Acamprosate, in alcohol dependence

Littleton] Acamprosate in alcohol dependence how does it work Addiction 90 1179-1188, 1995... 

Ooteman W, Naassila M, Koeter MW, Verheul R, Schippers GM, Houchi H, Daoust M, van den Brink W (2009) Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol 14 328-337... 

Littleton J, Zieglgansberger W Pharmacological mechanisms of naltrexone and acamprosate in the prevention of relapse in alcohol dependence. Am J Addict 12 (suppl 1) S3-S11,2003... 

Mann K, Lehert P, Morgan MY The efficacy of acamprosate in the maintenance of abstinence in alcohol-dependent individuals results of a meta-analysis. Alcohol... 

Acamprosate is indicated for the maintenance of abstinence in alcohol-dependent adults. It appears to decrease brain hyperexcitability during alcohol withdrawal, which may reduce alcohol consumption. Treatment should be initiated as soon as possible after the alcohol-withdrawal period is complete. The recommended period of treatment with acamprosate is one year and treatment should be combined with counselling. The GGT level can be monitored as a marker of abstinence from alcohol. 

Kiefer F, Witt SH, Frank J, Richter A, Treutlein J, Lemenager T, Nothen MM, Cichon S, Batra A, Berner M, Wodarz N, Zimmermann US, Spanagel R, Wiedemann K, Smolka MN, Heinz A, Rietschel M, Mann K (2011) Involvement of the atrial natriuretic peptide transcription factor GATA4 in alcohol dependence, relapse risk and treatment response to acamprosate. Pharmacogenomics J 11 368-374... 

Acamprosate has effects on drinking behavior that are related to modulation of glutamatergic transmission. In particular, acamprosate depresses the elevated glutamatergic transmission and NMDA receptor activation that occur in alcohol dependence and withdrawal. The effect of acamprosate appears to be most effective in decreasing alcohol consumption and prolonging abstinence. This drug remains the most widely validated treatment medication for the treatment of alcoholism. 

In a study in 24 healthy subjects, the concurrent use of naltrexone 50 mg daily and acamprosate 2 g daily for 7 days modestly increased the rate and extent of absorption of acamprosate, as indicated by a 33% inerease in maximum level, a 33% reduction in time to maximum level, and a 25% increase in AUC. There was no change in naltrexone pharmaeokinetics. Similarly, an increase in acamprosate levels was seen in a study of the use of acamprosate and naltrexone in alcohol-dependent subjeets." No particular adverse events were identified on concurrent use, " suggesting that the drugs may be used together. 

Johnson BA, O Malley SS, Ciraulo DA, Roache JD, Chambers RA, 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, 281-93. 

Acamprosate. Acamprosate (calcium acetylhomotaurinate), an amino acid derivative, affects both GABA and excitatory amino acid (i.e., glutamate) neurotransmission (the latter effect most likely being the one that is important for its therapeutic effects in alcoholism). Initially evaluated in a singlecenter trial in France, acamprosate was shown to be twice as effective as placebo in reducing the rate at which alcoholic patients returned to drinking (Lhuin-tre et al. 1985). The safety and efficacy of the medication have been studied most widely in Europe, and three of these studies provided the basis for the recent approval of acamprosate by the FDA for clinical use in the United States. As with naltrexone, there exist a number of meta-analytic studies that provide consistent evidence of the efficacy of the medication in the treatment of alcohol dependence. 

Verheul et al. (2004) pooled data from seven European acamprosate studies in an effort to identify patient-related predictors of response to the medication. Although they examined a number of potential predictors, including patients level of physiological dependence before treatment, family history of alcoholism, age of onset of alcoholism, baseline anxiety symptom severity, baseline craving, and gender, none was shown to interact with acamprosate treatment. These findings led the authors to conclude that, although the effect size for acamprosate was moderate, the medication can be considered potentially effective for all patients with alcohol dependence. 

Bouza C, Magro A, Munoz A, et al Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence a systematic review. Addiction 99 811-828, 2004... 

Currently the three FDA-approved medications that are indicated to treat alcohol dependence are disulfiram, naltrexone, and acamprosate. Both disulfiram and acamprosate are indicated in patients who have already achieved initial abstinence. Only naltrexone may be initiated without regard to abstinence status. 

Tempesta E et al. Acamprosate and relapse prevention in the treatment of alcohol dependence a placebo-controlled study. Alcohol 2000 35(2) 202—209. 

For maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation. Treatment with acamprosate should be part of a comprehensive management program that includes psychosocial support. 

Results from animal studies indicating a decrease in voluntary alcohol intake led to a number of double-blind, placebo-controlled trials involving more than 4,500 patients with alcohol dependence (424). In a review of these data. Mason and Ownby (424) found that 14 of 16 studies demonstrated a significantly superior benefit from acamprosate versus placebo in terms of the following ... 

Acamprosate (calcium acetylhomotaurinate) has been postulated to act by restoring the alcohol-induced neurotransmission imbalance of inhibition-excitation inputs believed to underlie alcohol dependence (1,2). The molecular structure of acamprosate explains its specificity toward the basic molecular mechanisms involved in the pathophysiology of alcohol dependence. A competitive interaction has been described between spermidine and acamprosate, suggesting a specific binding site for acamprosate on A-methyl-D-aspartate receptors (3). 

In an open, single-blind, randomized study, naltrexone (50 mg/day) and acamprosate (1665-1998 mg/day) were used for 1 year by 157 recently detoxified alcohol-dependent men with moderate dependence (4). The time to first relapse was 63 days (naltrexone) and 42 days (acamprosate) after 1 year, 41% of those given naltrexone and 17% of those given acamprosate had not relapsed. Adverse effects were more common with naltrexone and were worse during the first 2 weeks of treatment. They included nausea (25 versus 4%), abdominal pain (23 versus 4%), drowsiness (35 versus 2%), headache (13 versus 6%), and nasal congestion (23 versus 7%). 

Currently, disulfiram, naltrexone, and acamprosate are currently the only treatments approved for the management of alcohol dependence. Studies in animals have demonstrated that a diet enriched in vitamin E and saturated fatty acids reduces alcoholic liver injury by decreasing hpid per-oxidation. " Liver transplantation is the treatment of choice in end-stage liver disease. The results of transplantation in alcoholic liver disease are comparable to those with other forms of hver disease. ... 

A. Soyka M, Chick J, Use of acamprosate and opioid antagonists in the treatment of alcohol dependence ... 

Mason BJ, Heyser CJ (2010) Acamprosate a prototypic neuromodulator in the treatment of alcohol dependence. CNS Neurol Disord Drug Targets 9 23-32... 

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