Combined Acamprosate and Naltrexone, With Cognitive Behavioural Therapy Is Superior to Either Medication Alone for Alcohol Abstinence: A Single Centres' Experience With Pharmacotherapy

Feeney, Gerald F.X.; Connor, Jason P.; Young, Ross McD.; Tucker, Jim B.; McPherson, Andrew

doi:10.1093/alcalc/agl007

Cited by 78 publications

(41 citation statements)

References 18 publications

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“…Concerning the combined treatment with both compounds, 3 trials have been published so far. Two of them (Feeney et al, 2006;Kiefer et al, 2003) found an additive effect if both drugs were combined, indicating that there might be a synergistic effect. Alternatively, a differential effect could be assumed.…”

Section: A Prospective Approach To Predict Response To Acamprosatementioning

confidence: 99%

Acamprosate: Recent Findings and Future Research Directions

Mann

Kiefer

Spanagel

et al. 2008

Alcoholism Clin & Exp Res

147

111

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This article explores the mechanisms of action and the potential responder profile of acamprosate, a compound efficacious in relapse prevention of alcoholism. New evidence at the molecular and cellular level suggests that acamprosate attenuates hyper-glutamatergic states that occur during early abstinence and involves iono (NMDA)- and metabotrotropic (mGluR5) glutamate receptors along with augmented intracellular calcium release and electrophysiological changes. Thus mutant mice with enhanced glutamate levels exhibit higher alcohol consumption than wild type mice and respond better to acamprosate, demonstrating that acamprosate acts mainly on a hyper-glutamatergic system. This mode of action further suggests that acamprosate exhibits neuroprotective properties. In rats, cue-induced reinstatement behavior is significantly reduced by acamprosate treatment whereas cue-induced craving responses in alcohol-dependent patients seem not to be affected by this treatment. An ongoing study ("Project Predict") defines specific responder profiles for an individualized use of acamprosate and naltrexone. Neurophysiological as well as psychometric data are used to define 2 groups of patients: "reward cravers" and "relief cravers". While naltrexone should work better in the first group, acamprosate is hypothesized to be efficacious in the latter where withdrawal associated and/or cue induced hyper-glutamatergic states are thought to trigger relapse. Further research should target the definition of subgroups applying endophenotypic approaches, e.g. by detecting a hyperglutamatergic syndrome using MR spectroscopy.

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Section: A Prospective Approach To Predict Response To Acamprosatementioning

confidence: 99%

Acamprosate: Recent Findings and Future Research Directions

Mann

Kiefer

Spanagel

et al. 2008

Alcoholism Clin & Exp Res

147

111

View full text Add to dashboard Cite

show abstract

“…3. There is good evidence supporting adjunctive pharmacotherapy for alcohol, nicotine, and heroin dependence (Feeney, Connor, Young, Tucker, & McPherson, 2006;Hettema & Hendricks, 2010;Ling, Hillhouse, Ang, Jenkins, & Fahey, 2013). 4.…”

Section: Assessmentmentioning

confidence: 99%

A clinician's quick guide of evidence‐based approaches: Substance use disorders

Gullo

Connor

Kavanagh

2015

Clinical Psychologist

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“…Another large study (over 580 subjects, treated for 6 months) in the United Kingdom failed to find a difference between the treatment effects of acamprosate and placebo [101], but intervention commenced 25 days after recovery from physical withdrawal symptoms, a substantially large latency compared to the other studies [19]. A meta-analysis of these studies and others [18,102–105] concluded a significant benefit for acamprosate treatment as assessed 6 months after the start of treatment [106]. A more recent analysis of the clinical data, where the effect of treatment in male and female subjects were analyzed separately, confirmed this conclusion and reported no sex differences in the beneficial effects of acamprosate [107].…”

Section: Clinical Developmentmentioning

confidence: 99%

The development of acamprosate as a treatment against alcohol relapse

Kufahl

Watterson

2014

Expert Opinion on Drug Discovery

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Introduction Globally, alcohol abuse and dependence are significant contributors to chronic disease and injury and are responsible for nearly 4% of all deaths annually. Acamprosate (Campral), one of only three pharmacological treatments approved for the treatment of alcohol dependence, has shown mixed efficacy in clinical trials in maintaining abstinence of detoxified alcoholics since studies began in the 1980’s. Yielding inconsistent results, these studies have prompted skepticism. Areas Covered Herein, the authors review the preclinical studies which have assessed the efficacy of acamprosate in various animal models of alcohol dependence and discuss the disparate findings from the major clinical trials. Moreover, the authors discuss the major limitations of these preclinical and clinical studies and offer explanations for the often contradictory findings. The article also looks at the importance of the calcium moiety that accompanies the salt form of acamprosate and its relevance to its activity. Expert opinion The recent discovery that large doses of calcium largely duplicate the effects of acamprosate in animal models has introduced a serious challenge to the widely-held functional association between this drug and the glutamate neurotransmission system. Future research on acamprosate or newer pharmacotherapeutics should consider assessing plasma and/or brain levels of calcium as a correlate or mediating factor in anti-relapse efficacy. Furthermore, preclinical research on acamprosate has thus far lacked animal models of chemical dependence on alcohol, and the testing of rodents with histories of alcohol intoxication and withdrawal is suggested.

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Combined Acamprosate and Naltrexone, With Cognitive Behavioural Therapy Is Superior to Either Medication Alone for Alcohol Abstinence: A Single Centres' Experience With Pharmacotherapy

Abstract: The addition of both medications (naltrexone and acamprosate) resulted in measurable benefit and was well tolerated. In this patient population naltrexone with CBT is as effective as combined medication with CBT, but the trend favours combination medication.

Cited by 78 publications

References 18 publications

Acamprosate: Recent Findings and Future Research Directions

Acamprosate: Recent Findings and Future Research Directions

A clinician's quick guide of evidence‐based approaches: Substance use disorders

The development of acamprosate as a treatment against alcohol relapse

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