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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    • "Benzodiazepine im Alkoholentzugssyndrom ist durch zahlreiche Studien und mehrere systematische Reviews im Vergleich zu Placebo, zu Clomethiazol, zu Anikonvulsiva und zu anderen Substanzen gut belegt[1,2,11,48,56]. Benzodiazepine werden weltweit am häufigsten zur Behandlung des Alkoholentzugssyndroms eingesetzt und in internationalen Leitlinien als primäre Therapieoption empfohlen[3,7,16,54]. Am häufigsten wurden Chlordiazepoxid, Diazepam, Lorazepam und Oxazepam untersucht[1,2], ohne dass sich gesicherte Unterschiede bezüglich der Wirksamkeit der Benzodiazepine untereinander ergeben hätten. Benzodiazepine reduzieren effektiv die Schwere und Häufigkeit von Symptomen des Alkoholentzugssyndroms (Tremor , Unruhe, Schlafstörungen, Hypertonus etc.) sowie die Häufigkeit schwererer Entzugskomplikationen wie Delire und Entzugskrampfanfälle[48,54,56].[30], die vermehrt während der intravenösen Haloperidol- Anwendung auftreten sollen, obwohl Haloperidol diesbezüglich nicht risikobehafteter als andere Antipsychotika sein soll[28].[3,5,11,13,16,39,43,46,48,49,52535467]). "
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    ABSTRACT: Alcohol use disorders (e.g. abuse and dependence) account for a plethora of consequences for affected individuals and for a substantial proportion of the overall burden of disease for the community. To date, existing treatment options are either poorly known by doctors or they are not fully applied and only approximately 15 % of potential patients are treated with a mean latent period of 10 years between early symptoms and the first intervention. So-called S3 treatment guidelines were recently developed to close this gap. Representatives of more than 50 learned societies, families and patients were involved. A systematic literature search from 2005 to 2012 was performed and more than 120 recommendations were made. Financing came exclusively from those societies and the academic and treatment institutes involved. This article summarizes the recommendations pertinent for psychiatrists and include early detection and intervention, acute withdrawal and long-term psychotherapy and pharmacotherapy. Classical and new treatment goals are discussed. If the new guidelines were properly applied an increase in patients receiving treatment to 30–40 % could be expected, which would improve the quality of lives of affected persons and their families and in Germany would save several thousand lives per year.
    Full-text · Article · Dec 2015 · Der Nervenarzt
    • "Perform blood tests (blood Assess CAGE and/or AUDIT alcohol concentraon, liver enzymes, gGT, MCV, glucose, electrolytes). Fig. 1Proposed flow-chart in the diagnosis and treatment of alcohol withdrawal syndrome[54]. In these cases, oxazepam and lorazepam represent the drugs of choice due to the absence of oxidative metabolism and active metabolites (Table 5)[21,53,60]. "
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    ABSTRACT: Symptoms of alcohol withdrawal syndrome (AWS) may develop within 6-24 h after the abrupt discontinuation or decrease of alcohol consumption. Symptoms can vary from autonomic hyperactivity and agitation to delirium tremens. The gold-standard treatment for AWS is with benzodiazepines (BZDs). Among the BZDs, different agents (i.e., long-acting or short-acting) and different regimens (front-loading, fixed-dose or symptom-triggered) may be chosen on the basis of patient characteristics. Severe withdrawal could require ICU admission and the use of barbiturates or propofol. Other drugs, such as α2-agonists (clonidine and dexmetedomidine) and β-blockers can be used as adjunctive treatments to control neuroautonomic hyperactivity. Furthermore, neuroleptic agents can help control hallucinations. Finally, other medications for the treatment for AWS have been investigated with promising results. These include carbamazepine, valproate, sodium oxybate, baclofen, gabapentin and topiramate. The usefulness of these agents are discussed.
    No preview · Article · Mar 2015 · Drugs
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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).
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