Gual 2013 (ESENSE 2): as-needed nalmefene to cut drinking

What they tested

718 adults with alcohol dependence were randomly given nalmefene 18 mg (358 people) or placebo (360 people) to take as needed for 24 weeks. Nalmefene is an opioid blocker closely related to naltrexone.

To join, people had to have at least 6 heavy drinking days and drink at or above the World Health Organization's medium-risk level in the 4 weeks before screening. The two main measures were the change in heavy drinking days and in total alcohol consumption by month 6.

What they found

By month 6, people on nalmefene had 1.7 fewer heavy drinking days a month than people on placebo, a statistically significant difference (p=0.012).

Total drinking fell by 5.0 g a day more on nalmefene, but that difference was not statistically significant (p=0.088).

In a subgroup analysis, patients who had not reduced their drinking before randomization got more benefit from nalmefene. Clinical Global Impression ratings, a clinician's overall judgment of how a patient is doing, and liver enzymes improved more on nalmefene.

Side effects were more common with nalmefene, but about as many people in each group dropped out because of them.

Limits

• One of its two main outcomes, total alcohol consumption, didn't reach statistical significance.
• The bigger benefit in people who hadn't cut down came from a subgroup analysis, not from the main comparison.
• It tested nalmefene, not naltrexone, at a fixed 18 mg dose taken as needed.

What it means if you're considering naltrexone

Nalmefene isn't naltrexone, but it's a close chemical cousin, and this trial is one of the main tests of taking an opioid blocker as needed to drink less rather than to quit. That is a similar idea to the Sinclair Method, which uses naltrexone. The result was a drop of 1.7 heavy drinking days a month compared with placebo, while the effect on total drinking fell short of significance.

The site's nalmefene guide notes that the European Union authorised nalmefene (Selincro) for alcohol dependence in 2013, and that in the US nalmefene is a prescription medicine for reversing opioid overdoses.