Why is Disulfiram Superior to Acamprosate in the Routine Clinical Setting? A Retrospective Long-Term Study in 353 Alcohol-Dependent Patients

Diehl, Alexander; Ulmer, Lisa; Mutschler, Jochen; Herre, H.; Krumm, Bertram; Croissant, Bernhard; Mann, Karl; Kiefer, Falk

doi:10.1093/alcalc/agq017

Cited by 46 publications

(28 citation statements)

References 33 publications

(28 reference statements)

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“…8 This result is in line with previously published data. 4 One could argue that our subjects may represent a less severe phenotype of alcohol addiction.…”

Section: Discussionsupporting

confidence: 93%

Safety and Efficacy of Long-Term Disulfiram Aftercare

Mutschler

Dirican

Gutzeit

et al. 2011

Clinical Neuropharmacology

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“…8 This result is in line with previously published data. 4 One could argue that our subjects may represent a less severe phenotype of alcohol addiction.…”

Section: Discussionsupporting

confidence: 93%

Safety and Efficacy of Long-Term Disulfiram Aftercare

Mutschler

Dirican

Gutzeit

et al. 2011

Clinical Neuropharmacology

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“…The superiority of disulfiram over acamprosate and naltrexone has been demonstrated (see, e.g. de Sousa and de Sousa, 2004, 2005; Laaksonen et al , 2008; Diehl et al ., 2010). However, safety issues with disulfiram (Chick, 1999) suggest the need for developing safer alternative ALDH inhibitors for alcoholism treatment.…”

Section: Introductionmentioning

confidence: 99%

Tryptophan in Alcoholism Treatment I: Kynurenine Metabolites Inhibit the Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Activity, Elevate Blood Acetaldehyde Concentration and Induce Aversion to Alcohol

Badawy

Bano

Steptoe

2011

Alcohol and Alcoholism

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Aims: The aims were to provide proofs of mechanism and principle by establishing the ability of kynurenine metabolites to inhibit the liver mitochondrial low Km aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to induce aversion to alcohol. Methods: Kynurenic acid (KA), 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar rats and ALDH activity was determined both in vitro in liver homogenates and in vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol consumption was studied in an aversion model in rats and in alcohol-preferring C57 mice. Results: ALDH activity was significantly inhibited by all three metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation after ethanol administration was strongly elevated by KA and 3-HK and to a lesser extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and decreased alcohol preference in mice. Conclusions: The above kynurenine metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity. An intellectual property covering the use of 3-HK and 3-HAA and derivatives thereof in the treatment of alcoholism by aversion awaits further development.

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“…However, the effects of acamprosate are only moderate in comparison with placebo and acamprosate has not been found to be consistently superior to naltrexone or disulfiram. Furthermore, there have not been any prospective studies evaluating the long-term (longer than one year) effectiveness of acamprosate in preventing lapse following discontinuation of the medication and retrospective studies have found the long-term effectiveness of acamprosate to be worse than that of disulfiram in a naturalistic clinical setting 61. Finally, it is imperative that more research be devoted to studying the mechanisms of efficacy for acamprosate and to determine whether certain patients are more or less likely to respond to this agent, as compared with other FDA-approved medications for alcohol dependence.…”

Section: Acamprosate In Clinical Practicementioning

confidence: 99%

Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility

Witkiewitz¹,

Saville²,

Hamreus³

2012

TCRM

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Acamprosate, or N-acetyl homotaurine, is an N-methyl-D-aspartate receptor modulator approved by the Food and Drug Administration (FDA) as a pharmacological treatment for alcohol dependence. The exact mechanism of action of acamprosate is still under investigation, but the drug appears to work by promoting a balance between the excitatory and inhibitory neurotransmitters, glutamate and gamma-aminobutyric acid, respectively, and it may help individuals with alcohol dependence by reducing withdrawal-associated distress. Acamprosate has low bioavailability, but also has an excellent tolerability and safety profile. In comparison with naltrexone and disulfiram, which are the other FDA-approved treatments for alcohol dependence, acamprosate is unique in that it is not metabolized by the liver and is also not impacted by alcohol use, so can be administered to patients with hepatitis or liver disease (a common comorbid condition among individuals with alcohol dependence) and to patients who continue drinking alcohol. Acamprosate has demonstrated its efficacy in more than 25 placebo-controlled, double-blind trials for individuals with alcohol dependence, and has generally been found to be more efficacious than placebo in significantly reducing the risk of returning to any drinking and increasing the cumulative duration of abstinence. However, acamprosate appears to be no more efficacious than placebo in reducing heavy drinking days. Numerous trials have found that acamprosate is not significantly more efficacious than naltrexone or disulfiram, and the efficacy of acamprosate does not appear to be improved by combining acamprosate with other active medications (eg, naltrexone) or with psychosocial treatment (eg, cognitive-behavioral therapy). In this review, we present the data on acamprosate, including its pharmacology, efficacy, safety, and tolerability in the treatment of alcohol dependence.

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Why is Disulfiram Superior to Acamprosate in the Routine Clinical Setting? A Retrospective Long-Term Study in 353 Alcohol-Dependent Patients

Abstract: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.

Cited by 46 publications

References 33 publications

Safety and Efficacy of Long-Term Disulfiram Aftercare

Safety and Efficacy of Long-Term Disulfiram Aftercare

Tryptophan in Alcoholism Treatment I: Kynurenine Metabolites Inhibit the Rat Liver Mitochondrial Low Km Aldehyde Dehydrogenase Activity, Elevate Blood Acetaldehyde Concentration and Induce Aversion to Alcohol

Acamprosate for treatment of alcohol dependence: mechanisms, efficacy, and clinical utility

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