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

Department of Psychology, Washington State University Vancouver, Vancouver, WA, USA.
Therapeutics and Clinical Risk Management (Impact Factor: 1.34). 02/2012; 8:45-53. DOI: 10.2147/TCRM.S23184
Source: PubMed

ABSTRACT 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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    ABSTRACT: Alcohol withdrawal syndrome is associated with increased central N-methyl-D-aspartate (NMDA) glutamate transmission. Medications that reduce glutamate release or block NMDA overactivation have shown efficacy for treating alcohol withdrawal syndrome. Dextromethorphan (DXM), a widely used antitussive drug, is a low-affinity, noncompetitive NMDA antagonist with potential neuroprotective properties. This study, using a randomized, double-blind, placebo-controlled study design, examined the benefit of DXM in the management of acute alcohol withdrawal. Alcohol-dependent patients admitted for detoxification treatment and experiencing moderate alcohol withdrawal, as measured by a score greater than 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), were randomly assigned to receive either DXM 360 mg/d or an identical placebo for 7 days in a double-blind manner. All subjects received a concurrent dose of lorazepam 2 mg along with the initial administration of DXM or placebo and were given additional lorazepam (1 mg) as a rescue medication according to the symptom-triggered detoxification protocol. Outcome measures consisted of the mean total dose of lorazepam received, the sequential scores on the CIWA-Ar, and craving assessed by the Obsessive-Compulsive Drinking Scale. Forty subjects completed the study, 18 in the DXM group and 22 in the placebo group. We found that compared with placebo, DXM use was not associated with lower lorazepam doses to control alcohol withdrawal symptoms. The progression in CIWA-Ar and Obsessive-Compulsive Drinking Scale scores was also comparable between the 2 groups. Our preliminary results do not support the efficacy of high-dose DXM in reducing the need of benzodiazepines to treat withdrawal symptoms in alcohol-dependent patients.
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    ABSTRACT: The alcoholism can also deal with drug treatments." This is the message that emerges from the press conference of presentation of Campral, trade name of acamprosate, a neuromodulator specifically indicated in the maintenance of abstinence in alcohol-dependent patients.Alcoholism is a disease characterized by: craving, loss of control, tolerance and physical dependence.For many years the prevention of relapse in use of alcohol after detoxification was supported almost exclusively by psychosocial procedures and techniques with modest success. Treatment with acamprosate is a valid tool to complement psychotherapy as it does not cause addiction, abuse or withdrawal of its suspension and does not interfere with other medications that patients often alcoholics must take.To evaluate the effectiveness, our study evaluated the effects of Acamprosate compared to GHB in clinical-physiological and social health in a way indicators of a possible therapeutic success in terms of abstinence from alcohol and social reintegration. The hypothesis of the project is that pharmacotherapy anticraving with acamprosate integrated with psycho-social support, can reduce relapse in alcohol together with the reduction of the risk of abuse arising from the use of GHB. This work purports to be an account of 11 months of observation of patients treated with acamprosate. Results: A total of 36 patients were observed, of which 5, 4 men and 1 woman at the Ser.T Alcamo and 31, 21 men and 10 women at the Ser.T of Palermo. In the fight against alcoholism, this therapy with acamprosate offers significant potential: decreases, in fact, the incidence, severity and frequency of relapses (Fig. 1). As regards the craving, during the period of treatment with acamprosate, there has been a change, in the sense of reduction, of craving for alcohol: if before therapy was in 68% of cases, medium-high, becomes after 3-4 months after therapy in low-nil in 89% of patients observed. It has been recorded that, after 3-4 months after receiving acamprosate, the clinical picture of the patient is greatly improved by referring to biological markers (Fig. 2). Conclusions: The study shows that treatment with acamprosate is an exciting opportunity within a project of integrated care for the treatment of alcohol addiction. The acamprosate may also be used early in the pharmacological treatment of dependence on alcohol to prevent the appearance of excitability neuronal associated abstinence.On the other hand, its use must have a duration sufficient to allow neuronal excitability to normalize in the most enduring possible: the treatment, in fact, is recommended for one year. In any case, the use can be continued even in the face of relapses, with the aim to reduce the frequency or severity.In particular, the strong point seems to be the ability for the user to experience a new sense of normalcy and to remove the desire for significant periods of alcohol.
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    ABSTRACT: The present study investigated the effect of acamprosate on ethanol (EtOH)-induced place preference in mice with EtOH physical dependence. The expression of EtOH (2 g/kg, intraperitoneally)-induced place preference in mice without EtOH treatment before the experiment was dose-dependently suppressed by acamprosate. The levels of protein kinase A (PKA) and phospho-cAMP response element binding protein (p-CREB) in the limbic forebrain after EtOH-conditioning in naïve mice was unchanged. Furthermore, mice on the 4th day of withdrawal from continuous EtOH vapor inhalation for 9 days showed transient and significant enhancement of EtOH (1 g/kg, intraperitoneally)-induced place preference, which was significantly suppressed by acamprosate (300 mg/kg, oral administration; p.o., once a day) administered daily for 3 days after withdrawal from EtOH inhalation and during EtOH-conditioning. PKA and p-CREB proteins in the limbic forebrain of EtOH-conditioned mice on 4th day of withdrawal from continuous EtOH inhalation for 9 days significantly increased, which were completely abolished by acamprosate. These findings suggest that the signal transduction pathway via the PKA-p-CREB pathway in the limbic forebrain may be functionally related to the development of sensitization of EtOH-induced place preference and provide a possible molecular basis for the pharmacological effect of acamprosate to prevent or reduce the relapse of alcohol dependence.
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