Genetic Influence on Extended-Release Naltrexone Treatment Outcomes in Patients with Opioid Use Disorder: An...

Area of Science:

• Pharmacogenetics
• Addiction Medicine
• Neuroscience

Background:

• Treatment outcomes for extended-release naltrexone (XR-NTX) in opioid use disorder (OUD) are variable and not fully understood.
• The influence of genetic factors on XR-NTX efficacy requires further investigation.

Purpose of the Study:

• To explore the association between catechol-O-methyltransferase (COMT) rs4680 and mu-opioid receptor (OPRM1) rs1799971 genotypes and XR-NTX treatment outcomes.
• To assess the impact of these genotypes on treatment retention, relapse rates, opioid use frequency, and craving in patients with OUD.

Main Methods:

• A 24-week, open-label, prospective study involving 138 patients with OUD receiving monthly intramuscular XR-NTX.
• Genotyping for COMT rs4680 (n=88) and OPRM1 rs1799971 (n=86) was performed.
• Survival analyses and linear mixed models were used to analyze treatment outcomes.

Main Results:

• Patients with the heterozygous COMT rs4680 Met/Val genotype demonstrated a significantly lower likelihood of relapse to opioids compared to those with the Met/Met genotype.
• No significant association was found between OPRM1 rs1799971 genotype and XR-NTX treatment outcomes.
• Treatment retention, days of opioid use, and opioid cravings were also assessed in relation to genotypes.

Conclusions:

• The COMT rs4680 Met/Val genotype is associated with a reduced risk of opioid relapse, suggesting potential for improved XR-NTX treatment benefit in these patients.
• The OPRM1 rs1799971 polymorphism did not show a significant association with the studied treatment outcomes.
• Larger studies incorporating additional genetic variants and outcomes are recommended to further elucidate pharmacogenetic influences on OUD treatment.