Efficacy of Naltrexone and Acamprosate for Alcoholism Treatment: A Meta‐Analysis

Kranzler, Henry R.; Kirk, Jeffrey Van

doi:10.1111/j.1530-0277.2001.tb02356.x

Cited by 358 publications

(75 citation statements)

References 48 publications

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“…Heavy drinking was defined as five or more drinks in a single day for men, four or more for women. [25][26][27] Additional outcome assessments included the Short Inventory of Problems (SIP); 28 the contemplation ladder; 29 and the Short Form-12 (SF12), which were also done at baseline. 30 The SIP is a measure of alcohol-related problems and the SF12 is a measure of quality of life with a physical (PCS) and mental (MCS) domain.…”

Section: Outcome Measuresmentioning

confidence: 99%

A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment

et al. 2013

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BACKGROUND: Alcohol use disorder is one of the leading causes of disability worldwide. Despite the availability of efficacious treatments, few individuals with an alcohol use disorder are actively engaged in treatment. Available evidence suggests that primary care may play a crucial role in the identification of patients with an alcohol use disorder, delivery of interventions, and the success of treatment. OBJECTIVE: The principal aims of this study were to test the effectiveness of a primary care-based Alcohol Care Management (ACM) program for alcohol use disorder and treatment engagement in veterans. DESIGN: The design of the study was a 26-week singleblind randomized clinical trial. The study was conducted in the primary care practices at three VA medical centers. Participants were randomly assigned to treatment in ACM or standard treatment in a specialty outpatient addiction treatment program. PARTICIPANTS: One hundred and sixty-three alcoholdependent veterans were randomized. INTERVENTION: ACM focused on the use of pharmacotherapy and psychosocial support. ACM was delivered in-person or by telephone within the primary care clinic. MAIN MEASUREMENTS: Engagement in treatment and heavy alcohol consumption. KEY RESULTS: The ACM condition had a significantly higher proportion of participants engaged in treatment over the 26 weeks [OR=5.36, 95 % CI = (2.99, 9.59)]. The percentage of heavy drinking days were significantly lower in the ACM condition [OR=2.16, 95 % CI= (1.27, 3.66)], while overall abstinence did not differ between groups. CONCLUSIONS: Results demonstrate that treatment for an alcohol use disorder can be delivered effectively within primary care, leading to greater rates of engagement in treatment and greater reductions in heavy drinking.

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Section: Outcome Measuresmentioning

confidence: 99%

A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment

et al. 2013

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“…Although this definition of heavy drinking has been used in a number of pharmacotherapy trials (O'Malley et al, 1992;Volpicelli et al, 1992;Anton, 1996;Kranzler and VanKirk, 2001), both higher and lower levels of consumption could be considered significant. This outcome was also among the primary hypothesized outcomes for each of the trials.…”

Section: Assessment Instrumentsmentioning

confidence: 99%

“…Although the efficacy of naltrexone has been established in a number of randomized clinical trials, no trial has demonstrated efficacy for all subjects and, overall, the published clinical trials demonstrate only modest response effect sizes (Kranzler and VanKirk, 2001;Streeton and Whelan, 2001). This lack of marked effects has been one of the reasons cited by providers to explain the relatively low utilization of naltrexone in clinical settings (Thomas et al, 2001).…”

Section: Table 1 Baseline Demographics and Clinical Characteristics Omentioning

confidence: 99%

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

552

399

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This study examined the association between two specific polymorphisms of the gene encoding the m-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A +118 G (Asn40Asp) and C +17 T (Ala6Val) SNPs in the gene encoding the m-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p ¼ 0.044) and a longer time to return to heavy drinking (p ¼ 0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p ¼ 0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a m-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

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“…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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Efficacy of Naltrexone and Acamprosate for Alcoholism Treatment: A Meta‐Analysis

Cited by 358 publications

References 48 publications

A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment

A Randomized Clinical Trial of Alcohol Care Management Delivered in Department of Veterans Affairs Primary Care Clinics Versus Specialty Addiction Treatment

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

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

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