Naltrexone is a non-selective antagonist of mu, kappa, and delta opioid receptors that was initially approved to treat opioid dependence. By reducing mesolimbic opioidergic activity and thereby modulating the dopamine-mediated rewarding effects of alcohol, it reduces alcohol consumption. Two initial 12-week RCTs in which naltrexone 50 mg/day or placebo was initiated after patients achieved a period of abstinence led to the FDA’s approval of that dosage for treating alcohol dependence.49,50 A meta-analysis supports naltrexone’s efficacy in reducing both the risk of relapse to any drinking [16 studies; N=2,347; risk decrease (RD)= −0.05 (95%CI= −0.10 to −0.002); number needed to treat (NNT)=20] or a return to binge drinking [19 studies; N=2,875; RD= −0.09 (95% CI= −0.13 to −0.04); NNT=12).11 Both associations, though statistically significant, are modest in magnitude, which has limited the use of naltrexone for treating AUD.39
