266. <i>OPRM1</i> A118G POLYMORPHISMS AND NALTREXONE TREATMENT RESPONSE AMONG TAIWANESE PATIENTS WITH ALCOHOL USE DISORDER

Abstract Background Alcohol is recognized as one of the most harmful addictive substances, contributing significantly to both mental and physical impairment. Alcohol Use Disorder (AUD) has a high lifetime prevalence, posing a substantial public health challenge. Among the available treatments, naltrexone is commonly used; however, its efficacy in managing AUD remains controversial. One key factor influencing treatment outcomes is the OPRM1 A118G polymorphisms. Notably, most previous research has predominantly focused on Caucasian populations, yielding inconsistent findings. Aims &amp; Objectives We focused on investigating how the OPRM1 A118G polymorphisms moderated naltrexone treatment response in Taiwanese patients with alcohol use disorder after detoxification. The study aimed to address the gap with research focusing on Asian populations, particularly individuals of Han Taiwanese descent. We followed treatment-seeking patients over 12 weeks to evaluate their progress, considering the high frequency of the G allele (40-50%) in Asian populations and its potential impact on naltrexone efficacy. Method The study was conducted at the Department of Addiction Sciences, Taipei City Psychiatric Center, following Good Clinical Practice Guidelines and the Declaration of Helsinki. A total of treatment-seeking Taiwanese Han patients with severe AUD were recruited. Patients underwent detoxification, followed by 12 weeks of naltrexone treatment, with doses titrated from 25 mg/d to 50 mg/d. Assessments occurred at baseline and at weeks 4, 8, and 12, measuring variables such as alcohol cravings, relapse rates, psychological symptoms, and biochemical markers. Genotyping for OPRM1 A118G polymorphisms was performed using TaqMan SNP Genotyping Assays. Data were analyzed using descriptive statistics, Chi-square tests, Fisher’s exact tests, t-tests, and Generalized Estimation Equations. Results The A/A genotype group and the G allele carrier genotype group (A/G + G/G) consisted of 83 and 92 participants, respectively. The age of first alcohol consumption was significantly older in the G allele carrier group compared to the A/A genotype group (19.5 ± 9.4 vs. 18.0 ± 9.8 years, p &amp;lt; 0.05). Regarding drinking outcomes, significant time effects were observed in both genotype groups (p &amp;lt; 0.01). The G allele carrier group demonstrated better drinking outcomes than the A/A genotype group, with fewer maximum drinks per day and more abstinent days per week (p &amp;lt; 0.05). Additionally, significant time effects were identified for psychological outcomes, including depressive symptoms, anxiety symptoms, and alcohol craving, in both genotype groups. Notably, alcohol craving among G allele carriers showed a more pronounced and significant decrease compared to the A/A genotype group. Furthermore, depressive symptoms in the G allele carrier group (A/G + G/G) decreased significantly faster than in the A/A genotype group, particularly by week 4. Discussion &amp; Conclusions Naltrexone treatment significantly reduced drinking and psychological symptoms in Taiwanese AUD patients, with G allele carriers showing more pronounced improvements in craving compared to A/A genotype carriers. Naltrexone treatment reduced depressive symptoms faster in G allele carriers compared to A/A genotype carriers. The study suggests the potential for precision treatment with naltrexone based on OPRM1 A118G polymorphisms in patients with AUD in Asian.