Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T01:56:23.783Z Has data issue: false hasContentIssue false

Acamprosate for the Treatment of Alcohol Dependence: A Review of Double-Blind, Placebo-Controlled Trials

Published online by Cambridge University Press:  07 November 2014

Abstract

Acamprosate (calcium acetyl-homotaurine) is a synthetic compound that crosses the blood-brain barrier and has a chemical structure similar to that of the naturally occurring amino acid neuromediators, homotaurine and γ-aminobu-tyric acid (GABA). Acamprosate appears to act primarily by restoring normal N-methyl-D-aspartate (NMDA) receptor tone in the glutamate system, and has been shown to have a specific dose-dependent effect on decreasing voluntary alcohol intake in animals with no effects on food and water consumption. The safety and efficacy of acamprosate in alcohol-dependent outpatients is currently under evaluation in the United States. Acamprosate has been available by prescription since 1989 in France and more recently in most European and Latin American coutries as well as Australia, South Africa, and Hong Kong. More than 4 million people have been treated with acamprosate since it became commercially available.

The purpose of this article is to review all available double-blind, placebo-controlled clinical trials evaluating the safety and efficacy of acamprosate treatment of alcohol dependence. This work encompasses 16 controlled clinical trials conducted across 11 European countries and involves more than 4,500 outpatients with alcohol dependence. Fourteen of 16 studies found alcohol-dependent patients treated with acamprosate had a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. Additionally, a multinational open-label study of acamprosate in 1,281 patients with alcohol dependence found acamprosate to be equally effective across four major psychosocial concomitant treatment programs in maintaining abstinence and reducing consumption during any periods of relapse. An absence of known strong predictors of response to acamprosate, in conjunction with a modest but consistent effect on prolonging abstinence, and an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol dependence.

Type
Feature Articles
Copyright
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Hunt, WA. Neuroscience research: how has it contributed to our understanding of alcohol abuse and alcoholism? A review. Alcohol Clin Exp Res. 1993;17:10551065.CrossRefGoogle ScholarPubMed
2.Borg, S. Biochemical and clinical features in alcoholic patients during long term abstinence and prior to relapse [abstract]. Alcohol Alcohol. 1988;23:515525.Google Scholar
3.Rassnick, S, D'Amico, E, Riley, E, Pulvirenti, L. GABA and nucleus accumbens glutamate neurotransmission modulate ethanol self-administration in rats. Ann NY Acad Sci. 1992;654:502505Google Scholar
4.Lamblin, F, Deuceuninck, D, DeWitte, PH. Modulation of alcohol preference by NMDA antagonists in male rats. Alcohol Alcohol. 1993;28:639647.Google ScholarPubMed
5.Zeise, ML, Kasparow, S, Capogna, M, Zieglgansberger, W. Acamprosate (calcium homotaurinate) decreases postsynaptic potentials in the rat neocortex: possible involvement of excitatory amino acid receptors. Eur J Pharmacol. 1993;231:4752.CrossRefGoogle Scholar
6.Alquatari, M, Littleton, J. The anticraving drug acamprosate inhibits calcium channel antagonist binding to membranes from the rat cerebral cortex [abstract]. Alcohol Alcohol. 1995;30:551.Google Scholar
7.Naasila, M, Hammoumi, S, Legrand, E, Durbin, P, Daoust, M. Mechanism of action of acamprosate. Part 1. Characterization of spermidine-sensitive acamprosate binding site in rat brain. Alcohol Clin Exp Res. 1998;22:18.Google Scholar
8.Boismare, F, Daoust, M, Moore, N, et al.A homotaurinate derivative reduces the voluntary ethanol intake by rats: are cerebral GABA receptors involved? Pharmacol Biochem Behav. 1984;21:787789.CrossRefGoogle Scholar
9.Le Magnen, J, Tran, G, Durlach, J. Lack of effects of Caacetyl homotaurinate on chronic and acute toxicities of ethanol in rats. Alcohol. 1987;4:103108.CrossRefGoogle ScholarPubMed
10.Gewiss, M, Heidbreder, CH, Opsomer, L, Durbin, PH, DeWitte, PH. Acamprosate and diazepam differentially modulate alcohol-induced behavioural and cortical alterations in rats following chronic inhalation of ethanol vapour. Alcohol Alcohol. 1991;26:129137.CrossRefGoogle ScholarPubMed
11.Grant, KA, Woolverton, WL. Reinforcing and discriminative effects of acetylhomotaurine in animals. Pharmacol Biochem Behav. 1989;32:607611.CrossRefGoogle Scholar
12.Durbin, P, Hulot, T, Chabac, S. Pharmacodynamics and pharmacokinetics of acamprosate: an overview. In: Soyka, M, ed. Acamprosate in Relapse Prevention of Alcoholism. Berlin, Germany: Springer Verlag; 1996.Google Scholar
13.Mason, BH, Goodman, AM. Cognitive effects of naltrexone and acamprosate administered alone and in combination. Presented at: Annual Meeting of the Research Society on Alcoholism (RSA); [June 27-July 1, 1999] 1999; Santa Barbara, Calif.Google Scholar
14.Wilde, MI, Wagstaff, AJ. Acamprosate: a review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification. Drugs. 1997;53:10381053.CrossRefGoogle ScholarPubMed
15.Lhuintre, JP, Daoust, M, Moore, ND, et al.Ability of calcium acetyl homotaurine, a GABA agonist, to prevent relapse in weaned alcoholics. Lancet. 1985;1:10141016.CrossRefGoogle ScholarPubMed
16.Lhuintre, JP, Moore, ND, Tran, G, et al.Acamprosate appears to decrease alcohol intake in weaned alcoholics. Alcohol Alcohol. 1990;25:613622.CrossRefGoogle ScholarPubMed
17.Pelc, I, Le Bon, O, Verbanck, P, Lehert, PH, Opsomer, L. Calcium acetyl homotaurinate for maintaining abstinence in weaned alcoholic patients; a placebo controlled double-blind multicentre study. In: Naranjo, C, Sellers, E, eds. Novel Pharmacological Interventions for Alcoholism. New York, NY: Springer Verlag; 1992:348352.CrossRefGoogle Scholar
18.Ladewig, D, Knecht, T, Lehert, P, et al.Acamprosate - a stabilizing factor in the long-term treatment of alcoholics. Ther Umsch. 1993;50:182188.Google Scholar
19.Whitworth, A, Fischer, F, Lesch, OM, et al.Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996;347:14381442.CrossRefGoogle ScholarPubMed
20.Barrias, JA, Chabac, S, Ferreira, L, Fonte, A, Potgieter, AS, Teixeira de Sousa E. Acamprosate: multicenter Portuguese efficacy and tolerance evaluation study. Psiquiatria Clinica 1997;18:149160.Google Scholar
21.Poldrugo, F. Acamprosate treatment in a long-term community-based alcohol rehabilitation programme. Addiction. 1997;92:15371546.CrossRefGoogle Scholar
22.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;22:573579.CrossRefGoogle ScholarPubMed
23.Rousseaux, JP, Hers, D, Ferauge, M. Does acamprosate diminish the appetite for alcohol in weaned alcoholics? J Pharm Belg. 1996;51:6568.Google Scholar
24.Sass, H, Soyka, M, Mann, K, Zieglgansberger, W. Relapse prevention by acamprosate: results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiatry. 1996;53:673680.CrossRefGoogle Scholar
25.Geerlings, PJ, Ansoms, C, van den Brink, W. Acamprosate and prevention of relapse in alcoholics. European Addiction Research. 1997;3:129137.CrossRefGoogle Scholar
26.Paille, F, Guelfi, JD, Perkins, AC, Royer, RJ, Stem, L, Parot, P. Double-blind randomized multicentre trial of acamprosate in maintaining abstinence from alcohol. Alcohol Alcohol. 1995;30:239247.Google ScholarPubMed
27.Pelc, I, Verbanck, P, Le Bon, O, Gavrilovic, M, Lion, K, Lehert, P. Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependence patients: a 90-day placebo-controlled dose-finding study. Br J Psychiatry. 1997;171:7377.CrossRefGoogle ScholarPubMed
28.Chick, J, Howlett, H, Morgan, MY, Ritson, B. United Kingdom multicentre acamprosate study (UKMAS): a 6 month prospective study of acamprosate vs placebo in preventing relapse after withdrawal from alcohol. Alcohol Alcohol. In press.Google Scholar
29.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. In press.Google Scholar
30.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Washington, DC: American Psychiatric Association; 1987.Google Scholar
31.Mason, BJ, Goodman, AM, Koob, GF. Methodology of the US multicenter study of acamprosate in alcohol dependence. Presented at the American College of Neuropsychopharmacology (ACNP) Annual Meeting, Kamuela, Hawaii. 1997.Google Scholar
32.Mason, BJ, Goodman, AM. Brief Intervention and Medication Compliance Procedures Therapist's Manual. New York, NY: Lipha Pharmaceuticals, Inc.; 1997.Google Scholar