Amato L, Minozzi S, Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the alcohol withdrawal syndrome. Cochrane Database Syst Rev CD008537

Department of Epidemiology, ASL RM/E, Via di Santa Costanza, 53, Rome, Italy, 00198.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 06/2011; 6(6):CD008537. DOI: 10.1002/14651858.CD008537.pub2
Source: PubMed


Alcohol abuse and dependence represents a very serious health problem worldwide with major social, interpersonal and legal interpolations. Pharmacological treatments presently used are of uncertain effectiveness and there is even more doubt on the comparative effects and value for money.
To summarize Cochrane reviews that assess the effectiveness and safety of pharmacological interventions in the treatment of alcohol withdrawal.
We searched the Cochrane Database of Systematic Reviews (30 November 2010). Two authors independently screened, extracted data, summarised key characteristics of the included reviews and assessed their quality using AMSTAR; the quality of the evidence was summarised according to the GRADE methodology.
Five reviews, 114 studies, 7333 participants, satisfied criteria for inclusions. The outcomes considered were alcohol withdrawal seizures, adverse events and dropouts. Comparing the five treatments with placebo, benzodiazepines performed better for seizures, three studies, 324 participants, RR 0.16 (95% CI 0.04 to 0.69), moderate quality of evidence. Comparing each of the five treatments versus specific class of drugs, benzodiazepines performed better than antipsychotics for seizures, 4 studies, 633 participants, RR 0.24 (95% CI 0.07 to 0.88) high quality of the evidence. Comparing different benzodiazepines and anticonvulsants among themselves, 28 comparisons, results never reached statistical significance but chlordiazepoxide performed better. The quality of evidence was high for 3% of the results, moderate for 28%, low for 48% and very low for 20%.
Among the treatments considered, benzodiazepines showed a protective benefit against seizures, when compared to placebo and a potentially protective benefit for many outcomes when compared with antipsychotics. Nevertheless, no definite conclusions about the effectiveness and safety of benzodiazepines were possible, because of the heterogeneity of the trials both in interventions and in the assessment of outcomes. Data on potential harms are sparse and fragmented. Results do not provide sufficient evidence in favour of anticonvulsants for the treatment of AWS, but anticonvulsants seem to have limited side effects. There is also not enough evidence of effectiveness and safety of baclofen, because only one study consider this treatment and of GHB for which no strong differences were observed in the comparisons with placebo, benzodiazepines and anticonvulsants.

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    • "This scoring system allows a quantitative evaluation of AWS severity and enhances identification of subjects potentially requiring pharmacological treatment. In addition to administration of fluids, thiamine, and electrolytes, benzodiazepines represent the current drugs of choice in the treatment of AWS (Amato et al., 2010, 2011). However, benzodiazepines may feature addictive properties, representing a major limitation to their use in subjects affected by AUD (Leggio et al., 2008). "
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    ABSTRACT: The present paper summarizes the preclinical and clinical studies conducted to define the "anti-alcohol" pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date-including case reports, retrospective chart reviews, and randomized placebo-controlled studies-suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several "anti-alcohol" effects of baclofen and display a higher therapeutic index (with larger separation-in terms of doses-between "anti-alcohol" effects and sedation).
    Frontiers in Neuroscience 06/2014; 8(8):140. DOI:10.3389/fnins.2014.00140 · 3.66 Impact Factor
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    • "Currently, benzodiazepines are the drugs of choice for the treatment of AWS (reviewed by Amato et al, 2011). These compounds potentiate GABA-A receptor signaling and act to counterbalance the hyperexcitation produced by excessive glutamate transmission. "
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    ABSTRACT: Alcohol Withdrawal Syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first-line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations. After a two-week period of habituation to ethanol in two-bottle choice, alcohol-preferring (P) and Wistar rats received ethanol (4.0 g/kg) every 6 hours for 3-5 consecutive days via gavage. Rats were then deprived of ethanol for 48 h during which time they received ceftriaxone (50 mg or 100 mg/kg, I.P.) or saline twice a day starting 12 h after the last ethanol administration. Withdrawal manifestations were captured by continuous video recording and coded. The evolution of ethanol withdrawal was markedly different for P rats versus Wistar rats, with withdrawal manifestations occurring >12 h later in P rats than in Wistar rats. Ceftriaxone 100 mg/kg/injection twice per day (200 mg/kg/day) reduced or abolished all manifestations of ethanol withdrawal in both rat variants and prevented withdrawal-induced escalation of alcohol intake. Finally, ceftriaxone treatment was associated with lasting upregulation of ethanol withdrawal-induced downregulation of EAAT2 in the striatum. Our data support the role of ceftriaxone in alleviating alcohol withdrawal and open a novel pharmacologic avenue that requires clinical evaluation in patients with AWS.Neuropsychopharmacology accepted article preview online, 23 January 2014. doi:10.1038/npp.2014.14.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 01/2014; 39(7). DOI:10.1038/npp.2014.14 · 7.05 Impact Factor
    • "They unequivocally reduce the risk of severe alcohol withdrawals like seizures or DT.[17] Among the benzodiazepines, chlordiazepoxide has a slight advantage over the other benzodiazepines or anticonvulsants.[18] Anticonvulsants have not been proven to be better than benzodiazepines. "
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    ABSTRACT: Alcohol withdrawal is commonly encountered in general hospital settings. It forms a major part of referrals received by a consultation-liaison psychiatrist. This article aims to review the evidence base for appropriate clinical management of the alcohol withdrawal syndrome. We searched Pubmed for articles published in English on pharmacological management of alcohol withdrawal in humans with no limit on the date of publication. Articles not relevant to clinical management were excluded based on the titles and abstract available. Full-text articles were obtained from this list and the cross-references. There were four meta-analyses, 9 systematic reviews, 26 review articles and other type of publications like textbooks. Alcohol withdrawal syndrome is a clinical diagnosis. It may vary in severity. Complicated alcohol withdrawal presents with hallucinations, seizures or delirium tremens. Benzodiazepines have the best evidence base in the treatment of alcohol withdrawal, followed by anticonvulsants. Clinical institutes withdrawal assessment-alcohol revised is useful with pitfalls in patients with medical comorbidities. Evidence favors an approach of symptom-monitored loading for severe withdrawals where an initial dose is guided by risk factors for complicated withdrawals and further dosing may be guided by withdrawal severity. Supportive care and use of vitamins is also discussed.
    Industrial psychiatry journal 07/2013; 22(2):100-8. DOI:10.4103/0972-6748.132914
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