Disease Management and Health Outcomes

, Volume 3, Issue 1, pp 35–46 | Cite as

Management of Alcohol Dependence after Detoxification

The Potential Role of Acamprosate
Drugs in Disease Management

Abstract

Alcohol dependence is a major health problem associated with substantial social and healthcare costs. Until recently, the only available management options for maintaining abstinence in alcohol-dependent patients after detoxification were psychosocial/behavioural therapies (including self-help groups) and aversive therapies such as disulfiram. Although these approaches can reduce alcohol intake, their efficacy is limited and aversive therapy is associated with potentially serious adverse events and poor patient compliance.

A greater understanding of the neurobiology of alcohol dependence has resulted in the investigation of a range of agents with effects on the various neurotransmitters and neuromodulators involved in this condition. Acamprosate, a glutamatergic agent, and naltrexone, an opioid antagonist, have shown the most promise; acamprosate has been the most extensively studied.

Acamprosate is the first agent to be developed specifically for the prevention of relapse in detoxified alcohol-dependent patients. This well tolerates drug increases mean continuous alcohol abstinence rates, the cumulative duration of abstinence and the time to first alcoholic drink compared with placebo. Its efficacy may be enhanced by the addition of disulfiram.

Comparative trials with naltrexone and other active treatment approaches are required before the definitive position of acamprosate can be determined. In the meantime, acamprosate, as an adjunct to psychosocial/behavioural therapies (including counselling), can be considered a promising first-line pharmacological therapy for the maintenance of abstinence in detoxified alcohol-dependent patients.

Keywords

Adis International Limited Alcohol Dependence Naltrexone Buspirone Disulfiram 

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References

  1. 1.
    Wilde MI, Wagstaff AJ. Acamprosate: a review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification. Drugs. 1997 Jun; 53: 1038–53.PubMedCrossRefGoogle Scholar
  2. 2.
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington DC: American Psychiatric Association, 1994: 176–181.Google Scholar
  3. 3.
    Lesch OM, Walter H. Subtypes of alcoholism and their role in therapy. Alcohol Alcohol. 1996 Mar; 31 Suppl 1: 63–7.PubMedGoogle Scholar
  4. 4.
    McKenna M, Chick J, Buxton M, et al. The SECCAT survey: I. The costs and consequences of alcoholism. Alcohol Alcohol. 1996 Nov; 31: 565–76.PubMedGoogle Scholar
  5. 5.
    Schuckit MA. Alcohol and alcoholism. In: Wilson JD, Braunwald E, et al., editors. Harrison’s principles of internal medicine. 12th ed. vol. 2. USA: McGraw-Hill Inc., 1991: 2146–51.Google Scholar
  6. 6.
    Peters DH, Faulds D. Tiapride: a review of its pharmacology and therapeutic potential in the management of alcohol dependence syndrome. Drugs. 1994 Jun; 47: 1010–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Maynard A, Godfrey C. Alcohol policy — evaluating the options. Br Med Bull. 1994 Jan; 50: 221–30.PubMedGoogle Scholar
  8. 8.
    Chick J. Acamprosate as an aid in the treatment of alcoholism. Alcohol Alcohol. 1995 Nov; 30: 785–7.PubMedGoogle Scholar
  9. 9.
    Rassnick S, D’Amico E, Riley E, et al. GABA and nucleus accumbens glutamate neurotransmission modulate ethanol self-administration in rats. Ann N Y Acad Sci. 1992 Jun 28; 654: 502–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Littleton J. Acamprosate in alcohol dependence: how does it work? Addiction. 1995; 90: 1179–88.PubMedCrossRefGoogle Scholar
  11. 11.
    Durbin P, Hulot T, Chabac S. Pharmacodynamics and pharmacokinetics of acamprosate: an overview. In: Soyka M, editor. Acamprosate in relapse prevention of alcoholism. Proceedings of the 1st Campral-symposium ESBRA. Stuttgart: Springer, 1995: 47–64.Google Scholar
  12. 12.
    Soyka M. Relapse prevention in alcoholism. Recent advances and future possibilities. CNS Drugs. 1997; 7(4): 313–27.CrossRefGoogle Scholar
  13. 13.
    Gianoulakis C. Implications of endogenous opioids and dopamine in alcoholism: human and basic science studies. Alcohol Alcohol. 1996; 31 Suppl. 1: 33–42.PubMedGoogle Scholar
  14. 14.
    De Witte P. The role of neurotransmitters in alcohol dependence: animal research. Alcohol Alcohol. 1996; 31 Suppl. 1: 13–6.PubMedGoogle Scholar
  15. 15.
    Lewis MJ. Alcohol reinforcement and neuropharmacological therapeutics. Alcohol Alcohol. 1996; 31 Suppl.1: 17–25.PubMedGoogle Scholar
  16. 16.
    Boyadjieva N, Reddy BV, Sarkar DK. Forskolin delays the ethanol-induced desensitization of hypothalamic β-endorphin neurons in primary cultures. Alcohol Clin Exp Res. 1997; 21(3): 477–82.PubMedCrossRefGoogle Scholar
  17. 17.
    Adams ML, Cicero TJ. Effects of alcohol on β-endorphin and reproductive hormones in the male rat. Alcohol Clin Exp Res. 1991; 15(4): 685–92.PubMedCrossRefGoogle Scholar
  18. 18.
    Gianoulakis C, Krishnan B, Thavundayil J. Enhanced sensitivity of pituitary β-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry. 1996; 53: 250–7.PubMedCrossRefGoogle Scholar
  19. 19.
    De Waele J-P, Papachristou DN, Gianoulakis C. The alcoholpreferring C57BL/6 mice present an enhanced sensitivity of the hypothalamic β-endorphin system to ethanol than the alcohol-avoiding DBA/2 mice. J Pharmacol Exp Ther. 1992; 261(2): 788–94.PubMedGoogle Scholar
  20. 20.
    Charness ME. Ethanol and opioid receptor signalling. Experientia. 1989; 45: 418–28.PubMedCrossRefGoogle Scholar
  21. 21.
    Lesch OM, Walter H, Bonte W. Etiology of subgroups in chronic alcoholism and different mechanisms in transmitter systems. In: Palmer TN, editor. Alcoholism: a molecular Perspective. New York: Plenum Press,. 1991; 206: 145–60.Google Scholar
  22. 22.
    Heizer JE, Burnam A, McEvoy LT. Alcohol abuse and dependence. In: Robins CN, Regier DA, editors. Psychiatric disorders in America: the epidemiologic catchment area study. New York: Free Press, 1991: 81–115.Google Scholar
  23. 23.
    Grant BF, Harford TC, Dawson DA, et al. Epidemiologic bulletin no. 35: prevalence of DSM-IV alcohol abuse and dependence: United States, 1992. Alcohol Health Res World. 1991; 18: 243–8.Google Scholar
  24. 24.
    Batel P. The treatment of alcoholism in France. Drug Alcohol Depend 1995 Sep; 39 Suppl. 1: S15–21.PubMedCrossRefGoogle Scholar
  25. 25.
    Robins LN, Heizer JE, Weissman MM, et al. Lifetime prevalence of specific psychiatric disorders in three sties. Arch Gen Psychiatry. 1984; 41: 949–58.PubMedCrossRefGoogle Scholar
  26. 26.
    McCrady BS, Langenbucher JW. Alcohol treatment and health care system reform. Arch Gen Psychiatry 1996 Aug; 53: 737–46.PubMedCrossRefGoogle Scholar
  27. 27.
    Dongier M. Brain, alcohol and alcoholism treatment. Ann R Coll Phys Surg Can. 1993; 26(1): 26–8.Google Scholar
  28. 28.
    Rice DP. The economic cost of alcohol abuse and alcohol dependence: 1990. Alcohol Health Res World. 1993; 17: 10–1.Google Scholar
  29. 29.
    Rice DP, Kelman S, Miller LS, et al. The economic costs of alcohol and drug abuse and mental illness: 1985a. Report submitted to the Office of Financing and Coverage Policy of the Alcohol, Drug Abuse, and Mental Health Administration, US Department of Health and Human Services, San Francisco (CA): Institute for Health and Aging, University of California, 1990.Google Scholar
  30. 30.
    Brecht JG, Poldrugo F, Schädlich PK. Alcoholism: the cost of illness in the Federal Republic of Germany. Pharmacoeconomics. 1996 Nov; 10: 484–93.PubMedCrossRefGoogle Scholar
  31. 31.
    Goodman AC, Holder HD, Nishiura E. An analysis of shortterm alcoholism treatment cost functions. Med Care. 1992 Sep; 30: 795–810.PubMedCrossRefGoogle Scholar
  32. 32.
    Rice DP. The economic cost of alcohol abuse and alcohol dependence: 1990. Alcohol Health Res World. 1993; 17(1): 10–1.Google Scholar
  33. 33.
    Howard MO, McGuffin RW, Saxon AJ, et al. Clinical issues related to the costs of alcoholism. Pharmacoeconomics. 1996 Feb; 9: 134–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Mayo-Smith MF, American S of AMW group on PM of AW. Pharmacological management of alcohol withdrawal: a metaanalysis and evidence-based practice guideline. JAMA. 1997 Jul 9; 278: 144–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Naranjo CA, Ozdemir V, Bremner KE. Diagnosis and pharmacological treatment of alcoholic patients. CNS Drugs. 1994 May; 1: 330–40.CrossRefGoogle Scholar
  36. 36.
    Litten RZ, Allen J, Fertig J. Pharmacotherapies for alcohol problems: a review of research with focus on developments since 1991. Alcohol Clin Exp Res. 1996 Aug; 20: 859–76.PubMedCrossRefGoogle Scholar
  37. 37.
    Boismare F, Daoust M, Lhuintre JP, et al. Which GABA receptors are involved in the voluntary ethanol intake by rats? [abstract]. Alcohol Alcohol 1986; 21: A30.Google Scholar
  38. 38.
    O’Malley SS. Current strategies for the treatment of alcohol dependence in the United States. Drug Alcohol Depend 1995 Sep; 39 Suppl. 1: S3–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Perlmutter SJ. Pharmacologic treatment of substance abuse. Child Adolesc Psychiatr Clin North Am. 1995; 4(2): 435–52.Google Scholar
  40. 40.
    Verbanck PM. The pharmacological treatment of alcoholism: from basic science to clinical medicine. Alcohol Alcohol. 1995 Nov; 30: 757–64.PubMedGoogle Scholar
  41. 41.
    Boismare F, Daoust M, Moore N, et al. A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved? Pharmacol Biochem Behav 1984 Nov; 21: 787–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Berg BJ, Pettinati HM, Volpicelli JR. A risk-benefit assessment of naltrexone in the treatment of alcohol dependence. Drug Saf. 1996 Oct; 15: 274–82.PubMedCrossRefGoogle Scholar
  43. 43.
    Anton RE. Neurobehavioural basis for the pharmacotherapy of alcoholism: current and future directions. Alcohol Alcohol 1996; 31 Suppl. 1: 43–53.PubMedGoogle Scholar
  44. 44.
    Del Boca FK, Mattson ME. Developments in alcoholism treatment research: patient-treatment matching. Alcohol. 1994; 11(6): 471–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Sperling W, Lesch OM. The reduction of alcohol consumption with novel pharmacological intervention. Eur Psychiatry. 1996; 11: 217–26.PubMedCrossRefGoogle Scholar
  46. 46.
    Volpicelli JR, Volpicelli LA, O’Brien CR. Medical management of alcohol dependence: clinical use and limitations of naltrexone treatment. Alcohol Alcohol 1995 Nov; 30: 789–98.PubMedGoogle Scholar
  47. 47.
    Hughes JC, Cook CC. The efficacy of disulfiram: a review of outcome studies. Addiction. 1997 Apr; 92: 381–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Chick J. Emergent treatment concepts. Annu Rev Addict Res Treat. 1992; 2: 297–312.Google Scholar
  49. 49.
    O’Malley SS. Opioid antagonists in the treatment of alcohol dependence: clinical efficacy and prevention of relapse. Alcohol Alcohol. 1996 Mar; 31 Suppl. 1: 77–81.PubMedGoogle Scholar
  50. 50.
    Sellers EM, Higgins GA, Tomkins DM, et al. Opportunities for treatment of psychoactive substance use disorders with serotonergic medications. J Clin Psychiatry 1991 Dec; 52 Suppl.: 49–54.PubMedGoogle Scholar
  51. 51.
    Lejoyeux M. Use of serotonin (5-hydroxytryptamine) reuptake inhibitors in the treatment of alcoholism. Alcohol Alcohol. 1996 Mar; 31 Suppl. 1: 69–75.PubMedGoogle Scholar
  52. 52.
    Gorelick DA. Medications for the treatment of substance abuse. Curr Opin Psychiatry. 1992; 5(3): 430–5.CrossRefGoogle Scholar
  53. 53.
    Zernig G, Fabisch K, Fabisch H. Pharmacotherapy of alcohol dependence. Trends Pharmacol Sci. 1997; 18: 229–31.PubMedGoogle Scholar
  54. 54.
    Kranzler HR. Evaluation and treatment of anxiety symptoms and disorders in alcoholics. J Clin Psychiatry. 1996; 57 Suppl. 7: 15–21.PubMedGoogle Scholar
  55. 55.
    Malec TS, Malec EA, Dongier M. Efficacy of buspirone in alcohol dependence: a review. Alcohol Clin Exp Res. 1996 Aug; 20: 853–8.PubMedCrossRefGoogle Scholar
  56. 56.
    Mueller TI, Stout RL, Rudden S, et al. A double-blind, placebocontrolled pilot study of carbamazepine for the treatment of alcohol dependence. Alcohol Clin Exp Res. 1997 Feb; 21: 86–92.PubMedCrossRefGoogle Scholar
  57. 57.
    Gallimberti L, Ferri M, Ferrara SD, et al. Gamma-hydroxybutyric acid in the treatment of alcohol dependence: a double-blind study. Alcohol Clin Exp Res. 1992; 16(4): 673–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Monti JM, Alterwain P. Ritanserin decreases alcohol intake in chronic alcoholics [letter]. Lancet. 1991; 337: 60.PubMedCrossRefGoogle Scholar
  59. 59.
    Lipha. Campral, Prescribing information. European summary of product characteristics, Lyon, France, 1995.Google Scholar
  60. 60.
    Durlach J, Rinjard P, Sprince H, et al. Similar antagonistic effects of Ca N-acetylhomotaurinate on depression of motor activity and lethality induced by acetaldehyde or ethanol. Methods Find Exp Clin Pharmacol. 1988 Jul; 10: 437–47.PubMedGoogle Scholar
  61. 61.
    Zeise ML, Kasparov S, Capogna M, et al. Acamprosate (calciumacetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitory amino acid receptors. Eur J Pharmacol. 1993 Jan 26; 231: 47–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Zieglgänsberger W, Hauser C, Putzke J, et al. Acamprosate reduces the enhanced excitability of central neurons following chronic alcohol intake [abstract]. Pharmacopsychiatry. 1995 Sep; 28: 231.Google Scholar
  63. 63.
    Nalpas B, Dabadie H, Parot P, et al. Acamprosate: from pharmacology to therapeutics [in French]. Encephale. 1990 May–Jun; 16: 175–9.PubMedGoogle Scholar
  64. 64.
    Bouchenafa O, El-Qatari M, Khan S, et al. Potential mechanisms of action of the anti-craving drug, acamprosate, in alcohol dependence [abstract]. Behav Pharmacol. 1995 Aug; 6: 614.CrossRefGoogle Scholar
  65. 65.
    Madamba SG, Schweitzer P, Zieglgänsberger W, et al. Acamprosate (calcium acetylhomotaurinate) enhances the N-methyl-D-aspartate component of excitatory neurotransmission in rat hippocampal CA1 neurons in vitro. Alcohol Clin Exp Res. 1996; 20(4): 651–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Spanagel R, Zieglgänsberger W. Anti-craving compounds for ethanol: new pharmacological tools to study addictive processes. Trends Pharmacol Sci. 1997; 18: 54–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Le Magnen J, Tran G, Durlach J, et al. Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate. Alcohol. 1987 Mar–Apr; 4: 97–102.PubMedCrossRefGoogle Scholar
  68. 68.
    Le Magnen J, Tran G, Durlach J. Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats. Alcohol. 1987 Mar–Apr; 4: 103–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Grant KA, Woolverton WL. Reinforcing and discriminative stimulus effects of Ca-acetyl homotaurine in animals. Pharmacol Biochem Behav. 1989 Mar; 32: 607–11.PubMedCrossRefGoogle Scholar
  70. 70.
    Besson J, Aeby F, Kasas A, et al. Combined efficacy of acamprosate and disulfiram for enhancing abstinence of chronic alcoholic patients during a one year post detoxication period [abstract]. Neuropsychopharmacology 1994 May; 10 Suppl. (Pt 2): 74S.Google Scholar
  71. 71.
    Ladewig D, Knecht T, Leher P, et al. Acamprosate — a stabilising factor in the long-term treatment of alcoholics [in German]. Ther Umsch. 1993 Mar; 50: 182–8.PubMedGoogle Scholar
  72. 72.
    Lhuintre JP, Moore N, Tran G, et al. Acamprosate appears to decrease alcohol intake in weaned alcoholics. Alcohol Alcohol. 1990; 25: 613–22.PubMedGoogle Scholar
  73. 73.
    Paille FM, Guelfi JD, Perkins AC, et al. Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol. Alcohol Alcohol. 1995 Mar; 30: 239–47.PubMedGoogle Scholar
  74. 74.
    Pelc I, Le Bon O, Lehert P, et al. Acamprosate in the treatment of alcohol dependence: a 6-month postdetoxifcation study. In: Soyka M, editor. Acamprosate in relapse prevention of alcoholism. Proceedings of the lst Campral-symposium ESBRA. Stuttgart: Springer, 1996: 133–142.CrossRefGoogle Scholar
  75. 75.
    Sass H, Soyka M, Mann K, et al. Relapse prevention by acamprosate: results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiatry. 1996 Aug; 53: 673–80.PubMedCrossRefGoogle Scholar
  76. 76.
    Tempesta E, Janiri L, Bignamini AA. The effectiveness and safety of calcium-acetylhomotaurinate (acamprosate) on the maintenance of abstinence in weaned alcoholics [abstract]. Eur Psychiatry 1994; 9 Suppl. 1: 203.Google Scholar
  77. 77.
    Whitworth AB, Fischer F, Lesch OM, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996 May 25; 347: 1438–42.PubMedCrossRefGoogle Scholar
  78. 78.
    Geerlings PJ, Ansoms C, van den Brink W. Acamprosate and prevention of relapse in alcoholics. Results of a randomized, placebo-controlled, double-blind study in out-patient alcoholics in the Netherlands, Belgium and Luxembourg. Eur Addict Res. 1997; 3: 129–37.CrossRefGoogle Scholar
  79. 79.
    Sass H, Potgieter AS, Lehert P. Results from a pooled analysis of 11 European trials comparing acamprosate and placebo in the treatment of alcohol dependence [abstract]. Alcohol Alcohol 1995; 30(4): 551.Google Scholar
  80. 80.
    Delgrange T, Khater J, Capron D, et al. Effect of acute administration of acamprosate on the risk of hepatic encephalopathy and on blood pressure in alcoholic cirrhotic patients [in French]. Gastroenterol Clin Biol. 1992; 16: 687–91.PubMedGoogle Scholar
  81. 81.
    Spanagel R, Zieglgansberger W, Hundt W. Acamprosate and alcohol: III. Effects on alcohol discrimination in the rat. Eur J Pharmacol. 1996 Jun 3; 305: 51–6.PubMedCrossRefGoogle Scholar
  82. 82.
    Acamprosate helps maintain abstinence from alcohol after detoxification. Drug Ther Perspect 1997 Sep 1; 10 (5): 1–5.Google Scholar
  83. 83.
    Schädlich PK, Brecht JG. Cost-effectiveness of acamprosate in relapse prevention in alcoholism in Germany. ICAAA Congress, Amsterdam, 1996.Google Scholar

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© Adis International Limited 1998

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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