Opioid antagonists for alcohol dependence

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 Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials.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.