. and Anderson, J.R. (1992) Disulfiram therapy-adverse drug reactions and interactions. Acta Psychiatrica Scandanavica, 86, 59-66.
[74] Trelohan, A. and Milea, D. (2011) Reversible optic neuropathy related to disulfiram. Journal Francais Ophthalmology, 34, 382.
[75] Lemoyne, S., Raemaekers, J. and Daems, J. (2009) Delayed and prolonged coma after acute disulfiram overdose. Acta Neurologica Belgica, 109, 231-234.
[76] Liddon, S.C. and Satran, R. (1967) Disulfiram (Antabuse) psychosis. American Journal of Psychiatry, 123, 12841289.
[77] Saddichha, S., Phutane, V. and Thirthalli, J. (2011) De novo dose-dependent catatonia due to Disulfiram therapy: A report and review. Journal of Clinical Pharmacology, 51, 285-286. http://dx.doi.org/10.1177/0091270010365556
[78] Stahl, S.M. (2008) Psychosis and schizophrenia. In: Stahl, S.M., Ed., Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications, 3rd Edition, Cambridge University Press, Cambridge, 294-297.
[79] Northoff, G. (2004) Neuroimaging and neurophysiology. In: Caroff, S.N., Mann, S.C., Francis, A. and Fricchione, G.L., Eds., Catatonia: From psychopathology to neurobiology, American Psychiatric Publishing, Washington, DC, 77-91.
[80] Jagadisha, T. and Prabhat, C.K. (2009) The implications of medication development in the treatment of substance use disorders in developing countries. Current Opinion in Psychiatry, 22, 274-280. http://dx.doi.org/10.1097/YCO.0b013e32832a1dc0
[81] Diehl, A., Ulmer, L., Mutschler, J., Herre, H., Krumm, B., Croissant, B., Mann, K. and Kiefer, F. (2010) Why is disulfiram superior to acamprosate in the routine clinical setting? A retrospective long-term study in 353 alcoholdependent patients. Alcohol & Alcoholism, 45, 271-277. http://dx.doi.org/ 10.1093/alcalc/agq017
[82] Grover, S., Basu, D. and Bhateja, G. (2007) Pharmacoprophylaxis of alcohol dependence: Review and update Part II: Efficacy. Indian Journal of Psychiatry, 49, 26-33. http://dx.doi.org/10.4103/0019-5545.31515
[83] Sharma, P., Murthy, P. and Bharath, M.M. (2011) Disulfiram in a “traditional” medicine sold to patients with alcohol dependence in India. Addiction, 106, 1870-1871. http://dx.doi.org/10.1111/j.1360-0443.2011.03506.x
[84] Johnsen, J. and Morland, J. (1991) Disulfiram implant: A double-blind placebo controlled follow-up on treatment outcome. Alcoholism: Clinical and Experimental Research, 15, 532-536.
[85] O’Farrell, T.J., Allen, J.P. and Litten, R.Z. (1995) Disulfiram (antabuse) contracts in treatment of alcoholism. NIDA Research Monograph, 150, 65-91.
[86] Johnsen, J., Stowell, A. and Stensrud, T. (1990) A doubleblind placebo controlled study of healthy volunteers given a subcutaneous disulfiram implantation. Pharmacology & Toxicology, 66, 227-230. http://dx.doi.org/10.1111/j.1600-0773.1990.tb00738.x
[87] Anton, R.F., Oroszi, G., O’Malley, S.,Couper, D., Swift, R., Pettinati, H. and Goldman, D. (2008) An evaluation of μ-Opioid Receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence. JAMA Psychiatry, 65, 135-144. http://dx.doi.org/10.1001/archpsyc.65.2.135
[88] Oslin, D.W., Berrettini, W., Kranzler, H.R., Pettinati, H., Gerlenter, J., Volpicelli, J.R. and O’Brien, C.P. (2003) A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology, 28, 1546-1552.
[89] Kiefer, F., Witt, S.H., Frank, J., et al. (2011) Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate. Pharmacogenomics Journal, 11, 368-374. http://dx.doi.org/10.1038/tpj.2010.51

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.