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Relapse Prevention by Acamprosate: Results From a Placebo-Controlled Study on Alcohol Dependence

Relapse Prevention by Acamprosate: Results From a Placebo-Controlled Study on Alcohol Dependence Abstract Background The effectiveness acamprosate (calcium bisacetylhomotaurinate) as a treatment to maintain abstinence in alcohol-dependent patients was assessed for 1 year. Methods: After short-term detoxification, 272 patients participated in a randomized, double-blind, placebo-controlled study. Patients received routine counseling and either the study medication or placebo for 48 weeks; they were followed up for another 48 weeks without medication. Statistical analysis was performed according to the intention-to-treat principle. Results: Patients who were receiving acamprosate showed a significantly higher continuous abstinence rate within the first 60 days of treatment compared with patients who were assigned to placebo treatment (67% vs 50%) until completion of the treatment period (43% vs 21%, log rank P=.005), and they had a significantly longer mean abstinence duration of 224 vs 163 days, or 62% vs 45% days abstinent (P<.001); however, there was no difference in psychiatric symptoms. Of the patients who were receiving acamprosate, 41% had dropped out, whereas 60% of the placebo-treated patients dropped out of the study. Few side effects (mainly diarrhea and headache) were recorded. At the end of a further 48 weeks without receiving study medication, 39% and 17% of the acamprosate- and placebo-treated patients, respectively, had remained abstinent (P=.003). Conclusion: Acamprosate proved to be a safe and effective aid in treating alcohol-dependent patients and in maintaining the abstinence of patients during 2 years. References 1. DiChiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats . Proc Natl Acad Sci U S A . 1988;85:5274-5278.Crossref 2. Engel JA, Enerback C, Fahlke C, Hulthe H, Hard E, Johannssen K, Svensson L, Soderpalm B. Serotonergic and dopaminergic involvement in ethanol intake . In: Naranjo CA, Sellers EM, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1990:68-82. 3. Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current in hippocampal neurons . Science . 1989;243:1721-1724.Crossref 4. Nutt D, Adinoff B, Linnoila M. Benzodiazepines in the treatment of alcoholism . In: Galanter M, ed. Recent Developments in Alcoholism: Treatment Research . New York, NY: Plenum Press; 1989;7:283-313. 5. Fawcett J, Clark DC, Gibbons RD, Aageson CA, Pisani VD, Tilkin JM, Sellers D, Stutzman D. Evaluation of lithium therapy for alcoholism . J Clin Psychiatry . 1984;45:494-499. 6. Jaffe JH, Kranzler HR, Ciraulo DA. Drugs used in the treatment of alcoholism . In: Mendelson JH, Mello NK, eds. Medical Diagnosis and Treatment of Alcoholism . New York, NY: McGraw-Hill International Book Co; 1992:421-461. 7. Sellers EM, Higgins GA, Sobell MB. 5-HT and alcohol abuse . Trends Pharmacol Sci . 1992;13:69-75.Crossref 8. Naranjo CA, Kadlec KE, Sanhueza P, Woodley-Remus D, Sellers EM. Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers . Clin Pharmacol Ther . 1990;47:490-498.Crossref 9. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence: a controlled study . Arch Gen Psychiatry . 1992;49:881-887.Crossref 10. Volpicelli JR, Alterman Al, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence . Arch Gen Psychiatry . 1992;49:876-880.Crossref 11. Boismare F, Daoust M, Moore ND, Saligaut C, Lhuintre JP, Chretien P, Durlach J. A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved? Pharmacol Biochem Behav . 1984;21:787-789.Crossref 12. Le Magnen J, Tran G, Durlach J, Martin C. Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats . Alcohol . 1987;4:103-108.Crossref 13. Knöpfel TH, Zeise ML, Cuenod M, Zieglgänsberger W. L-Homocysteic acid but not L-glutamate is an endogenous N-methyl-D-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro . Neurosci Lett . 1987;81:188-192.Crossref 14. Chabenat C, Chretien P, Daoust M, Moore ND, Andre D, Lhuintre JP, Saligaut C, Boucly P, Boismare F. Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate . Methods Find Exp Clin Pharmacol . 1988;10:311-317. 15. Daoust M, Lhuintre JP, Saligaut C, Moore ND, Flipo JL, Boismare F. Noradrenaline and GABA brain receptors are co-involved in the voluntary intake of ethanol by rats . Alcohol Alcohol . 1987;( (suppl 1) ):319-322. 16. Daoust M, Legrand E, Gewiss M, Heidbreder C, De Witte P, Tran G, Durbin P. Acamprosate modulates synaptosomal GABA transmission in chronically alcoholized rats . Pharmacol Biochem Behav . 1992;41:669-674.Crossref 17. Lhuintre JP, Daoust M, Moore ND, Chretien P, Saligaut C, Tran G, Boismare F, Hillemand B. Ability of calcium di-acetylhomotaurine, a GABA agonist, to prevent relapse in weaned alcoholics . Lancet . 1985;1:1014-1016.Crossref 18. Le Magnen J, Tran G, Durlach J, Martin C. Lack of effects of Ca-acetylhomotaurinate on chronic and acute toxicities of ethanol in rats , Alcohol . 1987;4:103-108.Crossref 19. Zieglgänsberger W, Zeise M. Calcium di-acetylhomotaurinate which prevents relapse in weaned alcoholics decreases the action of excitatory amino acids in neocortical neurons of the rat in vitro . In: Sellers EM, Naranjo CA, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1992:337-341. 20. Zeise M, Kasparow S, Capogna M, Zieglgänsberger W. Acamprosate (calcium homotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors . Eur J Pharmacol . 1993;231:47-52.Crossref 21. Zeise HL, Madamba SG, Siggins GR, Putske J, Zieglgänsberger W. The anticraving substance acamprosate reduces glutamatergic synaptic transmission and a high-threshold calcium current in neocortical and hippocampal neurons . Alcohol Clin Exp Res . 1994;8:2. Abstract. 22. Hillemand B, Lhuintre JP, Steru L, Daoust M, Moore ND. Essai thërapeutique multicentrique du N-bis-acëtylhomotaurinate de calcium (Ca Aota) dans le traitement de l'alcoolo-dëpendent . Rev Alcohol . 1989;34:9-28. 23. Lhuintre JP, Moore ND, Tran G, Steru L, Langrenon S, Daoust M, Parot P, Ladure P, Libert C, Boismare F, Hillemand B. Acamprosate appears to decrease alcohol intake in weaned alcoholics . Alcohol Alcohol . 1990;25:613-622. 24. Pelc I, Le Bon O, Verbanck P, Lehert P, Opsomer L. Calcium-acetylhomotaurinate for maintaining abstinence in weaned alcoholic patients: a placebo-controlled double-blind multicenter study . In: Naranjo CA, Sellers EM, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1992:348-352. 25. Meyer RE. Prospects for a rational pharmacotherapy of alcoholism . J Clin Psychiatry . 1989;50:403-412. 26. Feuerlein W, Ringer C, Küfner H, Antons K. Diagnosis of alcoholism: the Munich Alcoholisms Test (MALT) . In: Galanter M, ed. Currents of Alcoholism . New York, NY: Grune & Stratton; 1980;7:137-147 27. Gillings D, Koch G. The application of the principle of intention to treat to the analysis of clinical trials . Drug Inform J . 1991;25:411-424. 28. Lehert P. Review and discussion of statistical analysis of controlled clinical trials in alcoholism . Alcohol Alcohol . 1993;( (suppl 2) ):157-163. 29. Fuller RK. Assessment of treatment outcome . Alcohol Alcohol . 1991;( (suppl 1) ):519-522. 30. Moos RH, Finney JW, Cronkite RC. Alcoholism Treatment, Context, Process and Outcome . New York, NY: Oxford University Press Inc; 1990. 31. Charness ME. Molecular mechanisms of ethanol intoxification, tolerance, and physical dependence . In: Mendelson JH, Mello NK, eds. Medical Diagnosis and Treatment of Alcoholism . New York, NY: McGraw-Hill International Book Co; 1992:155-199. 32. Samson HH, Harris RA. Neurobiology of alcohol abuse . Trends Pharmacol Sci . 1992;13:206-211.Crossref 33. Ollat H, Parvez H, Parvez S. Alcohol and central neurotransmission . Neurochem Int . 1988;3:275-300.Crossref 34. Littleton JM, Brennan C. Bouchenafa O. The role of calcium flux in the central nervous system actions of ethanol . Ann N Y Acad Sci . 1991;625:388-394.Crossref 35. Hofman PL, Tabakoff B. The role of the NMDA receptor in ethanol withdrawal . In: Jansson B, Jörnvall J, Rydberg U, Terenius L, Vallee BL, eds. Towards a Molecular Basis of Alcohol Use and Abuse . Basel, Switzerland: Birkhäuser Verlag; 1994:61-70. 36. Ballenger JC, Post RM. Kindling as a model for alcohol withdrawal syndromes . Br J Psychiatry . 1978;133:1-4.Crossref 37. Becker HC, Hale RL. Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal 'kindling.' Alcohol Clin Exp Res . 1993;17:94-98.Crossref 38. Grant KA, Valverius P, Hudspith M, Tabakoff B. Ethanol withdrawal seizures and the NMDA-receptor complex . Eur J Pharmacol . 1990;176:289-296.Crossref 39. Zieglgänsberger W, Hauser C, Putzke J, Spanagel R, Wetzel C. The enhanced excitability of central neurons following chronic alcohol intake is reduced by acamprosate . Alcohol Alcohol . 1995;30:C10.22. 40. Littleton J. Acamprosate in alcohol dependence: how does it work? Addiction . 1995;90:1179-1188.Crossref 41. Spanagel R, Zieglgänsberger W, Hundt W. Acamprosate and alcohol, III: effects on alcohol discrimination . Eur J Pharmacol . 1996;305:51-56.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Relapse Prevention by Acamprosate: Results From a Placebo-Controlled Study on Alcohol Dependence

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Publisher
American Medical Association
Copyright
Copyright © 1996 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1996.01830080023006
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Abstract

Abstract Background The effectiveness acamprosate (calcium bisacetylhomotaurinate) as a treatment to maintain abstinence in alcohol-dependent patients was assessed for 1 year. Methods: After short-term detoxification, 272 patients participated in a randomized, double-blind, placebo-controlled study. Patients received routine counseling and either the study medication or placebo for 48 weeks; they were followed up for another 48 weeks without medication. Statistical analysis was performed according to the intention-to-treat principle. Results: Patients who were receiving acamprosate showed a significantly higher continuous abstinence rate within the first 60 days of treatment compared with patients who were assigned to placebo treatment (67% vs 50%) until completion of the treatment period (43% vs 21%, log rank P=.005), and they had a significantly longer mean abstinence duration of 224 vs 163 days, or 62% vs 45% days abstinent (P<.001); however, there was no difference in psychiatric symptoms. Of the patients who were receiving acamprosate, 41% had dropped out, whereas 60% of the placebo-treated patients dropped out of the study. Few side effects (mainly diarrhea and headache) were recorded. At the end of a further 48 weeks without receiving study medication, 39% and 17% of the acamprosate- and placebo-treated patients, respectively, had remained abstinent (P=.003). Conclusion: Acamprosate proved to be a safe and effective aid in treating alcohol-dependent patients and in maintaining the abstinence of patients during 2 years. References 1. DiChiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats . Proc Natl Acad Sci U S A . 1988;85:5274-5278.Crossref 2. Engel JA, Enerback C, Fahlke C, Hulthe H, Hard E, Johannssen K, Svensson L, Soderpalm B. Serotonergic and dopaminergic involvement in ethanol intake . In: Naranjo CA, Sellers EM, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1990:68-82. 3. Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current in hippocampal neurons . Science . 1989;243:1721-1724.Crossref 4. Nutt D, Adinoff B, Linnoila M. Benzodiazepines in the treatment of alcoholism . In: Galanter M, ed. Recent Developments in Alcoholism: Treatment Research . New York, NY: Plenum Press; 1989;7:283-313. 5. Fawcett J, Clark DC, Gibbons RD, Aageson CA, Pisani VD, Tilkin JM, Sellers D, Stutzman D. Evaluation of lithium therapy for alcoholism . J Clin Psychiatry . 1984;45:494-499. 6. Jaffe JH, Kranzler HR, Ciraulo DA. Drugs used in the treatment of alcoholism . In: Mendelson JH, Mello NK, eds. Medical Diagnosis and Treatment of Alcoholism . New York, NY: McGraw-Hill International Book Co; 1992:421-461. 7. Sellers EM, Higgins GA, Sobell MB. 5-HT and alcohol abuse . Trends Pharmacol Sci . 1992;13:69-75.Crossref 8. Naranjo CA, Kadlec KE, Sanhueza P, Woodley-Remus D, Sellers EM. Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers . Clin Pharmacol Ther . 1990;47:490-498.Crossref 9. O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence: a controlled study . Arch Gen Psychiatry . 1992;49:881-887.Crossref 10. Volpicelli JR, Alterman Al, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence . Arch Gen Psychiatry . 1992;49:876-880.Crossref 11. Boismare F, Daoust M, Moore ND, Saligaut C, Lhuintre JP, Chretien P, Durlach J. A homotaurine derivative reduces the voluntary intake of ethanol by rats: are cerebral GABA receptors involved? Pharmacol Biochem Behav . 1984;21:787-789.Crossref 12. Le Magnen J, Tran G, Durlach J, Martin C. Lack of effects of Ca-acetyl homotaurinate on chronic and acute toxicities of ethanol in rats . Alcohol . 1987;4:103-108.Crossref 13. Knöpfel TH, Zeise ML, Cuenod M, Zieglgänsberger W. L-Homocysteic acid but not L-glutamate is an endogenous N-methyl-D-aspartic acid receptor preferring agonist in rat neocortical neurons in vitro . Neurosci Lett . 1987;81:188-192.Crossref 14. Chabenat C, Chretien P, Daoust M, Moore ND, Andre D, Lhuintre JP, Saligaut C, Boucly P, Boismare F. Physicochemical, pharmacological and pharmacokinetic study of a new GABAergic compound, calcium acetylhomotaurinate . Methods Find Exp Clin Pharmacol . 1988;10:311-317. 15. Daoust M, Lhuintre JP, Saligaut C, Moore ND, Flipo JL, Boismare F. Noradrenaline and GABA brain receptors are co-involved in the voluntary intake of ethanol by rats . Alcohol Alcohol . 1987;( (suppl 1) ):319-322. 16. Daoust M, Legrand E, Gewiss M, Heidbreder C, De Witte P, Tran G, Durbin P. Acamprosate modulates synaptosomal GABA transmission in chronically alcoholized rats . Pharmacol Biochem Behav . 1992;41:669-674.Crossref 17. Lhuintre JP, Daoust M, Moore ND, Chretien P, Saligaut C, Tran G, Boismare F, Hillemand B. Ability of calcium di-acetylhomotaurine, a GABA agonist, to prevent relapse in weaned alcoholics . Lancet . 1985;1:1014-1016.Crossref 18. Le Magnen J, Tran G, Durlach J, Martin C. Lack of effects of Ca-acetylhomotaurinate on chronic and acute toxicities of ethanol in rats , Alcohol . 1987;4:103-108.Crossref 19. Zieglgänsberger W, Zeise M. Calcium di-acetylhomotaurinate which prevents relapse in weaned alcoholics decreases the action of excitatory amino acids in neocortical neurons of the rat in vitro . In: Sellers EM, Naranjo CA, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1992:337-341. 20. Zeise M, Kasparow S, Capogna M, Zieglgänsberger W. Acamprosate (calcium homotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors . Eur J Pharmacol . 1993;231:47-52.Crossref 21. Zeise HL, Madamba SG, Siggins GR, Putske J, Zieglgänsberger W. The anticraving substance acamprosate reduces glutamatergic synaptic transmission and a high-threshold calcium current in neocortical and hippocampal neurons . Alcohol Clin Exp Res . 1994;8:2. Abstract. 22. Hillemand B, Lhuintre JP, Steru L, Daoust M, Moore ND. Essai thërapeutique multicentrique du N-bis-acëtylhomotaurinate de calcium (Ca Aota) dans le traitement de l'alcoolo-dëpendent . Rev Alcohol . 1989;34:9-28. 23. Lhuintre JP, Moore ND, Tran G, Steru L, Langrenon S, Daoust M, Parot P, Ladure P, Libert C, Boismare F, Hillemand B. Acamprosate appears to decrease alcohol intake in weaned alcoholics . Alcohol Alcohol . 1990;25:613-622. 24. Pelc I, Le Bon O, Verbanck P, Lehert P, Opsomer L. Calcium-acetylhomotaurinate for maintaining abstinence in weaned alcoholic patients: a placebo-controlled double-blind multicenter study . In: Naranjo CA, Sellers EM, eds. Novel Pharmacological Interventions for Alcoholism . New York, NY: Springer-Verlag NY Inc; 1992:348-352. 25. Meyer RE. Prospects for a rational pharmacotherapy of alcoholism . J Clin Psychiatry . 1989;50:403-412. 26. Feuerlein W, Ringer C, Küfner H, Antons K. Diagnosis of alcoholism: the Munich Alcoholisms Test (MALT) . In: Galanter M, ed. Currents of Alcoholism . New York, NY: Grune & Stratton; 1980;7:137-147 27. Gillings D, Koch G. The application of the principle of intention to treat to the analysis of clinical trials . Drug Inform J . 1991;25:411-424. 28. Lehert P. Review and discussion of statistical analysis of controlled clinical trials in alcoholism . Alcohol Alcohol . 1993;( (suppl 2) ):157-163. 29. Fuller RK. Assessment of treatment outcome . Alcohol Alcohol . 1991;( (suppl 1) ):519-522. 30. Moos RH, Finney JW, Cronkite RC. Alcoholism Treatment, Context, Process and Outcome . New York, NY: Oxford University Press Inc; 1990. 31. Charness ME. Molecular mechanisms of ethanol intoxification, tolerance, and physical dependence . In: Mendelson JH, Mello NK, eds. Medical Diagnosis and Treatment of Alcoholism . New York, NY: McGraw-Hill International Book Co; 1992:155-199. 32. Samson HH, Harris RA. Neurobiology of alcohol abuse . Trends Pharmacol Sci . 1992;13:206-211.Crossref 33. Ollat H, Parvez H, Parvez S. Alcohol and central neurotransmission . Neurochem Int . 1988;3:275-300.Crossref 34. Littleton JM, Brennan C. Bouchenafa O. The role of calcium flux in the central nervous system actions of ethanol . Ann N Y Acad Sci . 1991;625:388-394.Crossref 35. Hofman PL, Tabakoff B. The role of the NMDA receptor in ethanol withdrawal . In: Jansson B, Jörnvall J, Rydberg U, Terenius L, Vallee BL, eds. Towards a Molecular Basis of Alcohol Use and Abuse . Basel, Switzerland: Birkhäuser Verlag; 1994:61-70. 36. Ballenger JC, Post RM. Kindling as a model for alcohol withdrawal syndromes . Br J Psychiatry . 1978;133:1-4.Crossref 37. Becker HC, Hale RL. Repeated episodes of ethanol withdrawal potentiate the severity of subsequent withdrawal seizures: an animal model of alcohol withdrawal 'kindling.' Alcohol Clin Exp Res . 1993;17:94-98.Crossref 38. Grant KA, Valverius P, Hudspith M, Tabakoff B. Ethanol withdrawal seizures and the NMDA-receptor complex . Eur J Pharmacol . 1990;176:289-296.Crossref 39. Zieglgänsberger W, Hauser C, Putzke J, Spanagel R, Wetzel C. The enhanced excitability of central neurons following chronic alcohol intake is reduced by acamprosate . Alcohol Alcohol . 1995;30:C10.22. 40. Littleton J. Acamprosate in alcohol dependence: how does it work? Addiction . 1995;90:1179-1188.Crossref 41. Spanagel R, Zieglgänsberger W, Hundt W. Acamprosate and alcohol, III: effects on alcohol discrimination . Eur J Pharmacol . 1996;305:51-56.Crossref

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Archives of General Psychiatry – American Medical Association

Published: Aug 1, 1996

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