Acamprosate: A prototypic neuromodulator in the treatment of alcohol dependence

CNS and Neurological Disorders - Drug Targets

Volumn 9, Issue 1, 2010, Pages 23-32

  Mason, Barbara J ^a   Heyser, Charles J ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b FRANKLIN AND MARSHALL COLLEGE   (United States)

Author keywords

Acamprosate; Alcohol dependence; Alcoholism; Campral; Treatment

Indexed keywords

ACAMPROSATE; NALTREXONE; PLACEBO;

ALCOHOLISM; CLINICAL TRIAL; DIARRHEA; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG EXCRETION; DRUG FORMULATION; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENTIATION; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG WITHDRAWAL; GENOTOXICITY; HUMAN; MAXIMUM PLASMA CONCENTRATION; NEUROBIOLOGY; NEUROIMAGING; NEUROMODULATION; NEUROPROTECTION; NONHUMAN; REVIEW; SINGLE DRUG DOSE; SLEEP PATTERN; TREATMENT INDICATION; TREATMENT OUTCOME;

EID: 77949881369     PISSN: 18715273     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152710790966641     Document Type: Review

References (122)

1. Mason, B.J. Treatment of alcohol-dependent outpatients with acamprosate: a clinical review. J. Clin. Psychiatry, 2001, 62(Suppl 20), 42-48.
2. Mark, T.L.; Kassed, C.A.; Vandivort-Warren, R.; Levit, K.R.; Kranzler, H.R. Alcohol and opioid dependence medications: prescription trends, overall and by physician specialty. Drug Alcohol Depend., 2009, 99, 345-349.
3. th ed. American Psychiatric Press: Washington DC, 1994.
4. Koob, G.F.; Le Moal, M. Neurobiology of Addiction. Academic Press: London, 2006.
5. De Witte, P.; Littleton, J.; Parot, P.; Koob G. Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action. CNS Drugs, 2005, 19, 517-537.
6. Littleton, J. Acamprosate in alcohol dependence: how does it work? Addiction, 1995, 90, 1179-1188.
7. Chabenat, C.; Ladure, P.; Moore, N.; Boucly, P.; Boismare, F. Application of an analytical method to calcium acetylhomotaurinate determination in urine. Arzneimittelforschung, 1989, 39, 1413-1414.
8. Girault, J.; Gobin, P.; Fourtillan, J.B. Determination of calcium acetylhomotaurinate in human plasma and urine by combined gas chromatography-negative-ion chemical ionization mass spectrometry. J. Chromatogr., 1990, 530, 295-305.
9. Saivin, S.; Hulot, T.; Chabac, S.; Potgieter, A.; Durbin, P.; Houin, G. Clinical pharmacokinetics of acamprosate. Clin. Pharmacokinet., 1998, 35, 331-345.
10. Wilde, M.I.; Wagstaff, A.J. Acamprosate: a review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification. Drugs, 1997, 53, 1038-1053.
11. Durbin, P.; Hulot, T.; Chabac, S. Pharmacodynamics and pharmacokinetics of acamprosate: an overview. In: Soyka, M., Ed.; Acamprosate in Relapse Prevention of Alcoholism. Proceedings of the 1st Campral Symposium. Springer: Stuttgart, Germany, 1995, pp. 47-64.
12. Campral [package insert]. Forest Pharmaceuticals, Inc.: Saint Louis, MO, 2005.
13. Mason, B.J. Rationale for combining acamprosate and naltrexone for treating alcohol dependence. J. Stud. Alcohol. Suppl., 2005, 15, 148-156.
14. Johnson, B.A.; O'Malley, S.S.; Ciraulo, D.A.; Roache, J.D.; Chambers, R.A.; Sarid-Segal, O.; Couper, D. Dose-ranging kinetics and behavioral pharmacology of naltrexone and acamprosate, both alone and combined, in alcohol-dependent subjects. J. Clin. Psychopharmacol., 2003, 23, 281-293.
15. Gessa, G.L.; Muntoni, F.; Collu, M.; Vargiu, L.; Mereu, G. Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res., 1985, 348, 201-203.
16. Brodie, M.S.; Shefner, S.A.; Dunwiddie, T.V. Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res., 1990, 508, 65-69.
17. Diana, M.; Pistis, M.; Muntoni, A.; Rossetti, Z.L.; Gessa, G. Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats. Eur. J. Pharmacol., 1992, 221, 403-404.
18. Diana, M.; Pistis, M.; Muntoni, A., Gessa, G. Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: evidence of protracted abstinence. Neuroscience, 1996, 71, 411-415.
19. Shen, R.Y.; Chiodo, L.A. Acute withdrawal after repeated ethanol treatment reduces the number of spontaneously active dopaminergic neurons in the ventral tegmental area. Brain Res., 1993, 622, 289-293.
20. Bailey, C.P.; Manley, S.J.; Watson, W.P.; Wonnacott, S.; Molleman, A.; Little, H.J. Chronic ethanol administration alters activity in ventral tegmental area neurons after cessation of withdrawal hyperexcitability. Brain Res., 1998, 803, 144-152.
21. Lima-Landman, M.T.; Albuquerque, E.X. Ethanol potentiates and blocks NMDA-activated single-channel currents in rat hippocampal pyramidal cells. FEBS Lett., 1989, 247, 61-67.
22. Lovinger, D.M.; White, G.; Weight, F.F. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science, 1989, 243, 1721-1724.
23. Nie, Z.; Madamba, S.G.; Siggins, G.R. Ethanol inhibits glutamatergic neurotransmission in nucleus accumbens neurons by multiple mechanisms. J. Pharmacol. Exp. Ther., 1994, 271, 1566-1573.
24. Simson, P.E.; Criswell, H.E.; Johnson, K.B.; Hicks, R.E.; Breese, G.R. Ethanol inhibits NMDA-evoked electrophysiological activity in vivo. J. Pharmacol. Exp. Ther., 1991, 257, 225-231.
25. Carta, M.; Ariwodola, O.J.; Weiner, J.L.; Valenzuela, C.F. Alcohol potently inhibits the kainate receptor-dependent excitatory drive of hippocampal interneurons. Proc. Natl. Acad. Sci. USA, 2003, 100, 6813-6818.
26. Engberg, G.; Hajós, M. Alcohol withdrawal reaction as a result of adaptive changes of excitatory amino acid receptors. Naunyn Schmied. Arch. Pharmacol., 1992, 346, 437-441.
27. Chandler, L.J.; Newsom, H.; Sumners, C.; Crews, F. Chronic ethanol exposure potentiates NMDA excitotoxicity in cerebral cortical neurons. J. Neurochem., 1993, 60, 1578-1581.
28. Snell, L.D.; Tabakoff, B.; Hoffman, P.L. Radioligand binding to the N-methyl-D-aspartate receptor/ionophore complex: alterations by ethanol in vitro and by chronic in vivo ethanol ingestion. Brain Res., 1993, 602, 91-98.
29. Hoffman, P.L.; Tabakoff, B. The role of the NMDA receptor in ethanol withdrawal. EXS, 1994, 71, 61-70.
30. Davidson, M.; Shanley, B.; Wilce, P. Increased NMDA-induced excitability during ethanol withdrawal: a behavioural and histological study. Brain Res., 1995, 674, 91-96.
31. Ripley, T.L.; Little, H.J. Ethanol withdrawal hyperexcitability in vitro is selectively decreased by a competitive NMDA receptor antagonist. Brain Res., 1995, 699, 1-11.
32. Stephens, D.N. A glutamatergic hypothesis of drug dependence: extrapolations from benzodiazepine receptor ligands. Behav. Pharmacol., 1995, 6, 425-446.
33. Mehta, A.K.; Ticku, M.K. Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels. J. Pharmacol. Exp. Ther., 1988, 246, 558-564.
34. Suzdak, P.D.; Schwartz, R.D.; Skolnick, P.; Paul, S.M. Alcohols stimulate gamma-aminobutyric acid receptor-mediated chloride uptake in brain vesicles: correlation with intoxication potency. Brain Res., 1988, 444, 340-345.
35. B receptors. Alcohol. Clin. Exp. Res., 1991, 15, 233-237.
36. A receptor alpha subunits reveal that chronic alcohol treatment down-regulates alpha-subunit expression in rat brain regions. J. Neurochem., 1993, 61, 1620-1625.
37. - uptake in cerebral cortical synaptoneurosomes. J. Pharmacol. Exp. Ther., 1988, 246, 158-164.
38. Leslie, S.W.; Barr, E.; Chandler, J.; Farrar, R.P. Inhibition of fast- and slow-phase depolarization-dependent synaptosomal calcium uptake by ethanol. J. Pharmacol. Exp. Ther., 1983, 225, 571-575.
39. 2+ in brain cells. Alcohol, 1992, 9, 63-69.
40. Messing, R.O.; Carpenter, C.L.; Diamond, I.; Greenberg, D.A. Ethanol regulates calcium channels in clonal neural cells. Proc. Natl. Acad. Sci. USA, 1986, 83, 6213-6215.
41. Dolin, S.; Little, H.; Hudspith, M.; Pagonis, C.; Littleton, J. Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology, 1987, 26, 275-279.
42. Dahchour, A.; De Witte, P. Ethanol and amino acids in the central nervous system: assessment of the pharmacological actions of acamprosate. Prog. Neurobiol., 2000, 60, 343-362.
43. Naassila, M.; Hammoumi, S.; Legrand, E.; Durbin, P.; Daoust, M. Mechanism of action of acamprosate. Part I: characterization of spermidine-sensitive acamprosate binding site in rat brain. Alcohol. Clin. Exp. Res., 1998, 22, 802-809.
44. al Qatari, M.; Bouchenafa, O.; Littleton, J. Mechanism of action of acamprosate. Part II: ethanol dependence modifies effects of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex. Alcohol. Clin. Exp. Res., 1998, 22, 810-814.
45. Zeise, M.L.; Kasparov, S.; Capogna, M.; Zieglgänsberger, W. Acamprosate (calcium acetylhomotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. Eur. J. Pharmacol., 1993, 231, 47-52.
46. Grant, K.A.; Valverius, P.; Hudspith, M.; Tabakoff, B. Ethanol withdrawal seizures and the NMDA receptor complex. Eur. J. Pharmacol., 1990, 176, 289-296.
47. Tsai, G.; Coyle, J.T. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annu. Rev. Med., 1998, 49, 173-184.
48. Tsai, G.E.; Ragan, P.; Chang, R.; Chen, S.; Linnoila, V.M.; Coyle, J.T. Increased glutamatergic neurotransmission and oxidative stress after alcohol withdrawal. Am. J. Psychiatry, 1998, 155, 726-732.
49. Dahchour, A.; De Witte, P.; Bolo, N.; Nédélec, J.F.; Muzet, M.; Durbin, P.; Macher, J.P. Central effects of acamprosate: part 1. Acamprosate blocks the glutamate increase in the nucleus accumbens microdialysate in ethanol withdrawn rats. Psychiatry Res., 1998, 82, 107-114.
50. Popp, R.L.; Lovinger, D.M. Interaction of acamprosate with ethanol and spermine on NMDA receptors in primary cultured neurons. Eur. J. Pharmacol., 2000, 394, 221-231.
51. Staner, L.; Boeijinga, P.; Danel, T.; Gendre, I.; Muzet, M.; Landron, F.; Luthringer, R. Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects. Alcohol. Clin. Exp. Res., 2006, 30, 1492-1499.
52. Engelhard, K.; Werner, C.; Lu, H.; Möllenberg, O.; Zieglgänsberger, W.; Kochs, E. The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia: a study with the lipid peroxidase inhibitor U-101033E. Anaesthesist, 2000, 49, 816-821.
53. al Qatari, M.; Khan, S.; Harris, B.; Littleton, J. Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain. Alcohol. Clin. Exp. Res., 2001, 25, 1276-1283.
54. Mayer, S.; Harris, B.; Gibson, D.A.; Blanchard, J.; Prendergast, M.A.; Holley, R.C.; Littleton, J. Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced by spermidine or by changing the medium in organotypic hippocampal slice cultures from rat. Alcohol. Clin. Exp. Res., 2002, 26, 655-662.
55. Koob, G.F.; Mason, B.J.; De Witte, P.; Littleton, J.; Siggins, G.R. Potential neuroprotective effects of acamprosate. Alcohol. Clin. Exp. Res., 2002, 26, 586-592.
56. Adde-Michel, C.; Hennebert, O.; Laudenbach, V.; Marret, S.; Leroux, P. Effect of acamprosate on neonatal excitotoxic cortical lesions in in utero alcohol-exposed hamsters. Neurosci. Lett., 2005, 374, 109-112.
57. Littleton, J.M. Acamprosate in alcohol dependence: implications of a unique mechanism of action. J. Addict. Med., 2007, 1, 115-125.
58. Davidson, M.; Wilce, P. Chronic ethanol treatment leads to increased ornithine decarboxylase activity: implications for a role of polyamines in ethanol dependence and withdrawal. Alcohol. Clin. Exp. Res., 1998, 22, 1205-1211.
59. Hu, X.J.; Ticku, M.K. Chronic ethanol treatment upregulates the NMDA receptor function and binding in mammalian cortical neurons. Brain Res. Mol. Brain Res., 1995, 30, 347-356.
60. Hu, X.J.; Follesa, P.; Ticku, M.K. Chronic ethanol treatment produces a selective upregulation of the NMDA receptor subunit gene expression in mammalian cultured cortical neurons. Brain Res. Mol. Brain Res., 1996, 36, 211-218.
61. Harris, B.R.; Gibson, D.A.; Prendergast, M.A.; Blanchard, J.A.; Holley, R.C.; Hart, S.R.; Scotland, R.L.; Foster, T.C.; Pedigo, N.W.; Littleton, J.M. The neurotoxicity induced by ethanol withdrawal in mature organotypic hippocampal slices might involve cross-talk between metabotropic glutamate type 5 receptors and N-methyl-D-aspartate receptors. Alcohol. Clin. Exp. Res., 2003, 27, 1724-1735.
62. Boismare, F.; Daoust, M.; Moore, N.; Saligaut, C.; Lhuintre, J.P.; 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.
63. Le Magnen, J.; Tran, G.; Durlach, J.; Martin, C. Dose-dependent suppression of the high alcohol intake of chronically intoxicated rats by Ca-acetyl homotaurinate. Alcohol, 1987, 4, 97-102.
64. Spanagel, R.; Hölter, S.M.; Allingham, K.; Landgraf, R.; Zieglgänsberger, W. Acamprosate and alcohol: I: effects on alcohol intake following alcohol deprivation in the rat. Eur. J. Pharmacol., 1996, 305, 39-44.
65. Heyser, C.J.; Schulteis, G.; Durbin, P.; Koob, G.F. Chronic acamprosate eliminates the alcohol deprivation effect while having limited effects on baseline responding for ethanol in rats. Neuropsychopharmacology, 1998, 18, 125-133.
66. Stromberg, M.F.; Mackler, S.A.; Volpicelli, J.R.; O'Brien, C.P. Effect of acamprosate and naltrexone, alone or in combination, on ethanol consumption. Alcohol, 2001, 23, 109-116.
67. Gupta, T.; Syed, Y.M.; Revis, A.A.; Miller, S.A.; Martinez, M.; Cohn, K.A.; Demeyer, M.R.; Patel, K.Y.; Brzezinska, W.J.; Rhodes, J.S. Acute effects of acamprosate and MPEP on ethanol Drinking-in-the-Dark in male C57BL/6J mice. Alcohol. Clin. Exp. Res., 2008, 32, 1992-1998.
68. Simms, J.A.; Steensland, P.; Medina, B.; Abernathy, K.E.; Chandler, L.J.; Wise, R.; Bartlett, S.E. Intermittent access to 20% ethanol induces high ethanol consumption in Long-Evans and Wistar rats. Alcohol. Clin. Exp. Res., 2008, 32, 1816-1823.
69. Dahchour, A.; De Witte, P. Acamprosate decreases the hypermotility during repeated ethanol withdrawal. Alcohol, 1999, 18, 77-81.
70. Cole, J.C.; Littleton, J.M.; Little, H.J. Acamprosate, but not naltrexone, inhibits conditioned abstinence behaviour associated with repeated ethanol administration and exposure to a plus-maze. Psychopharmacology (Berl.), 2000, 147, 403-411.
71. Farook, J.M.; Krazem, A.; Lewis, B.; Morrell, D.J.; Littleton, J.M.; Barron, S. Acamprosate attenuates the handling induced convulsions during alcohol withdrawal in Swiss Webster mice. Physiol. Behav., 2008, 95, 267-270.
72. Kotlinska, J.; Bochenski, M. The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats. Eur. J. Pharmacol., 2008, 598, 57-63.
73. Bachteler, D.; Economidou, D.; Danysz, W.; Ciccocioppo, R.; Spanagel, R. The effects of acamprosate and neramexane on cue- induced reinstatement of ethanol-seeking behavior in rat. Neuropsychopharmacology, 2005, 30, 1104-1110.
74. Spanagel, R.; Putzke, J.; Stefferl, A.; Schöbitz, B.; Zieglgänsberger, W. Acamprosate and alcohol: II. Effects on alcohol withdrawal in the rat. Eur. J. Pharmacol., 1996, 305, 45-50.
75. Rosenthal, R.N.; Gage, A.; Perhach, J.L.; Goodman, A.M. Acamprosate: safety and tolerability in the treatment of alcohol dependence. J. Addict. Med., 2008, 2, 40-50.
76. Paille, F.M.; Guelfi, J.D.; Perkins, A.C.; Royer, R.J.; Steru, L.; Parot, P. Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol. Alcohol Alcohol., 1995, 30, 239-247.
77. Pelc, I.; Verbanck, P.; Le Bon, O.; Gavrilovic, M.; Lion, K.; Lehert, P. Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients. A 90-day placebo-controlled dose-finding study. Br. J. Psychiatry, 1997, 171, 73-77.
78. Mason, B.J. Acamprosate. Recent Dev. Alcohol., 2003, 16, 203-215.
79. Schneider, U.; Wohlfarth, K.; Schulze-Bonhage, A.; Haacker, T.; Müller-Vahl, K.R.; Zedler, M.; Becker, H.; Dengler, R.; Emrich, H.M. Effects of acamprosate on memory in healthy young subjects. J. Stud. Alcohol, 1999, 60, 172-175.
80. Mason, B.J.; Goodman, A.M.; Dixon, R.M.; Hameed, M.H.; Hulot, T.; Wesnes, K.; Hunter, J.A.; Boyeson, M.G. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology, 2002, 27, 596-606.
81. Gross, M.M.; Goodenough, D.R.; Hastey, J.; Lewis, E. Experimental study of sleep in chronic alcoholics before, during, and after four days of heavy drinking with a nondrinking comparison. Ann. NY Acad. Sci., 1973, 215, 254-265.
82. Gross, M.M.; Hastey, J.M. Slow wave sleep and carry-over of functional tolerance and physical dependence in alcoholics. Adv. Exp. Med. Biol., 1975, 59, 477-493.
83. Williams, H.L.; Rundell, O.H.; Jr. Altered sleep physiology in chronic alcoholics: reversal with abstinence. Alcohol. Clin. Exp. Res., 1981, 5, 318-325.
84. Adamson, J.; Burdick, J.A. Sleep of dry alcoholics. Arch. Gen. Psychiatry, 1973, 28, 146-149.
85. Brower, K.J.; Aldrich, M.S.; Robinson, E.A.; Zucker, R.A.; Greden, J.F. Insomnia, self-medication, and relapse to alcoholism. Am. J. Psychiatry, 2001, 158, 399-404.
86. Koob, G.F. The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction, 2006, 101 Suppl 1, 23-30.
87. Goldstein, R.Z.; Volkow, N.D. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry, 2002, 159, 1642-1652.
88. Bolo, N.; Nédélec, J.F.; Muzet, M.; De Witte, P.; Dahchour, A.; Durbin, P.; Macher, J.P. Central effects of acamprosate: part 2. Acamprosate modifies the brain in-vivo proton magnetic resonance spectrum in healthy young male volunteers. Psychiatry Res., 1998, 82, 115-1127.
89. Boeijinga, P.H.; Parot, P.; Soufflet, L.; Landron, F.; Danel, T.; Gendre, I.; Muzet, M.; Demazières, A.; Luthringer, R. Pharmacodynamic effects of acamprosate on markers of cerebral function in alcohol-dependent subjects administered as pretreatment and during alcohol abstinence. Neuropsychobiology, 2004, 50, 71-77.
90. Sass, H.; Soyka, M.; Mann, K.; Zieglgänsberger, W. Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence. Arch. Gen. Psychiatry, 1996, 53, 673-680.
91. Lhuintre, J.P.; Daoust, M.; Moore, N.D.; Chretien, P.; Saligaut, C.; Tran, G.; Bosimare, F.; Hillemand, B. Ability of calcium bis acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics. Lancet, 1985, 1, 1014-1016.
92. Lhuintre, J.P.; Moore, N.; 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.
93. Pelc, I.; Le Bon, O.; Verbanck, P.; Lehert, P.H.; Opsomer, L. Calcium acetyl homotaurinate for maintaining abstinence in weaned alcoholic patients: a placebo-controlled double-blind multicentre study. In: Naranjo, C.A.; Sellers, E.M.; Eds.; Novel Pharmacological Interventions for Alcoholism, Springer Verlag: New York, NY, 1992, pp. 348-352.
94. Ladewig, D.; Knecht, T.; Lehert, P.; Fendl, A. Acamprosate - a stabilizing factor in long-term withdrawal of alcoholic patients. Ther. Umsch., 1993, 50, 182-188.
95. Roussaux, J.P.; Hers, D.; Ferauge, M. Does acamprosate diminish the appetite for alcohol in weaned alcoholics?. J. Pharm. Belg., 1996, 51, 65-68.
96. Whitworth, A.B.; Fischer, F.; Lesch, O.M.; Nimmerrichter, A.; Oberbauer, H.; Platz, T.; Potgieter, A.; Walter, H.; Fleischhacker, W.W. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet, 1996, 347, 1438-1442.
97. Barrias, J.A.; Chabac, S.; Ferreira, L.; Fonte, A.; Potgieter, A.S.; Teixeira de Sousa, E. Acamprosate: multicenter Portuguese efficacy and tolerance evaluation study. Psiquiatria Clin., 1997, 18, 149-160.
98. Geerlings, P.J.; Ansoms, C.; van den Brink, W. Acamprosate and prevention of relapse in alcoholics. Eur. Addict. Res., 1997, 3, 129-137.
99. Poldrugo, F. Acamprosate treatment in a long-term community-based alcohol rehabilitation programme. Addiction, 1997, 92, 1537-1546.
100. 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.
101. Chick, J.; Howlett, H.; Morgan, M.Y., Ritson, B. United Kingdom Multicentre Acamprosate Study (UKMAS): a 6-month prospective study of acamprosate versus placebo in preventing relapse after withdrawal from alcohol. Alcohol Alcohol., 2000, 35, 176-187.
102. Tempesta, E.; Janiri, L.; Bignamini, A.; Chabac, S.; Potgieter, A. Acamprosate and relapse prevention in the treatment of alcohol dependence: a placebo-controlled study. Alcohol Alcohol., 2000, 35, 202-209.
103. Gual, A.; Lehert, P. Acamprosate during and after acute alcohol withdrawal: a double-blind placebo-controlled study in Spain. Alcohol Alcohol., 2001, 36, 413-418.
104. Kiefer, F.; Jahn, H.; Tarnaske, T.; Helwig, H.; Briken, P.; Holzbach, R.; Kämpf, P.; Stracke, R.; Baehr, M.; Naber, D.; Wiedemann, K. Comparing and combining naltrexone and acamprosate in relapse prevention of alcoholism: a double-blind, placebo-controlled study. Arch. Gen. Psychiatry, 2003, 60, 92-99.
105. Namkoong, K.; Lee, B.O.; Lee, P.G.; Choi, M.J.; Lee, E. Acamprosate in Korean alcohol-dependent patients: a multi-centre, randomized, double-blind, placebo-controlled study. Alcohol Alcohol., 2003, 38, 135-141.
106. Niederhofer, H.; Staffen, W. Acamprosate and its efficacy in treating alcohol dependent adolescents. Eur. Child Adolesc. Psychiatry, 2003, 12, 144-148.
107. Baltieri, D.A.; De Andrade, A.G. Acamprosate in alcohol dependence: a randomized controlled efficacy study in a standard clinical setting. J. Stud. Alcohol, 2004, 65, 136-139.
108. Anton, R.F.; O'Malley, S.S.; Ciraulo, D.A.; Cisler, R.A.; Couper, D.; Donovan, D.M.; Gastfriend, D.R.; Hosking, J.D.; Johnson, B.A.; LoCastro, J.S.; Longabaugh, R.; Mason, B.J.; Mattson, M.E.; Miller, W.R.; Pettinati, H.M.; Randall, C.L.; Swift, R.; Weiss, R.D.; Williams, L.D.; Zweben, A.; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA, 2006, 295, 2003-2017.
109. Mason, B.J.; Goodman, A.M.; Chabac, S.; Lehert, P. Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation. J. Psychiatr. Res., 2006, 40, 383-393.
110. Morley, K.C.; Teesson, M.; Reid, S.C.; Sannibale, C.; Thomson, C.; Phung, N.; Weltman, M.; Bell, J.R.; Richardson, K.; Haber, P.S. Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. Addiction, 2006, 101, 1451-1462.
111. 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, 51-63.
112. Kranzler, H.R.; Van Kirk, J. Efficacy of naltrexone and acamprosate for alcoholism treatment: a meta-analysis. Alcohol. Clin. Exp. Res., 2001, 25, 1335-1341.
113. Rösner, S.; Leucht, S.; Lehert, P.; Soyka, M. Acamprosate supports abstinence, naltrexone prevents excessive drinking: evidence from a meta-analysis with unreported outcomes. J. Psychopharmacol., 2008, 22, 11-23.
114. Bouza, C.; Angeles, M.; Munoz, A.; Amate, J.M. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction, 2004, 99, 811-828.
115. Dranitsaris, G.; Selby, P.; Negrete, J.C. Meta-analyses of placebo-controlled trials of acamprosate for the treatment of alcohol dependence: impact of the combined pharmacotherapies and behavior interventions study. J. Addict. Med., 2009, 3, 74-82.
116. Ooteman, W.; Naassila, M.; Koeter, M.W.; Verheul, R.; Schippers, G.M.; Houchi, H.; Daoust, M.; van den Brink, W. Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict. Biol., 2009, 14, 328-337.
117. Mason, B.J.; Crean, R. Acamprosate in the treatment of alcohol dependence: clinical and economic considerations. Expert Rev. Neurother., 2007, 7, 1465-1477.
118. Schädlich, P.K.; Brecht, J.G. The cost effectiveness of acamprosate in the treatment of alcoholism in Germany. Economic evaluation of the Prevention of Relapse with Acamprosate in the Management of Alcoholism (PRAMA) Study. Pharmacoeconomics, 1998, 13, 719-730.
119. Palmer, A.J.; Neeser, K.; Weiss, C.; Brandt, A.; Comte, S.; Fox, M. The long-term cost-effectiveness of improving alcohol abstinence with adjuvant acamprosate. Alcohol Alcohol., 2000, 35, 478-492.
120. Annemans, L.; Vanoverbeke, N.; Tecco, J.; D'Hooghe, D. Economic evaluation of Campral (Acamprosate) compared to placebo in maintaining abstinence in alcohol-dependent patients. Eur. Addict. Res., 2000, 6, 71-78.
121. Rychlik, R.; Siedentop, H.; Pfeil, T.; Daniel, D. Cost-effectiveness of adjuvant treatment with acamprosate in maintaining abstinence in alcohol dependent patients. Eur. Addict. Res., 2003, 9, 59-64.
122. Koob, G.F.; Lloyd, G.K.; Mason, B.J. Development of pharmacotherapies for drug addiction: a Rosetta stone approach. Nat. Rev. Drug. Discov., 2009, 8, 500-515.