Acamprosate for alcohol dependence

Rösner, Susanne; Hackl-Herrwerth, Andrea; Leucht, Stefan; Lehert, Philippe; Vecchi, Simona; Soyka, Michael

doi:10.1590/s1516-31802010000600014

Cited by 77 publications

(119 citation statements)

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“…We have simulated the potential effects of five different interventions: pharmacological treatment (based on the Cochrane reviews: (Rösner et al, 2010b;Rösner et al, 2010a) be an increase in pharmacological treatment, with brief interventions in hospitals being almost at the same level. If 20% of people with AD were treated, we estimated that 1.1% of all female alcohol-attributable deaths and 3.2% of all male alcohol-attributable deaths could be prevented within one year 2 .…”

Section: Effects Of Potential Treatment Interventionsmentioning

confidence: 99%

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Consumo de alcohol, dependencia alcohólica, trastornos relacionados con el alcohol en España. Impacto de los tratamientos de la dependencia alcohólica

Rehm

Shield

et al. 2013

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Resumen AbstractAlcohol consumption in Spain has traditionally followed the Mediterranean drinking pattern, featuring daily drinking with meals, beer as the preferred beverage, and comparatively little drinking to intoxication. Alcohol dependence (AD), one of the most detrimental disorders caused by alcohol, was prevalent in 0.2% of women and 1.2% of men, corresponding to 31,200 women and 186,000 men in Spain with AD in 2005 in the age group of 15 to 64 year. These prevalence estimates of alcohol dependence are likely underestimated due to limitations in the World Mental Health Survey which cannot be fully corrected for; however, the estimates of AD for Spain represent the most accurate and up to date estimates available. Alcohol creates a significant health burden in Spain with 11.3 premature deaths in women per 100,000 aged 15 to 64 years, and 40.9 premature deaths in men per 100,000 in the same age group were due to alcohol consumption (data for 2004). This amounts to 8.4% of all female deaths and 12.3% of all the male deaths in this age group being attributable to alcohol consumption. A large percentage of these harms were due to heavy alcohol consumption and AD. AD is undertreated in Spain, with less than 10% of all people with AD treated. For those who are treated, psychotherapy is the most utilized form of treatment to avoid relapse. If 40% of AD patients in Spain were treated with pharmacological treatment (the most effective treatment method), 2.2% of female and 6.2% of male deaths due to AD would be prevented within one year. Thus by increasing treatment rates is an important means of reducing the alcohol-attributable mortality and health burden in Spain.Key Words: Alcohol, dependence, mortality, treatment, Spain.El consumo de alcohol en España ha seguido tradicionalmente los patrones mediterráneos: consumo diario en las comidas, preferentemente cerveza y comparativamente poco consumo dirigido a la intoxicación. La dependencia alcohólica (AD), una de las enfermedades más deteriorantes provocadas por el alcohol, tiene una prevalencia del 0.2% en mujeres y del 1.2% en hombres, lo que significa que unas 31,200 mujeres y 186,000 hombres en España padecían AD en 2005 en el grupo etario comprendido entre 15 y 64 años. Estas prevalencias son probablemente estimaciones a la baja, debidas básicamente a limitaciones en el World Mental Health Survey que no son susceptibles de ser corregidas. Sin embargo, dichas estimaciones son las mas actualizadas y fiables en la actualidad. El alcohol genera importantes costes para la salud en España: 11.3 muertes prematuras por 100.000 en mujeres entre 15 y 64 años, y 40.9 muertes prematuras por 100.000 hombres en el mismo grupo etario fueron debidas al consumo de alcohol (datos del 2004). Ello significa que el 8.4% de todas las muertes en mujeres y el 12.3% en varones de este grupo etario son atribuibles al alcohol. Un elevado porcentaje de estas muertes fueron debidas al consumo muy elevado de alcohol y a la AD. La AD está infratratada en España. Menos del 10% de los afectad...

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Section: Effects Of Potential Treatment Interventionsmentioning

confidence: 99%

“…Pooled estimates of (Rösner et al, 2010b;Rösner et al, 2010a). For this simulation we are concerned with the differences in consumption between baseline and follow-up in the group receiving medications only.…”

Section: Infectious and Parasitic Diseasesmentioning

confidence: 99%

Consumo de alcohol, dependencia alcohólica, trastornos relacionados con el alcohol en España. Impacto de los tratamientos de la dependencia alcohólica

Rehm

Shield

et al. 2013

Adicciones

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“…Acamprosate is a safe and welltolerated drug that does not affect craving (Umhau et al, 2011) but the risk to relapse. In a recent Cochrane Review Rösner et al (2010) summarized 24 randomized controlled trials (RCTs) on acamprosate, and concluded that acamprosate significantly reduces the risk of any drinking with a relative risk (RR) of 0.86. A RR of 1 means that there is no difference between placebo and treatment, whereas a RRo1 means that relapse occurs less frequently in the treatment group.…”

Section: Introductionmentioning

confidence: 99%

Acamprosate Produces Its Anti-Relapse Effects Via Calcium

Spanagel

Vengeliene

Jandeleit³

et al. 2013

Neuropsychopharmacol

126

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Alcoholism is one of the most prevalent neuropsychiatric diseases, having an enormous health and socioeconomic impact. Along with a few other medications, acamprosate (Campral-calcium-bis (N-acetylhomotaurinate)) is clinically used in many countries for relapse prevention. Although there is accumulated evidence suggesting that acamprosate interferes with the glutamate system, the molecular mode of action still remains undefined. Here we show that acamprosate does not interact with proposed glutamate receptor mechanisms. In particular, acamprosate does not interact with NMDA receptors or metabotropic glutamate receptor group I. In three different preclinical animal models of either excessive alcohol drinking, alcohol-seeking, or relapse-like drinking behavior, we demonstrate that N-acetylhomotaurinate by itself is not an active psychotropic molecule. Hence, the sodium salt of N-acetylhomotaurinate (i) is ineffective in alcohol-preferring rats to reduce operant responding for ethanol, (ii) is ineffective in alcohol-seeking rats in a cue-induced reinstatement paradigm, (iii) and is ineffective in rats with an alcohol deprivation effect. Surprisingly, calcium salts produce acamprosatelike effects in all three animal models. We conclude that calcium is the active moiety of acamprosate. Indeed, when translating these findings to the human situation, we found that patients with high plasma calcium levels due to acamprosate treatment showed better primary efficacy parameters such as time to relapse and cumulative abstinence. We conclude that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of acamprosate described in more than 450 published original investigations and clinical trials and 1.5 million treated patients can possibly be attributed to calcium.

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“…The logic is as follows: if calcium is the active moiety of acamprosate, and acamprosate does not produce a positive treatment effect in a randomized controlled trial, how then should calcium be associated with treatment outcome? Second, the now presented re-evaluation of the PREDICT data based on 76 acamprosate-and 25 placebo-treated patients with available plasma calcium levels was underpowered to detect any treatment effect (Rösner et al, 2010).Mann and colleagues bring up also two other points of criticism: they state 'While Spanagel et al (2014) used systemic application others have shown that the effects of intracerebral microinjection of sodium acamprosate are sitespecific (only effective in the bed nucleus of the stria terminalis) and dose dependent… These data provide evidence that sodium acamprosate is an active molecule affecting ethanol self-administration.' Others relate to a single experiment published as an abstract 12 years ago, in comparison to > 100 original investigations in rats that used systemic injections.…”

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confidence: 99%

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Reply to: Does acamprosate really produce its anti-relapse effects via calcium? No support from the PREDICT study in human alcoholics

Spanagel

Vengeliene

Kiefer

2016

Neuropsychopharmacol

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We have recently published surprising findings on the mode of action of acamprosate (Campral-calcium-bis (N-acetylhomotaurinate), which is clinically used for relapse prevention in alcohol-dependent patients. In this publication we concluded that N-acetylhomotaurinate is a biologically inactive molecule and that the effects of systemic applied acamprosate may be attributed to calcium (Spanagel et al, 2014). For this conclusion, we invested several years of work and provided convergent evidence from three different animal models and two different laboratories, with all animal experiments done in a blinded manner. In the same publication we also included an explorative human study where we provided additional evidence that calcium is the active component of acamprosate. Mann et al (2015) now challenge the human data provided by us and show in their PREDICT sample that plasma calcium levels are not correlated with treatment outcome. Here we argue that the PREDICT sample cannot be used to prove or disprove our conclusions. First, the PREDICT study failed to show any treatment effect of acamprosate in comparison to placebo treatment (Mann et al, 2013). The logic is as follows: if calcium is the active moiety of acamprosate, and acamprosate does not produce a positive treatment effect in a randomized controlled trial, how then should calcium be associated with treatment outcome? Second, the now presented re-evaluation of the PREDICT data based on 76 acamprosate-and 25 placebo-treated patients with available plasma calcium levels was underpowered to detect any treatment effect (Rösner et al, 2010).Mann and colleagues bring up also two other points of criticism: they state 'While Spanagel et al (2014) used systemic application others have shown that the effects of intracerebral microinjection of sodium acamprosate are sitespecific (only effective in the bed nucleus of the stria terminalis) and dose dependent… These data provide evidence that sodium acamprosate is an active molecule affecting ethanol self-administration.' Others relate to a single experiment published as an abstract 12 years ago, in comparison to > 100 original investigations in rats that used systemic injections. However, the critical point here is that we never claimed that N-acetylhomotaurinate given intracerebrally is devoid of effect. But as long as we do not inject acamprosate into the bed nucleus of the stria terminalis of alcohol-dependent patients, all of our statements about the inefficiency of systemic N-acetylhomotaurinate application are still correct.Mann et al also raised doubts as to whether our animal models can produce meaningful results. However, they should take into account that the efficacy of acamprosate on excessive alcohol consumption was discovered first in animal models and then translated to the human situation (Boismare et al, 1984).In conclusion, we provide convincing evidence that Nacetylhomotaurinate is a biologically inactive molecule and that the effects of systemically given acamprosate can be attributed to calcium. The...

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Acamprosate for alcohol dependence

Cited by 77 publications

References 1 publication

Consumo de alcohol, dependencia alcohólica, trastornos relacionados con el alcohol en España. Impacto de los tratamientos de la dependencia alcohólica

Consumo de alcohol, dependencia alcohólica, trastornos relacionados con el alcohol en España. Impacto de los tratamientos de la dependencia alcohólica

Acamprosate Produces Its Anti-Relapse Effects Via Calcium

Reply to: Does acamprosate really produce its anti-relapse effects via calcium? No support from the PREDICT study in human alcoholics

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