United Kingdom Multicentre Acamprosate Study (Ukmas): A 6-Month Prospective Study of Acamprosate Versus Placebo in Preventing Relapse After Withdrawal From Alcohol

Chick, Jonathan; Howlett, H. C. S.; Morgan, Marsha Y.; Ritson, Bruce

doi:10.1093/alcalc/35.2.176

Cited by 196 publications

(133 citation statements)

References 36 publications

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“…Thus, screening for alcohol-related problems among trauma patients, as well as intervention (from brief counselling to referral for alcoholdependence treatment) is of relevance, although in practice this is poorly enforced (NHTSA, 2000;Runge, 2000). It is well known that there is a marked drop-out rate among alcohol-dependent patients during treatment (Noone and Watt, 2000;Chick et al, 2000). This is reflected in our study, the initial number of patients included was 176 and after the 12 months of treatment, more than half (107) had dropped out, with only 69 patients remaining in the study.…”

Section: Discussionmentioning

confidence: 99%

Road traffic accidents among alcohol-dependent patients: The effect of treatment

Gomez-Talegon

Álvarez

2006

Accident Analysis & Prevention

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It is well known that driving under the influence of alcohol increases the risk of traffic accidents. Alcohol-dependent patients are responsible for two-thirds of motor vehicle crashes involving alcohol. Studies carried out on the general population have shown a relation between alcohol dependence and traffic accidents.The aim of the study is to analyse the effect on traffic accidents of treatment of patients with alcohol-related problems. To do so, the prevalence of traffic problems in a sample of patients with a diagnosed dependence on alcohol was assessed for three periods: during their lifetime, in the year preceding the start of treatment and over the year of treatment.A prospective study was carried out of 176 patients (147 males, 29 females; mean age 42.9 years) diagnosed as alcohol dependent according to the DSM-IV criteria in three alcoholic treatment centres in Castilla y León, Spain.36.9% of the alcohol-dependent patients had had some kind of traffic problem during their life and 8.5% in the year prior to starting treatment. The most frequent problem was positive breath tests, followed by accidents with damage to the vehicle. Sixty-nine of the 176 patients were still receiving treatment after a year. The prevalence of traffic problems among those patients who followed treatment for 1 year (4.3%) was lower than in the year before treatment (15.9%).The study showed that the treatment is also effective in reducing traffic problems.

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Section: Discussionmentioning

confidence: 99%

Road traffic accidents among alcohol-dependent patients: The effect of treatment

Gomez-Talegon

Álvarez

2006

Accident Analysis & Prevention

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“…However, naltrexone's maintenance of abstinence in alcoholdependent patients was not remarkable in one study (Guardia et al 2002) and was absent in another (Krystal et al 2001). Chick et al (2000) provided disappointing effectiveness of acamprosate in their investigation. It is important to note that continuous use of opiate antagonists induces a rebound increase in central opiate receptors (Cowen et al 1999;Overstreet et al 1999;Parkes and Sinclair 2000).…”

Section: Future Directionsmentioning

confidence: 97%

“…Opiate antagonists (Heinälä et al 2001;Litten and Allen 1998;O'Malley et al 1992;Monti et al 2001;Rubio et al 2001;Volpicelli et al 1992), acamprosate (Ansoms et al 2000;Besson et al 1998;Chick et al 2000;Lesch et al 2001;Rubio et al 2001;Sass et al 1996;Tempesta et al 2000;Litten and Allen 1998; see overview by Mason 2001) or a combination of these drugs (Kranzler and Van Kirk 2001) are currently prescribed to reduce alcohol consumption in alcoholics. In preclinical studies, opiate antagonists are capable of minimizing acute drinking of alcohol (Altshuler et al 1980;Badia-Elder et al 1999;Froehlich et al 1990;Heyser et al 2003;Hölter and Spanagel 1999;Hyytia and Sinclair 1993;Overstreet et al 1999;Samson and Doyle 1985), as well as reducing alcohol seeking by an alcohol conditioned stimulus (Liu and Weiss 2002a;Koob et al 2003).…”

Section: Future Directionsmentioning

confidence: 99%

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

2004

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Rationale-The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse.Objective and results-An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence-a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis.Conclusions-The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse-and with relapse an inability to limit an abusive pattern of alcohol intake. The "kindling"/stress hypothesis provides a clear strategy for future studies to explore the advancing neural adaptation proposed to contribute to the pathogenesis of alcoholism.

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“…Pharmacovigilance data [23] in 1.5 million patients indicated no serious adverse events, and a Cochrane review [6] found the most common side effects (significantly different to placebo) to be gastro-intestinal symptoms (see Table 1) especially diarrhoea (effect size 0.11[0.09-0.13]) . If diarrhoea is severe, temporary dose reduction was beneficial [22,24]. More recent studies not included in earlier meta-analyses [25,26] confirm these earlier findings, diarrhoea being reported significantly more frequently in the acamprosate group, 1998mg/d (p=.004), and nervousness/ anxiety in the placebo group (p=.002) [26].…”

Section: Pharmacokinetic Considerations and Implications For Safetymentioning

confidence: 67%

“…there are reports from two studies of three patients taking intentional overdoses of 8-120 tablets with no 'untoward symptoms' [19,22].…”

Section: Pharmacokinetic Considerations and Implications For Safetymentioning

confidence: 99%

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

et al. 2016

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Alcohol use disorders (AUD) cause significant morbidity and mortality worldwide, but pharmacological treatments for them are underused, despite evidence of efficacy.Acamprosate, naltrexone, nalmefene and disulfiram are all approved in one or more region for the treatment of alcohol use disorders. Baclofen currently has a temporary indication in France. Safety considerations for using psychopharmacological treatments in this patient group include the impact of concurrent alcohol consumption at high levels, multiple physical comorbidities which may interfere with pharmacological effects, distribution and metabolism, and concomitant medication for the treatment of comorbid physical and psychiatric conditions. The five drugs, including an extended-release injectable suspension of naltrexone, have different safety profiles which need to be balanced with the objective of treatment (initiation or continuation of abstinence, or reduction of drinking), individual patient preferences and comorbid conditions. Appropriate treatment will be based on the unique riskbenefit profile in each case. KEY POINTS Acamprosate has an excellent safety profile and is recommended as first line treatment for patients wishing abstinence. Naltrexone and nalmefene are contraindicated with opioid-containing medication, but have reasonable tolerability  The disulfiram-alcohol reaction is integral to its use, but careful patient selection and monitoring can mitigate safety risks  Baclofen is a CNS depressant so there are potential concerns regarding overdose: it may have a role in patients with severe liver disease Pharmacological treatments for alcohol dependence 3

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United Kingdom Multicentre Acamprosate Study (Ukmas): A 6-Month Prospective Study of Acamprosate Versus Placebo in Preventing Relapse After Withdrawal From Alcohol

Cited by 196 publications

References 36 publications

Road traffic accidents among alcohol-dependent patients: The effect of treatment

Road traffic accidents among alcohol-dependent patients: The effect of treatment

Conceptual framework for the etiology of alcoholism: a ?kindling?/stress hypothesis

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

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