Current treatments for alcohol dependence, aiming to keep patients abstinent, have shown limited treatment and success rates. Reduction of alcohol consumption is increasingly recognised as a valid and needed option that should be an integrated part of the management of alcohol-dependent patients.

The main objective was to evaluate the efficacy of as-needed use of nalmefene 18 mg (base) versus placebo in reducing the monthly number of heavy drinking days (HDDs) and the monthly total alcohol consumption (TAC; g/day) over 24 weeks in alcohol-dependent patients.

Drinking measures were derived from daily drinking estimates collected with the Timeline Followback method. Safety and additional efficacy data were collected throughout the study.

A total of 604 patients (mean age 51.6 ± 9.6 years, 67% men) were randomised (298 to placebo and 306 to nalmefene). There was a significantly superior effect (mixed model repeated measures) of nalmefene compared to placebo in reducing the number of HDDs (−2.3 ± 0.8 [95% CI −3.8; −0.8]; p = 0.002) and TAC (−11.0 ± 3.0 [95% CI −16.8; −5.1]; p < 0.001). Improvements in Clinical Global Impression - Global Improvement and Severity of Illness scores and reductions in liver enzymes gamma-glutamyltransferase and alanine aminotransferase from baseline were statistically significantly larger in the nalmefene group compared to placebo at week 24. Adverse events (generally transient; most were mild or moderate) and withdrawals were more common with nalmefene than placebo.

Nalmefene was efficacious in reducing alcohol consumption. Nalmefene was safe and well tolerated and dosing on an as-needed basis was feasible.