Abstract
Background
Alcohol dependence belongs to the globally leading health risk factors. Therapeutic success of psychosocial programs for relapse prevention is moderate and could be increased by an adjuvant treatment with the opioid antagonists naltrexone and nalmefene.
Objectives
To determine the effectiveness and tolerability of opioid antagonists in the treatment of alcohol dependence.
Search methods
We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE and CINAHL in January 2010 and inquired manufacturers and researchers for unpublished trials.
Selection criteria
All double-blind randomised controlled trials (RCTs) which compare the effects of naltrexone or nalmefene with placebo or active control on drinking-related outcomes.
Data collection and analysis
Two authors independently extracted outcome data. Trial quality was assessed by one author and cross-checked by a second author.
Main results
Based on a total of 50 RCTs with 7793 patients, naltrexone reduced the risk of heavy drinking to 83% of the risk in the placebo group RR 0.83 (95% CI 0.76 to 0.90) and decreased drinking days by about 4%, MD -3.89 (95% CI -5.75 to -2.04). Significant effects were also demonstrated for the secondary outcomes of the review including heavy drinking days, MD – 3.25 (95% CI -5.51 to -0.99), consumed amount of alcohol, MD – 10.83 (95% CI -19.69 to -1.97) and gamma-glutamyltransferase, MD – 10.37 (95% CI -18.99 to -1.75), while effects on return to any drinking, RR 0.96 (95 CI 0.92 to 1.00) missed statistical significance. Side effects of naltrexone were mainly gastrointestinal problems (e.g. nausea: RD 0.10; 95% CI 0.07 to 0.13) and sedative effects (e.g. daytime sleepiness: RD 0.09; 95% CI 0.05 to 0.14). Based on a limited study sample, effects of injectable naltrexone and nalmefene missed statistical significance. Effects of industry-sponsored studies, RR 0.90 (95% CI 0.78 to 1.05) did not significantly differ from those of non-profit funded trials, RR 0.84 (95% CI 0.77 to 0.91) and the linear regression test did not indicate publication bias (P = 0.765).
Authors’ conclusions
Naltrexone appears to be an effective and safe strategy in alcoholism treatment. Even though the sizes of treatment effects might appear moderate in their magnitudes, these should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment.
Plain language summary
Naltrexone and nalmefene for alcohol dependent patients
Alcohol dependence is a chronic disease, which can develop when alcohol is heavily used over longer periods of time. Alcohol affects various brain regions, including the opioid receptor system, which mediates euphoric and pleasurable effects of alcohol. By blocking alcohol effects at these receptors, the opioid antagonists naltrexone and nalmefene can reduce alcohol “liking” and “craving” and thus support alcohol dependent patients in cutting down their drinking. 50 studies with 7793 participants were included in the review, in most studies treatment was provided over a period of three months. The review shows that more patients who took naltrexone were able to reduce the amount and frequency of drinking than those who took an identical appearing, but inert substance (placebo). On average, one out of nine patients was helped by naltrexone. Naltrexone does not have serious side effects, but gastrointestinal symptoms like nausea, stomach pain and loss of appetite are common. Some patients also get tired from naltrexone. For injectable formulations of naltrexone, which can be advantageous for patients who have problems with taking their medication on schedule, and the second opioid antagonist nalmefene, the database is still too sparse to allow final conclusions. Nevertheless, the available studies indicate that these drugs might have comparable effects on drinking than oral naltrexone has. Naltrexone does not cause dependency and unlike disulfiram, another medicine that is sometimes used to treat alcohol dependence, it does not make patients feel sick if they drink alcohol while taking it.
