Acamprosate

Lovinger DM (2000) Examination of ethanol spermine and acamprosate actions on native and recombinant NMDA receptors. Alcohol Clin Exp Res 24 183A... 

C1H9NO 156-87-6) see Acamprosate calcium Cyclophosphamide Dexpanthenol Domperidone Gusperimus trihydrochloride Mefenorex Urapidil 7-amino-3-[(Z)-l-propenyl]-3-cephem-4-carboxylic acid (CiqHi2N203S 106447-44-3) see ci s-Cefprozil 3-aminopropionaIdehyde diethyl acetal (C7H,7N02 41365-75-7) see Atorvastatin calcium P-aminopropionic acid phosphite (C3H, N0 P) see Pamidronic acid... 

There is also a growing number of studies in which naltrexone has been compared or combined with acamprosate. Kiefer et al. (2003) randomly as-... 

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. 

Kranzler and Van Kirk (2001) included 11 acamprosate studies in a metaanalysis involving more than 3,000 subjects. The magnitude of the advantage shown by acamprosate over placebo in those studies varied as a function of the outcomes examined, which included the percentage of patients who were abstinent throughout the study, cumulative abstinent days, and the rate of study retention, all of which favored the active medication. Acamprosate yielded outcomes that were, on average, 7%—13% better than those shown by individuals who received placebo. 

A recent meta-analysis of total abstinence as an outcome in clinical trials of acamprosate (Mann et al. 2004) included 17 studies and a total of more than 4,000 patients. The authors found a significant advantage for acampro-... 

Chick et al. (2003) conducted a meta-analysis that included data from 15 studies of acamprosate in an effort to determine whether acamprosate reduces the severity of relapse for patients in abstinence-oriented treatment who fail to abstain completely. Among patients who relapsed to drinking, acamprosate was significantly associated with less quantity and frequency of drinking, compared with placebo, at each of four follow-up periods (i.e., at 30, 90, 180, and 360 treatment days). During each of these periods, there were also fewer acamprosate-treated patients who drank an average of five or more drinks per day. 

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. 

In summary, studies involving more than 4,000 patients provided consistent evidence of a beneficial effect of acamprosate in relapse prevention. On the basis of the drug s efficacy (as demonstrated by at least a doubling of the total abstinence rate in three European studies, two of which were of 12 months duration) and a good safety profile, the FDA approved the medica-... 

Summary. Currently, the most promising agents that directly reduce alcohol consumption are the opioid antagonists and acamprosate. Further re-... 

Besson J, Aeby F, Kasas A, et al Combined efficacy of acamprosate and disulfiram in the treatment of alcoholism a controlled study. Alcohol Clin Exp Res 22 373-579, 1998... 

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... 

Chick J, Lehert P, Landron F, et al Does acamprosate improve reduction of drinking as well as aiding abstinence J Psychopharmacol 17 397-A02, 2003 Chrostek L, Jelski W, Szmitkowski M, et al Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans. J Clin Lab Anal 17 93-96, 2003... 

Kranzler HR, Van Kirk J Efficacy of naltrexone and acamprosate for alcoholism treatment a meta-analysis. Alcohol Clin Exp Res 23 1335-1341, 2001 Kranzler HR, Babor TF, Lauerman R Problems associated with average alcohol consumption and frequency of intoxication in a medical population. Alcohol Clin Exp Res 14 119-126, 1990... 

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

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... 

Mason B, Goodman A Acamprosate new preclinical and clinical research. Presented at the 23rd Annual Scientific Meeting of the Research Society on Alcoholism, Denver, CO, June 24—29, 2000... 

Rubio G, Jimenez-Arriero MA, Ponce G, et al Naltrexone versus acamprosate one year follow-up of alcohol dependence treatment. Alcohol Alcohol 36 419 25,... 

Kranzler HR, Van Kirk J Efficacy of naltrexone and acamprosate for alcoholism treatment a meta-analysis. Alcohol Clin Exp Res 23 1335-1341, 2001... 

Koob GF, Mason BJ, De Witte P, et al Potential neuroprotective effects of acamprosate. Alcohol Clin Exp Res 26 386—592, 2002... 

Higgins ST, Sigmon SC, Wong CJ, et al Community reinforcement therapy for cocaine-dependent outpatients. Arch Gen Psychiatry 60 1043—1052, 2003 Hopkins JS, Garbutt JC, Poole CL, et al Naltrexone and acamprosate meta-analysis of two medical treatments for alcoholism. Presented at the 25th annual meeting of the Research Society on Alcoholism, San Francisco, CA, June 28—July 3, 2002... 

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. 

The therapeutic dose of acamprosate is 666 mg orally three times daily, and it is supplied as a 333 mg tablet. It can be started at the full dose in most patients without titration. It differs from disulfiram and naltrexone in that it is excreted by the kidneys without liver metabolism. Consequently, it is contraindicated in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/minute), and dose reduction is necessary when the creatinine clearance is between 30 and 50 mL/minute. The most common side effects are gastrointestinal and include nausea and diarrhea. Rates of suicidal thoughts were also increased in patients treated for 1 year with acamprosate (2.4%) versus placebo (0.8%). If necessary the total daily dose maybe decreased by 1 to 3 tablets (333-999 mg) per day to alleviate side effects. 

Naltrexone can increase blood levels of acamprosate by increasing its absorption, but the clinical significance of this is not known. 

Disulfiram (250 mg per day) can be used to promote abstinence from alcohol. Acamprosate and naltrexone can be used to decrease craving for alcohol, but they are not likely to result in complete abstinence from alcohol use. 

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