Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: The role of patient motivation

The Pearson Center for Alcoholism and Addiction Research and Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, TPC-5, La Jolla, CA 92037, United States.
Journal of Psychiatric Research (Impact Factor: 4.09). 09/2006; 40(5):383-93. DOI: 10.1016/j.jpsychires.2006.02.002
Source: PubMed

ABSTRACT This is the first US study to evaluate the clinical efficacy of acamprosate (Campral), a newly FDA-approved medication for maintaining abstinence in patients with alcohol dependence following alcohol withdrawal. We compared effects of the standard 2 g dose (n=258) and an exploratory 3 g dose of acamprosate (n=83) versus placebo (n=260), and evaluated drug safety in a double-blind, placebo-controlled 6-month trial conducted in 21 outpatient clinics across the US. Participants were 601 volunteers with current alcohol dependence recruited primarily by advertisement. All patients concomitantly received eight sessions of brief manual-guided counseling ( The main outcome measure was the percentage of alcohol-free days over the 6-month study. Self-report was validated by breath alcohol concentration, gamma-glutamyltransferase (GGT) and collateral informant interviews. The percentage of abstinent days did not differ significantly across groups in a priori analysis (54.3% for placebo, 56.1% for 2 g, 60.7% for 3 g). Post-hoc analysis controlling for baseline variables and treatment exposure found acamprosate was associated with a significantly higher percentage of abstinent days than placebo (52.3% for placebo, 58.2% for 2 g, 62.7% for 3 g; P=0.01), with an even greater effect in the subgroup of 241 patients having a baseline goal of abstinence (58.1% for placebo, 70.0% for 2 g, 72.5% for 3 g; P=0.02). There were no deaths or serious drug-related adverse events. The US study findings suggest that acamprosate is safe and well tolerated in a broadly inclusive sample of alcoholics and appears effective in populations of patients motivated to have a treatment goal of abstinence.

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    • "Glial sodium dependent transporters , GLAST ( EAAT1 ) and GLT1 ( EAAT2 ) , in particular GLT1 , are responsible for at least 90% of extracellular glutamate removal ( For review , see Anderson and Swanson , 2000 ) . Impaired glu - tamate uptake due to dysfunction or downregulation of EAAT2 results in several neurological disorders , including Amyotrophic Lateral Sclerosis ( ALS ) , Alzheimer ' s disease , epilepsy , ischemia and hepatic encephalopathy ( Maragakis and Rothstein , 2006 ) . Importantly , we have previously demonstrated that chronic exposure to alcohol results in significant down - regulation of GLT1 expression in the Acb and / or PFC in P rats ( Sari and Sreemantula , 2012 ; Sari et al . "
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    Frontiers in Neuroscience 04/2015; 9:144. DOI:10.3389/fnins.2015.00144 · 3.70 Impact Factor
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    • "There is some supporting evidence, since Morley et al. (2010) (Ib) reported an interaction between dependence severity and acamprosate treatment, such that higher levels of dependence severity at baseline predicted a beneficial response to acamprosate. In addition, failure of the two US trials to find acamprosate effective would fit with this hypothesis, since participants were less severely dependent (COMBINE, Anton et al., 2006; Mason et al., 2006) (Ib). However, evidence from meta-analyses has not been found in support of this (NICE, 2011a; Verheul et al., 2005) (Ia). "
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    • "However, dosing by body weight is no longer recommended and 1998 mg per day is the approved standard fixed dose. Two trials (Anton, 2006 and Mason, 2006 in a small experimental group) used a dose of 3,000 mg which represents a 0.5 fold increase over the approved therapeutic dose. In keeping with the standard approach to meta-analysis, treatment conditions are collapsed to active drug versus placebo groups. "
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