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Fortschr Neurol Psychiatr 2008; 76(4): 225-231
DOI: 10.1055/s-2007-1016438
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Klinische Pharmakologie von Disulfiram - eine aktuelle Übersicht[1]

Pharmacology of Disulfiram - An UpdateJ.  Mutschler1 , A.  Diehl1 , F.  Kiefer1
  • 1Klinik für Abhängiges Verhalten und Suchtmedizin, Zentralinstitut für Seelische Gesundheit, Mannheim
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Publication Date:
07 February 2008 (online)

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Zusammenfassung

Der gegenwärtig zu beobachtende Anstieg an Verschreibungen von Disulfiram setzt ärztliche Kenntnisse bezüglich Pharmakodynamik, -kinetik, Nebenwirkung und Wechselwirkung der Substanz voraus. Wir geben eine Übersicht über die Pharmakologie und unerwünschte Nebenwirkungen der Substanz Disulfiram. Beispielhaft wird ein Fall vorgestellt, bei welchem ein akutes neurologisches Defizit zunächst als Nebenwirkung von Disulfiram verkannt wurde. Diskutiert werden mögliche Perspektiven von Disulfiram in der Suchtmedizin.

Abstract

Recently, we have been observing an increase in prescription of Disulfiram requiring medical knowledge concerning the overall effects, side effects and drug interactions of this substance. In the following report, we give an overview about the pharmacology and the side effects of Disulfiram. As an example we demonstrate a case, in which an acute neurological deficit was misjudged as a side effect of Disulfiram. Furthermore, the potential of Disulfiram as a promising treatment in addiction medicine will be discussed.

Schlüsselwörter

Disulfiram - Alkohol - Nebenwirkungen - Wechselwirkungen - Arzneimittel-Interaktionen

Key words

Disulfiram - alcohol - side effects - adverse drug reactions - drug interactions

1 Interessenkonflikt. Es besteht kein Interessenkonflikt. Die Autoren versichern, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Literatur

  • 1 De Sousa A, De Sousa A. A one-year pragmatic trial of naltrexone vs disulfiram in the treatment of alcohol dependence.  Alcohol Alcohol. 2004;  39 528-531
    Search in Google Scholar
  • 2 De Sousa A, De Sousa A. An open randomized study comparing disulfiram and acamprosate in the treatment of alcohol dependence.  Alcohol Alcohol. 2005;  40 545-548
    Search in Google Scholar
  • 3 Krampe H, Stawicki S, Wagner T. et al . Follow-up of 180 alcoholic patients for up to 7 years after outpatient treatment: impact of alcohol deterrents on outcome.  Alcohol Clin Exp Res. 2006;  30 86-95
    Search in Google Scholar
  • 4 Chick J, Gough K, Falkowski W. et al . Disulfiram treatment of alcoholism.  Br J Psychiatry. 1992;  161 84-89
    Search in Google Scholar
  • 5 Datenlieferungen nach § 300 SGB V, Wissenschaftliches Institut der AOK WldO. 2007
    Search in Google Scholar
  • 6 Johansson B. A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites.  Acta Psychiatr Scand Suppl. 1992;  369 15-26
    Search in Google Scholar
  • 7 Brewer C. How effective is the standard dose of disulfiram? A review of the alcohol-disulfiram reaction in practice.  Br J Psychiatry. 1984;  144 200-202
    Search in Google Scholar
  • 8 Madan A, Parkinson A, Faiman M D. Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation of diethyldithiocarbamate methyl ester: role of P-450 enzymes in disulfiram bioactivation.  Alcohol Clin Exp Res. 1998;  22 1212-1219
    Search in Google Scholar
  • 9 Elenbaas R M. Drug therapy reviews: management of the disulfiram-alcohol reaction.  Am J Hosp Pharm. 1977;  34 827-831
    Search in Google Scholar
  • 10 Amadoe M, Gazdar A. Sudden death during disulfiram-alcohol reaction.  Q J Stud Alcohol. 1967;  28 649-654
    Search in Google Scholar
  • 11 Guild J, Epstein N B. Psychosis during the treatment of alcoholism with tetraethylthiuram disulfide.  Q J Stud Alcohol. 1951;  12 360-366
    Search in Google Scholar
  • 12 Jacobsen E. Deaths of alcoholic patients treated with disulfiram (tetraethylthiuram disulfide) in Denmark.  Q J Stud Alcohol. 1952;  13 16-26
    Search in Google Scholar
  • 13 Fuller R K, Branchey L, Brightwell D R. et al . Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.  JAMA. 1986;  256 1449-1455
    Search in Google Scholar
  • 14 Fuller R K, Gordis E. Does disulfiram have a role in alcoholism treatment today?.  Addiction. 2004;  99 21-24
    Search in Google Scholar
  • 15 Green A L. The inhibition of dopamine-B-oxidase by chelating agents.  Biochem biophys Acta. 1964;  81 394-397
    Search in Google Scholar
  • 16 Mays D C, Ortiz-Bermudez P, Lam J P, Tong I H, Fauq A H, Lipsky J J. Inhibition of recombinant human mitochondrial aldehyde dehydrogenase by two intermediate metabolites of disulfiram.  Biochem Pharmacol. 1998;  55 1099-1103
    Search in Google Scholar
  • 17 Karamanakos P N, Pappas P, Stephanou P, Marselos M. Differentiation of disulfiram effects on central catecholamines and hepatic ethanol metabolism.  Pharmacol Toxicol. 2001;  88 106-110
    Search in Google Scholar
  • 18 Musacchio J M, Goldstein M, Anagnoste B, Poch G, Kopin I J. Inhibition of dopamine-beta-hydroxylase by disulfiram in vivo.  J Pharmacol Exp Ther. 1966;  152 56-61
    Search in Google Scholar
  • 19 Paradisi R, Grossi G, Pintore A. et al . Evidence for a pathological reduction in brain dopamine metabolism in idiopathic hyperprolactinemia.  Acta Endocrinol (Copenh). 1991;  125 246-252
    Search in Google Scholar
  • 20 Rosen G F, Lobo R A. Further evidence against dopamine deficiency as the cause of inappropriate gonadotropin secretion in patients with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1987;  65 891-895
    Search in Google Scholar
  • 21 Amit Z, Levitan D E, Lindros K O. Suppression of ethanol intake following administration of dopamine-beta-hydroxylase inhibitors in rats.  Arch Int Pharmacodyn Ther. 1976;  223 114-119
    Search in Google Scholar
  • 22 Kohnke M D, Zabetian C P, Anderson G M. et al . A genotype-controlled analysis of plasma dopamine beta-hydroxylase in healthy and alcoholic subjects: evidence for alcohol-related differences in noradrenergic function.  Biol Psychiatry. 2002;  52 1151-1158
    Search in Google Scholar
  • 23 Kohnke M D, Kolb W, Kohnke A M, Lutz U, Schick S, Batra A. DBH*444G/A polymorphism of the dopamine-beta-hydroxylase gene is associated with alcoholism but not with severe alcohol withdrawal symptoms.  J Neural Transm. 2006;  113 869-876
    Search in Google Scholar
  • 24 Ewing J A, Rouse B A, Mueller R A, Silver D. Can dopamine beta-hydroxylase levels predict adverse reactions to disulfiram?.  Alcohol Clin Exp Res. 1978;  2 93-94
    Search in Google Scholar
  • 25 Heath R G, Nesselhof Jr  W, Bishop M P, Byers L W. Behavioral and metabolic changes associated with administration of tetraethylthiuram disulfide (antabuse).  Dis Nerv Syst. 1965;  26 99-105
    Search in Google Scholar
  • 26 Major L F, Lerner P, Ballenger J C, Brown G L, Goodwin F K, Lovenberg W. Dopamine-beta-hydroxylase in the cerebrospinal fluid: relationship to disulfiram-induced psychosis.  Biol Psychiatry. 1979;  14 337-344
    Search in Google Scholar
  • 27 Cubells J F, Kranzler H R, Cance-Katz E. et al . A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia.  Mol Psychiatry. 2000;  5 56-63
    Search in Google Scholar
  • 28 Poikolainen K. The disulfiram-ethanol reaction (DER) experience.  Addiction. 2004;  99 6-28
    Search in Google Scholar
  • 29 Ehrenreich H, Krampe H. Does disulfiram have a role in alcoholism treatment today? Not to forget about disulfiram's psychological effects.  Addiction. 2004;  99 26-27
    Search in Google Scholar
  • 30 Martensen-Larsen O. Psychotic phenomena provoked by tetraethylthiuram disulfide.  Q J Stud Alcohol. 1951;  12 206-216
    Search in Google Scholar
  • 31 Christensen J K, Ronsted P, Vaag U H. Side effects after disulfiram. Comparison of disulfiram and placebo in a double-blind multicentre study.  Acta Psychiatr Scand. 1984;  69 265-273
    Search in Google Scholar
  • 32 Fuller R K, Branchey L, Brightwell D R. et al . Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.  JAMA. 1986;  256 1449-1455
    Search in Google Scholar
  • 33 Poulsen H E. Disulfiram therapy - adverse drug reactions and interactions. Loft S, Andersen JR, Andersen M (eds).  Acta Psychiatr Scand. 1992;  86 59-66
    Search in Google Scholar
  • 34 Branchey L, Davis W, Lee K K, Fuller R K. Psychiatric complications of disulfiram treatment.  Am J Psychiatry. 1987;  144 1310-1312
    Search in Google Scholar
  • 35 Bjornsson E, Nordlinder H, Olsson R. Clinical characteristics and prognostic markers in disulfiram-induced liver injury.  J Hepatol. 2006;  44 791-797
    Search in Google Scholar
  • 36 Frisoni G B, Di Monda V. Disulfiram neuropathy: a review (1971 - 1988) and report of a case.  Alcohol Alcohol. 1989;  24 429-437
    Search in Google Scholar
  • 37 Berglund M. A better widget? Three lessons for improving addiction treatment from a meta-analytical study.  Addiction. 2005;  100 742-750
    Search in Google Scholar
  • 38 Mann K, Lehert P, Morgan M Y. The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals: results of a meta-analysis.  Alcohol Clin Exp Res. 2004;  28 (1) 51-63
    Search in Google Scholar
  • 39 Kiefer F, Jahn H, Tarnaske T. et al . Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study.  Arch Gen Psychiatry. 2003;  60 92-99
    Search in Google Scholar
  • 40 Besson J, Aeby F, Kasas A, Lehert P, Potgieter A. Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism: a controlled study.  Alcohol Clin Exp Res. 1998;  22 573-579
    Search in Google Scholar
  • 41 Landabaso M A, Iraurgi I, Sanz J. et al . Naltrexone in the treatment of alcoholism. Two-year follow up results.  Eur J Psychiatry. 1999;  13 97-105
    Search in Google Scholar
  • 42 Petrakis I L, Poling J, Levinson C, Nich C, Carroll K, Rounsaville B. Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders.  Biol Psychiatry. 2005;  57 1128-1137
    Search in Google Scholar
  • 43 Petrakis I L, Poling J, Levinson C. et al . Naltrexone and disulfiram in patients with alcohol dependence and comorbid post-traumatic stress disorder.  Biol Psychiatry. 2006;  60 777-783
    Search in Google Scholar
  • 44 Weinshenker D, Schroeder J P. There and Back Again: A Tale of Norepinephrine and Drug Addiction.  Neuropsychopharmacology. 2007;  32 1433-1451
    Search in Google Scholar
  • 45 Finney J W, Monahan S C. The cost-effectiveness of treatment for alcoholism: a second approximation.  J Stud Alcohol. 1996;  57 229-243
    Search in Google Scholar
  • 46 Miller W R, Wilbourne P L. Mesa Grande: a methodological analysis of clinical trials of treatments for alcohol use disorders.  Addiction. 2002;  97 265-277
    Search in Google Scholar
  • 47 Fuller R K, Branchey L, Brightwell D R. et al . Disulfiram treatment of alcoholism. A Veterans Administration cooperative study.  JAMA. 1986;  256 1449-1455
    Search in Google Scholar
  • 48 Kellam A M, Wesolkowski J M. Disulfiram implantation for alcoholism.  Lancet. 1968;  1 925-926
    Search in Google Scholar
  • 49 Wilson A, Davidson W J, Blanchard R, White J. Disulfiram implantation. A placebo-controlled trial with two-year follow-up.  J Stud Alcohol. 1978;  39 809-819
    Search in Google Scholar
  • 50 Hughes J C, Cook C C. The efficacy of disulfiram: a review of outcome studies.  Addiction. 1997;  92 381-395
    Search in Google Scholar
  • 51 Suh J J, Pettinati H M, Kampman K M, O"Brien C P. The status of disulfiram: a half of a century later.  J Clin Psychopharmacol. 2006;  26 290-302
    Search in Google Scholar
  • 52 Matching Alcoholism Treatments to Client Heterogeneity . Project MATCH posttreatment drinking outcomes.  J Stud Alcohol. 1997;  58 7-29
    Search in Google Scholar
  • 53 Moos R H, Finney J W, Ouimette P C, Suchinsky R T. A comparative evaluation of substance abuse treatment: I. Treatment orientation, amount of care, and 1-year outcomes.  Alcohol Clin Exp Res. 1999;  23 529-536
    Search in Google Scholar
  • 54 Brewer C. Long-term, high-dose disulfiram in the treatment of alcohol abuse.  Br J Psychiatry. 1993;  163 687-689
    Search in Google Scholar
  • 55 Carroll K M, Fenton L R, Ball S A. et al . Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial.  Arch Gen Psychiatry. 2004;  61 264-272
    Search in Google Scholar
  • 56 Fritze J. Psychopharmaka-Verordnungen - Ergebnisse und Kommentare zum Arzneiverordnungsreport 2005.  Psychoneuro. 2006;  32 44-53
    Search in Google Scholar
  • 57 Kiefer F, Jahn H, Holzbach R, Briken P, Stracke R, Wiedemann K. Die NALCAM-Studie: Wirksamkeit, Verträglichkeit, Outcome.  Sucht. 2003;  49 (6) 342-351
    Search in Google Scholar

1 Interessenkonflikt. Es besteht kein Interessenkonflikt. Die Autoren versichern, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen. Die Präsentation des Themas ist unabhängig und die Darstellung der Inhalte produktneutral.

Dr. med. Alexander Diehl

Klinik für Abhängiges Verhalten und Suchtmedizin, Ärztlicher Direktor Prof. Dr. Karl Mann, Zentralinstitut für Seelische Gesundheit

Quadrat J 5

68159 Mannheim

Email: alexander.diehl@zi-mannheim.de