Mann 2013 (ESENSE 1): as-needed nalmefene cut heavy drinking

What they tested

604 adults with alcohol dependence were randomly assigned in equal numbers to nalmefene 18 mg (306 people) or placebo (298 people), to be taken as needed for 24 weeks. Nalmefene is an opioid blocker closely related to naltrexone.

Everyone had at least 6 heavy drinking days and drank at or above the World Health Organization's medium-risk level in the 4 weeks before screening. The efficacy analysis included 290 people on nalmefene and 289 on placebo.

What they found

At month 6, nalmefene beat placebo on both main measures: 2.3 fewer heavy drinking days (p = .0021) and 11.0 g a day less total alcohol (p = .0003).

Clinical Global Impression ratings, a clinician's overall judgment of how a patient is doing, and liver enzymes improved more on nalmefene by week 24.

Side effects, mostly mild or moderate, were more common on nalmefene, and so were dropouts because of side effects. The number of people with serious side effects was similar in the two groups.

Limits

• The trial aimed at cutting down, not quitting, so it doesn't show whether nalmefene helps people stay abstinent.
• More people on nalmefene dropped out because of side effects.
• It tested nalmefene, not naltrexone, and lasted 24 weeks.

What it means if you're considering naltrexone

ESENSE 1 and its sister trial ESENSE 2 are the two six-month trials the site's nalmefene guide uses for as-needed nalmefene. For someone weighing naltrexone, the trial matters because it tests an idea similar to the Sinclair Method (an opioid blocker used to cut down rather than to quit), though with nalmefene rather than naltrexone. The site's Sinclair Method guide notes that UK guidance on nalmefene does not endorse the Sinclair Method itself.