Predictors of acamprosate efficacy: Results from a pooled analysis of seven European trials including 1485 alcohol-dependent patients
ABSTRACT Acamprosate is a proven effective intervention in the treatment of alcohol dependence. However, acamprosate prevents lapses or relapses only in a minority of patients. An important question, therefore, is whether there is a specific subgroup of patients who respond particularly well to acamprosate.
To identify predictors of acamprosate efficacy. Based upon the available evidence and hypotheses about the mechanisms underlying acamprosate's effects on drinking behavior, the following variables were considered to be potential positive predictors: high physiological dependence at baseline, negative family history of alcoholism, late age-of-onset, serious anxiety symptomatology at baseline, severe craving at baseline, and female gender.
Potential predictors of acamprosate's efficacy were analyzed in a pooled analysis of data from seven randomized placebo-controlled trials involving a total of 1485 patients with alcohol dependence. Outcome is measured in terms of cumulative abstinence duration (CAD), continuous abstinence (ABST), and time to first relapse (TFR).
CAD and ABST were predicted by baseline measures of craving and anxiety, as well as by study and treatment condition. Acamprosate efficacy was not differentially associated with any of the predictor variables. Importantly, the hypotheses were rejected despite the large sample size and sufficient statistical power.
The most straight-forward clinical implication of this study is that acamprosate can be considered as a potentially effective pharmacotherapy for all patients with alcohol dependence. The effect size of acamprosate alone is, however, moderate. Some evidence indicates that the combination of acamprosate with naltrexone or disulfiram leads to substantially better outcomes.
Full-textDOI: · Available from: Roel Verheul, Jul 28, 2015
- SourceAvailable from: David J Nutt
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- "However, evidence from meta-analyses has not been found in support of this (NICE, 2011a; Verheul et al., 2005) (Ia). Verheul et al. (2005) (Ia) indeed concluded that acamprosate is potentially effective for anyone with alcohol dependence. At the time of writing these guidelines, a large prospective study set up to define if there are any subgroups who respond to either acamprosate or naltrexone, 'project PREDICT' has yet to formally publish its results (Mann et al., 2009) (Ib). "
ABSTRACT: The British Association for Psychopharmacology guidelines for the treatment of substance abuse, harmful use, addiction and comorbidity with psychiatric disorders primarily focus on their pharmacological management. They are based explicitly on the available evidence and presented as recommendations to aid clinical decision making for practitioners alongside a detailed review of the evidence. A consensus meeting, involving experts in the treatment of these disorders, reviewed key areas and considered the strength of the evidence and clinical implications. The guidelines were drawn up after feedback from participants. The guidelines primarily cover the pharmacological management of withdrawal, short- and long-term substitution, maintenance of abstinence and prevention of complications, where appropriate, for substance abuse or harmful use or addiction as well management in pregnancy, comorbidity with psychiatric disorders and in younger and older people.Journal of Psychopharmacology 05/2012; 26(7):899-952. DOI:10.1177/0269881112444324 · 2.81 Impact Factor
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- "ACAMP has also been found to be preferentially effective in alcohol-dependent subjects that obtained low scores on somatic distress (Kiefer et al., 2005). However, Verheul et al. (2005) in a pooled analysis of seven European trials including 1485 patients found that ACAMP was not differentially associated with any predictor variables including physiological dependence, familial alcoholism, age-of-onset, anxiety symptomatology, severity of craving or gender. Another pooled analysis of European trials (Sass et al., 1995) similarly failed to find any predictors of efficacious response to ACAMP on any baseline characteristics. "
ABSTRACT: To assess which baseline characteristics of patients predict response to treatment with acamprosate (ACAMP) and naltrexone (NTX) in alcohol dependence. Outcome data from a 12-week randomized controlled trial of NTX, ACAMP and placebo for alcohol dependence were analysed by multiple logistic regression analyses to determine the predictive effects of gender and the baseline measures of dependence severity, craving, depression, anxiety and readiness to change in addition to NTX and ACAMP treatment. Moderators of the effect of each medication on outcomes were also examined. Relapse was predicted by the interaction terms of ACAMP and alcohol dependence severity, NTX and depression as well as NTX and the readiness to change measure Taking Steps. Abstinence was similarly predicted by the interaction term ACAMP and alcohol dependence severity. The efficacy of NTX and ACAMP in reducing relapse or lapse is influenced by different clinical characteristics.Alcohol and Alcoholism 10/2010; 45(6):520-6. DOI:10.1093/alcalc/agq068 · 2.09 Impact Factor
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- "Withdrawal from chronic alcohol exposure causes long-term alterations in numerous behavioral outcomes. While several of these alterations are believed to contribute significantly to treatment efficacy in human alcoholics, withdrawal-related anxiety makes a significant contribution to relapse in humans (Cohn et al., 2003; Linnoila, 1989; Lucht et al., 2002; Verheul et al., 2005). The neurophysiological mechanisms governing these long-term changes in anxiety-related behaviors are not well understood. "
ABSTRACT: Withdrawal (WD) anxiety is a significant factor contributing to continued alcohol abuse in alcoholics. This anxiety is extensive, long-lasting, and develops well after the obvious physical symptoms of acute WD. The neurobiological mechanisms underlying this prolonged WD-induced anxiety are not well understood. The basolateral amygdala (BLA) is a major emotional center in the brain and regulates the expression of anxiety. New evidence suggests that increased glutamatergic function in the BLA may contribute to WD-related anxiety following chronic ethanol exposure. Recent evidence also suggests that kainate-type ionotropic glutamate receptors are inhibited by intoxicating concentrations of acute ethanol. This acute sensitivity suggests potential (KA-R) contributions by these receptors to the increased glutamatergic function seen during chronic exposure. Therefore, we examined the effect of chronic intermittent ethanol (CIE) and WD on KA-R-mediated synaptic transmission in the BLA of Sprague-Dawley rats. Our study showed that CIE, but not WD, increased synaptic responses mediated by KA-Rs. Interestingly, both CIE and WD occluded KA-R-mediated synaptic plasticity. Finally, we found that BLA field excitatory postsynaptic potential responses were increased during CIE and WD via a mechanism that is independent of glutamate release from presynaptic terminals. Taken together, these data suggest that KA-Rs might contribute to postsynaptic increases in glutamatergic synaptic transmission during CIE and that the mechanisms responsible for the expression of KA-R-dependent synaptic plasticity might be engaged by chronic ethanol exposure and WD.Alcohol (Fayetteville, N.Y.) 03/2009; 43(1):25-33. DOI:10.1016/j.alcohol.2008.11.002 · 2.04 Impact Factor