The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta‐analysis

Donoghue, Kim; Elzerbi, Catherine; Saunders, Rob; Whittington, Craig; Pilling, Stephen; Drummond, Colin

doi:10.1111/add.12875

Cited by 101 publications

(79 citation statements)

References 58 publications

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“…Acamprosate has low oral bioavailability (approximately 11%), is not protein bound, and is not metabolised by the liver, being excreted unchanged in urine [13]. The evidence base includes three recent systematic reviews and metaanalyses [4,6,15] …”

Section: Acamprosatementioning

confidence: 99%

“…It is subject to significant first pass metabolism, creating the primary active metabolite 6-beta-naltrexol, which has a half-life of 13 hours [39], the levels of which correlate with adverse events [40]. A substantial evidence base includes systematic reviews and meta-analyses, which demonstrate a significant effect for naltrexone over placebo on relapse rates in heavy drinking (RR 0.83; 95% CI:0.75 to 0.91) [4], and on relapse to any drinking at 3 months (RR = 0.92, 95% CI = 0.86-1.00) [15].…”

Section: Oral Naltrexonementioning

confidence: 99%

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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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Section: Acamprosatementioning

confidence: 99%

Section: Oral Naltrexonementioning

confidence: 99%

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

et al. 2016

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“…It has been shown that naltrexone significantly reduces the number of drinking days and the level of alcohol craving [8], with a number needed to treat to prevent a relapse into heavy drinking of 9 [9]. Comparably, the anticraving drug, acamprosate, has been shown to reduce the risk of relapse into any drinking [10], with a number needed to treat to prevent a relapse of 8 [9]. In clinical practice, naltrexone or acamprosate are both considered firstchoice pharmacological treatments, and are prescribed with similar frequencies [5,6,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…Comparably, the anticraving drug, acamprosate, has been shown to reduce the risk of relapse into any drinking [10], with a number needed to treat to prevent a relapse of 8 [9]. In clinical practice, naltrexone or acamprosate are both considered firstchoice pharmacological treatments, and are prescribed with similar frequencies [5,6,10,11].…”

Section: Introductionmentioning

confidence: 99%

“…This might be due to the side effects of naltrexone and acamprosate, such as nausea, headache, dizziness, anxiety, and diarrhea [5,8,10,13], and medication contraindications: kidney failure for both naltrexone and acamprosate; liver issues for naltrexone [13]. Hence, healthcare professionals are sometimes skeptical about the role of pharmacotherapy in the treatment of addictive behaviors [14].…”

Section: Introductionmentioning

confidence: 99%

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Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach

Sluiter¹,

Kievit²,

Wilt³

et al. 2018

Eur Addict Res

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Alcohol use disorders (AUD) are a major contributor to the global burden of disease, and have huge societal impact. Some studies show that AUD patients carrying the G-allele of the OPRM1 variant c.118A>G respond better to naltrexone, resulting in reduced relapse rates compared to carriers of the AA genotype. Genotype-guided treatment allocation of these patients carrying a G-allele to naltrexone could potentially improve the treatment outcome. However, cost-effectiveness of this strategy should be investigated before considering clinical implementation. We, therefore, evaluated costs and Quality-Adjusted Life-Years (QALYs), using a modelling approach, from an European perspective, of genotype-guided treatment allocation (G-allele carriers receiving naltrexone; AA homozygotes acamprosate or naltrexone) compared to standard care (random treatment allocation to acamprosate or naltrexone), by using a Markov model. Genotype-guided treatment allocation resulted in incremental costs of EUR 66 (95% CI –28 to 149) and incremental effects of 0.005 QALYs (95% CI 0.000–0.011) per patient (incremental cost-effectiveness ratio of EUR 13,350 per QALY). Sensitivity analyses showed that the risk ratio to relapse after treatment allocation had the largest impact on the cost-effectiveness. Depending on the willingness to pay for a gain of one QALY, probabilities that the intervention is cost-effective varies between 6 and 79%. In conclusion, pharmacogenetic treatment allocation of AUD patients to naltrexone, based on OPRM1 genotype, can be a cost-effective strategy, and could have potential individual and societal benefits. However, more evidence on the impact of genotype-guided treatment allocation on relapse is needed to substantiate these conclusions, as there is contradictory evidence about the effectiveness of OPRM1 genotyping.

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Diagnosis and Pharmacotherapy of Alcohol Use Disorder

Kranzler

Soyka

2018

JAMA

476

356

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Alcohol consumption is associated with a high rate of morbidity and mortality, and heavy alcohol use is the major risk factor for AUD. Simple, valid screening methods can be used to identify patients with heavy alcohol use, who can then be evaluated for the presence of an AUD. Patients receiving a diagnosis of the disorder should be given brief counseling and prescribed a first-line medication (eg, naltrexone) or referred for a more intensive psychosocial intervention.

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The efficacy of acamprosate and naltrexone in the treatment of alcohol dependence, Europe versus the rest of the world: a meta‐analysis

Cited by 101 publications

References 58 publications

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

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

Cost-Effectiveness Analysis of Genotype-Guided Treatment Allocation in Patients with Alcohol Use Disorders Using Naltrexone or Acamprosate, Using a Modeling Approach

Diagnosis and Pharmacotherapy of Alcohol Use Disorder

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