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Systematic review with meta-analysis.
CINAHL, EMBASE, MEDLINE, and the Cochrane Controlled Trials Register (January 1990 to September 2002) plus hand searches of reference lists.
Study selection and analysis:
Eligible studies were randomised controlled trials comparing naltrexone or acamprosate with placebo or a control group not taking any medication. Exclusions: <10 people in the study; less than 2 weeks’ follow up; lack of relevant primary clinical data; or no quantitative results. Data were extracted on study scope and design, randomisation process, sample size, intervention, exclusion and inclusion criteria, baseline characteristics, length of treatment and follow up, outcome, and treatment compliance. A random effects model was used to carry out meta-analysis. Peto’s odds ratios were used to measure dichotomous outcomes and weighted mean differences were used to measure continuous outcomes.
Relapse and abstinence rates; treatment compliance and duration of abstinence.
Thirty three studies met inclusion criteria. Thirteen studies compared acamprosate with placebo, 19 studies compared naltrexone with a control group (placebo or reference group), and one study compared naltrexone with acamprosate. Acamprosate significantly improved abstinence rate and treatment compliance compared with placebo (see http://www.ebmentalhealth.com/supplemental for table). Acamprosate significantly increased the duration of abstinence compared with placebo (weighted mean difference: 27 days; SD 18–36.5 days). Acamprosate produced few side effects. The most common adverse events were gastrointestinal problems. In the short term, naltrexone significantly reduced relapse rate but not abstinence rate compared with controls (see table). Few studies reported the effects of long term naltrexone use. Naltrexone caused frequent side effects, however these did not significantly lower adherence to treatment.
Naltrexone and acamprosate are both safe and effective treatments for alcohol dependence in adults. Acamprosate improves adherence and abstinence rates, whereas naltrexone significantly reduces relapse rates, time to relapse, and frequency of drinking. However, the high level of non-compliance for both treatments may limit their usefulness.
All studies involved some form of psychosocial intervention in combination with naltrexone or acamprosate that varied widely between studies.
Psychosocial treatments offer definite but limited success in the treatment of alcohol dependence. Two adjunctive medications, acamprosate and naltrexone, have been the subject of recent meta-analyses1,3 and reviews4,5 that support a beneficial therapeutic effect. Bouza et al’s meta analysis includes 13 acamprosate studies (n = 4000) and 19 naltrexone studies (n = 3205). In all the acamprosate studies and in 15 of the naltrexone studies, all participants had been detoxified before treatment. Studies were predominantly conducted in ambulatory settings. Study duration ranged from three to 24 months. Only two studies prescribed naltrexone in a fixed dose beyond three months. One study included psychiatric pathology.
The major findings confirm acamprosate raises the continuous abstinence rate with a calculated number needed to treat of 10 (95% CI 7 to 15) and significantly improves cumulative abstinence (doubled in the seven studies that supplied data) both in treatment and follow up period. It may be more useful in therapeutic approaches that target alcohol abstinence. The evidence for naltrexone is less robust (small sample size, studies of short duration). Short term use (12 weeks or less) significantly improves the relapse rate during the active treatment phase with a number needed to treat of 9 (95% CI 6 to 14). Naltrexone treatment trended towards abstinence and seems indicated for programmes that aim to control alcohol consumption. There are insufficient data to establish the superiority of either drug. Only about half of people receiving either medication completed treatment. Compliance figures varied widely (ranging from 40% to 90%). Major areas of uncertainty include the need and type of psychosocial therapy best suited to each drug, the interaction between drug therapeutic profile/patient characteristics, and the optimal duration of treatment.
Although studies mainly use strict selection criteria excluding other comorbidities and dependencies, a profile not seen in the usual clinic, Bouza et al confirm both agents work (although differently) in alcoholism treatment, are safe, and are acceptably tolerated. The findings suggest a different practical application for each drug. These conclusions further endorse the incorporation of these agents into clinical practice. The clinical utility of combining naltrexone and acamprosate has been demonstrated6 implying both compounds may act additively. This awaits confirmation.
Review history and Supplementary material
The table is available as a downloadable PDF (printer friendly file).
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- [View PDF] - Table Effect of naltrexone and acamprosate in people with alcohol dependence
For correspondence: Carmen Bouza, Agency for Health Technology Assessment, Instituto de Salud Carlos III, Sinesio Delgado 4, 28029 Madrid, Spain;
Sources of funding: not stated.