Naltrexone Acamprosate

GABRB2 Y-Aminobutyric acid (1-2 rs3219151 (C+1412T) Alcohol Acamprosate, naltrexone... 

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. 

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... 

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 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... 

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... 

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. 

Acamprosate-treated patients (999 to 1,998 mg/day and higher) have less craving and more success in maintaining abstinence than placebo-treated patients. The combination of acamprosate and naltrexone with psychosocial intervention may be more effective than acamprosate alone. 

The common side effects of naltrexone are nansea, headache, and dizziness. In addition, naltrexone has the potential for toxic effects on the liver and should not be used in an alcoholic with cirrhosis or other known liver disease. Because it blocks opiate receptors, patients treated with naltrexone are unable to benefit from the analgesic effects of opiates such as codeine or morphine. Naltrexone may increase serum levels of acamprosate in patients taking both medications. 

The obvions qnestion is whether combining naltrexone, acamprosate, and/or disnlfiram is better than either medication alone. To our knowledge, this has not been systematically studied, but it may be a viable alternative in particularly severe cases when other treatment options have failed. The cornerstone of success in the treatment of alcoholism is clearly the behavioral intervention including Alcoholics Anonymons. 

Three drugs—disulfiram, naltrexone, and acamprosate—have FDA approval for adjunctive treatment of alcohol dependence. 

To review the pharmacology of alcohol, and agents to reduce alcohol consumption including acamprosate and naltrexone. 

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%). 

Kranzler and Van Kirk s (2001) review revealed. similar results for acamprosate. As we noted earlier, this medication also has received FDA approval tor use in the United States and is used and studied w idely in the rest of the world. The studies of acamprosate to date show, like naltrexone, modest effectiveness overall and inconsistency in findings from different studies. A large clinical trial of acamprosate is currently in progress in the United States. 

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