A review of the existing pharmacogenomic literature of naltrexone for use in alcohol use disorder

Naltrexone is an opioid receptor antagonist used to treat alcohol use disorder; however, like other commonly used addiction treatment options, it demonstrates inconsistency in treatment response. Pharmacogenomics may be used to individualize addiction treatment and identify patients who would be better candidates for this drug. Recently, the Clinical Pharmacogenomics Implementation Consortium (CPIC) provided guidelines on pharmacogenomic testing for naltrexone. Pharmacogenomic testing targets for naltrexone include pharmacodynamic genes, like the mu-opioid receptor gene <i>OPRM1</i>, as well as pharmacokinetic genes, like alcohol and aldehyde dehydrogenase (<i>ADH</i> and <i>ALDH</i>, respectively). In this article, we review the studies investigating the genotypes associated with either substance craving, intoxication effect, or relapse in patients receiving naltrexone to treat alcohol addiction. A common single nucleotide polymorphism (SNP) in OPRM1 called rs1799971 has been found to contribute to an improved naltrexone response in some studies. However, prospective genotype-stratified trials and meta-analyses have failed to confirm a clinically significant moderating effect. While not as studied as <i>OPRM1</i>, alcohol metabolizing enzymes, <i>ALDH2</i> and <i>ADH1B</i>, may also contribute to naltrexone response. Current evidence does not support clinical implementation of genotyping for naltrexone prescribing decisions; however, further research on the pharmacogenomics of naltrexone is warranted.