Response to Naltrexone for Alcohol Use Disorder is Not Mediated by an Opioid Receptor Polymorphism

Naltrexone has been shown to be modestly effective for the treatment of alcohol use disorder. Post hoc analyses of previous trials suggest that the response to naltrexone may be mediated by polymorphisms of the mu-opioid receptor gene; specifically, individuals with 1 or 2 copies of the Asp40 allele were more likely not to relapse to heavy drinking with naltrexone treatment. This is the first prospective trial to test the hypothesis that having at least one copy of the Asp40 allele would predict a better response to treatment. In this 12-week trial, 221 individuals with DSM-IV alcohol dependence were stratified by genotype and randomized to naltrexone or placebo.

• There were no significant differences between the groups in demographics or drinking measures.
• For the primary outcome of heavy drinking, there was no significant interaction between genotype and treatment.
• In the group without the Asp40 allele, the odds of heavy drinking in the naltrexone group were 0.69 times those in the placebo group. For those with the Asp40 allele, they were 1.10. Neither difference was statistically significant.

Comments:

Personalized medicine guided by genomics has been touted as the future of health care, but so far it has had limited clinical application. This study suggests that the Asp40 allele does not moderate response to naltrexone and that we cannot use this to guide treatment decisions for individuals with alcohol use disorder.

Darius A. Rastegar, MD

Reference:

Oslin DW, Leong SH, Lynch KG, et al. Naltrexone vs. placebo for the treatment of alcohol dependence: a randomized clinical trial. JAMA Psychiatry. 2015;72(5):430–437.