Acamprosate for the treatment of alcohol dependence.

Background: Both inpatient and outpatient treatment centers that focus solely on psychosocial therapies for the treatment of alcohol dependence have high relapse rates. Thus, extensive research has focused on the development of pharmacologic moieties to attenuate the craving for alcohol after acute alcohol detoxification. Three drug therapies are currently approved by the US Food and Drug Administration (FDA) for this purpose: disulfiram, naltrexone, and acamprosate. The latter was approved by the FDA in 2004.

Objective: This article describes the pharmacologic properties and clinical usefulness of acamprosate for the treatment of alcohol dependence.

Methods: Relevant information was identified through searches of MEDLINE (1966 to March 2005), International Pharmaceutical Abstracts (1970-2005), Current Contents (1996-2005), and Cumulative Index to Nursing and Allied Health Literature (1982-Week 2, 2004) using the key words acamprosate, alcohol dependence, and alcoholism (MeSH).

Results: Acamprosate limited to randomized, controlled clinical trials yielded 33 hits in MEDLINE. Twenty-two articles were reviewed for efficacy end points, and 10 were reviewed for pharmacology and pharmacokinetics data. Acamprosate plus pharmacokinetics and pharmacodynamics yielded 19 hits, some of which were duplicates from the previously described search. Acamprosate plus meta-analysis (MeSH) yielded 5 hits, naltrexone plus meta-analysis (MeSH) yielded 9 hits, and disulfiram plus meta-analysis yielded 3 hits. The most recent review articles and their reference lists were assessed to ensure completeness of literature searches. Based on these searches, acamprosate is known to be an analogue of taurine and gamma-aminobutyric acid (GABA), 2 central nervous system neuromodulators. Acamprosate is thought to share some of the cellular actions of taurine affecting GABA and glutaminergic receptors in the nucleus accumbens, a brain region that may be responsible for the reinforcing effects received after alcohol consumption. Acamprosate is thought to also suppress excitation-induced calcium entry that results from chronic alcohol exposure, thereby altering the conformation of the N-methyl-d-aspartate receptors. The percentage of patients taking acamprosate who were completely abstinent throughout the different durations of the studies varied from approximately 18% to 61%, compared with 4% to 45% with placebo. Diarrhea was the most common adverse effect accompanying acamprosate therapy, and this was generally described as dose related and transient.

Conclusions: Acamprosate is associated with modest treatment effects. Its efficacy is similar to naltrexone, and the combination of acamprosate and naltrexone appears to be more efficacious than acamprosate alone, when combined with psychosocial interventions.