Hartwell 2020: the OPRM1 gene doesn't clearly predict naltrexone response

What they tested

People differ a lot in how well naltrexone works for drinking. One idea is that a common variant in the mu-opioid receptor gene, OPRM1, called Asn40Asp (rs1799971), makes some people more likely to respond. Naltrexone works by blocking opioid receptors.

The researchers searched for placebo-controlled randomized trials that looked at this variant and naltrexone for heavy drinking or alcohol use disorder. They pooled them in a meta-analysis, which combines the results of many trials, and tested whether people carrying the Asp40 version did better on five measures: relapse to heavy drinking, abstinence, percentage of heavy drinking days, percentage of days abstinent and drinks per day.

What they found

Seven trials met the criteria. The authors judged the overall risk of bias as low and found no sign of publication bias, the tendency for positive studies to get published more often.

Of the five drinking outcomes, the gene variant made a difference only for drinks per day, and a small one (d = -0.18, P = 0.02). Once the analysis allowed for testing several outcomes at once, that result was no longer statistically significant.

The variant showed no significant effect on relapse to heavy drinking, abstinence, heavy drinking days or days abstinent.

Limits

• Only seven trials had the genetic data needed, so the evidence is still limited.
• It asks whether one gene variant changes naltrexone's effect, not whether naltrexone works, so it says nothing either way about naltrexone's overall benefit.

What it means if you're considering naltrexone

No genetic test can yet tell someone in advance whether naltrexone will work for them, and this review is one reason. For now, the way to find out is to take it and check progress with a prescriber.