Article

Opioid antagonists for alcohol dependence.

Department of Psychiatry, Chiang Mai University, P.O. Box 102, Amphur Muang, Chiang Mai 50202, Thailand.
Cochrane database of systematic reviews (Online) (Impact Factor: 5.94). 02/2005;
Source: PubMed

ABSTRACT Opioid antagonists can decrease alcohol consumption in animals. Their harms and benefits have been examined in many clinical trials.
To determine the effectiveness of opioid antagonists in attenuating or preventing the recommencement of alcohol consumption in patients with alcohol dependence in comparison to placebo, other medications and psychosocial treatments. In addition, discontinuation rate, death, patient satisfaction, functioning, health-related quality of life and economic outcomes were also evaluated.
The specialised register of the Cochrane Group on Drugs and Alcohol was searched until September 2003. The search was integrated with previous searches of Cochrane Controlled Trials Register (Cochrane Library 2001, issue 4), MEDLINE (1966 - October 2001), EMBASE (1980 - December 2001) and CINHAL (1982 - December 2001). Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials. The reference lists of the obtained papers were also examined.
All relevant randomised controlled trials (RCTs) were included. Participants were people with alcohol dependence. Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/without other biological or psychosocial treatments were examined. Two primary outcomes were number of participants with relapses (including those who return to heavy drinking) and number of participants who return to drinking. Other outcomes of interest were time to first drink, percentage or number of drinking days, number of standard drinks, craving, percentage or number of days or episodes of heavy drinking, amount of alcohol consumed, discontinuation rate, patient satisfaction, impaired function, health-related quality of life, economic and death.
Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis. The Relative Risk with the 95% confidence interval was used to assess the dichotomous data. A weighted (or standardised) mean difference (WMD or SMD) with 95% confidence interval was used to assess the continuous data.
The review included 29 RCTs presented in 36 articles. Except two RCTs of nalmefene, all others investigated NTX. In comparison to placebo, a short-term treatment of NTX significantly decreased the relapse [RR (95% CI) = 0.64 (0.51 to 0.82)] and was likely to decrease the return to drinking [RR (95% CI) = 0.87 (0.76 to 1.00). In the respect of acceptability, NTX treatment significantly diminished treatment withdrawal [RR (95% CI) = 0.82 (0.70 to 0.97). While a medium-term treatment of NTX gave no benefit in the respect of relapse prevention, it was found to be beneficial on two of four secondary outcomes by increasing time to first drink and diminishing craving. A medium-term treatment of NTX was superior to acamprosate in reducing relapses, standard drinks and craving. NTX plus an intensive psychosocial treatment (PST) was not superior to NTX plus a simple PST on any primary and secondary short-term outcomes. For a medium-term treatment, NTX plus an intensive PST was superior to NTX plus a simple PST in increasing time to first drink and decreasing craving.
The review findings support that short-term treatment of NTX decreases the chance of alcohol relapses for 36% (number-needed-to-treat or NNT = 7) and likely to reduce the chance of returning to drinking for 13% (NNT = 12). In comparison to placebo group, NTX treatment can lower the risk of treatment withdrawal in alcohol-dependent patients for 28% (NNT = 13). Some major limitations of the available evidence include short study duration in many trials, small sample sizes in most trials and lack of data on psychosocial benefits. In conclusion, NTX should be accepted as a short-term treatment for alcoholism. Strategies to improve adherence to NTX treatment, eg, PSTs and management of adverse effects, should be concomitantly given. We have not yet known so far how long alcohol-dependent patients who respond to NTX treatment should continue their treatment. Due to too little evidence, NMF should have no role for the treatment of alcohol dependence.

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    ABSTRACT: INHATA Structured Abstract Background: Alcohol dependence is a multifactorial condition involving elements of a diverse nature, namely, genetic, psychological, social and environmental factors that progressively incline the patient towards alcohol consumption until he/she becomes entrenched in a pattern of abuse, with its corresponding burden of medical and psychiatric co-morbidities. At the same time, therapeutic approaches may respond to goals as divergent as preventing the appearance or progress of related morbidities, preventing marginalisation, or fostering patients’ integration into the family, workplace and society. New neurobiological insights into this dependency, which link the associated craving to specific neuronal dysfunctions, have opened up a new pharmacotherapeutic line focused on reversing such disorders. This new approach relies on the so-called anticraving drugs, the best examples of which are: on the one hand, Naltrexone or, additionally, its methylene analogue, Nalmefene; and on the other, Acamprosate. Purpose of assessment: To evaluate the efficacy and safety of opioid antagonists and acamprosate in the treatment of alcohol dependence. Methods: Systematic review of medical literature, from January 1990 to September 2002. Search strategy: Electronic search covering: Medline, CINAHL and Embase (Pollution and Toxicology), using SilverPlatter WebSPIRS 4.30; and the Cochrane Controlled Trials Register. In addition, bibliographic references cited in the papers so obtained were also examined. Selection criteria: Randomised clinical trials and prospective clinical case-control studies that assess the efficacy and safety of one or more opioid antagonists or acamprosate in the treatment of alcohol dependence. Data collection and analysis: Data were abstracted and evaluated independently by two reviewers. The data were extracted on an intention-to-treat basis. The dichotomous outcomes were analysed using Peto’s odds ratio (OR) with 95% confidence interval; and continuous outcomes, using weighted mean difference with 95% confidence intervals. Cost/economic analysis: No. Expert opinion: No. Results: A total of 36 eligible studies were identified for inclusion in this review. Twenty studies compared naltrexone with placebo or a reference group without medication; two compared nalmefene with placebo, thirteen evaluated acamprosate and one study compared naltrexone and acamprosate. Thirty-four studies were randomised controlled simple or double-blinded trials and two were prospective controlled trials without randomisation. The principal findings were as follows: Naltrexone: 1. Studies evaluating Naltrexone-based treatment of alcohol dependence were, in general, of good quality though at times the sample size was small. 2. Ambulatory treatment with Naltrexone seems to be effective, reducing alcohol consumption in patients with alcohol dependence, though not significantly modifying the abstinence rate. 3. The benefits of treatment proved statistically significant in the following measures of efficacy: relapse rate, during both the active treatment and follow-up phases; time to relapse; percentage of drinking days; days of heavy drinking; number of standard drinks per drinking day; total consumption; and biological parameters. 4. There are data to suggest that Naltrexone may reduce the degree of craving. Nevertheless, assessment of this variable poses important methodological limitations. 5. Naltrexone’s effects persist while active treatment is under way, thereafter gradually declining over the follow-up period and ultimately disappearing altogether. 6. The literature consulted did not yield sufficient data for ascertainment of Naltrexone’s efficacy and safety in patients with multidependence. 7. Naltrexone seems to be acceptably tolerated without adverse effects significantly reducing the retention rate in the studies analysed. Nalmefene: Assessment of the efficacy and safety of Nalmefene was clearly limited by the scant sample size of the studies undertaken. Acamprosate: 1. Overall, Acamprosate trials possessed an adequate sample size and displayed good methodological quality. 2. Such studies, conducted in an ambulatory setting, show an effect significantly favourable to Acamprosate versus placebo in alcohol-dependent subjects who previously underwent a process of detoxification. 3. There is a good degree of evidence as to the drug’s efficacy in raising the continuous abstinence rate and cumulative period of abstinence. 4. Treatment benefits were significantly superior in longer-term studies and this superiority held across the follow-up period. 5. Although there are data to suggest that Acamprosate may reduce craving, assessment of this variable entails important limitations. 6. There are data to suggest a favourable effect on gamma-glutamyl transferase (GGT). 7. It is a well-tolerated drug with few side effects. However, treatment compliance rates were only moderate. Recommendations/Conclusions: This review has shown convincing evidence from good quality randomised controlled trials and prospective controlled clinical trials that naltrexone and acamprosate are moderately effective therapies for alcohol dependence. However, questions remain about the optimal duration of treatment; the type of patients who will benefit most from a specific drug; the impact of treatments on patients’ health-related quality of life and degree of satisfaction. Similarly, no evaluation was made of their effects on alcohol-dependence-related morbidity. In addition, further studies are needed to evaluate the appropriate selection of patients and to understand the relationship of pharmacotherapy to patient heterogeneity. Psychosocial interventions require more standardization and better reporting and the relationship of pharmacotherapy to these interventions needs to be better understood. Common outcome measures need to be standardized both in their definition and the way they are assessed. Studies should be made over longer time periods to establish the efficacy of both groups of drugs as maintenance treatments. Effectiveness studies are needed to establish the benefit of naltrexone and acamprosate in common clinical settings. In addition, future studies should examine ways to enhance both medication compliance and study retention.
    01/2002; AGENCIA DE EVALUACIÓN DE TECNOLOGÍAS SANITARIAS Instituto de Salud Carlos III - Ministerio de Sanidad y Consumo., ISBN: 84-95463-16-4
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