Personalizing Treatment for Acute Alcoholic Hallucinosis: Clinical Utility of Integrated Pharmacogenetic Testing,...

Acute alcoholic hallucinosis (ICD-10 F10.52) necessitates urgent antipsychotic treatment but carries high risks of adverse drug reactions (ADRs). While pharmacogenetic clinical decision support systems (CDSS) show promise, their utility is limited by static genotyping and incomplete biomarker integration.

This study aimed to develop and validate a multi-omics framework integrating pharmacogenetic testing, CYP phenotyping, and microRNA biomarkers to personalize antipsychotic therapy and improve outcomes in acute alcoholic hallucinosis.

In this three-arm study, 300 Russian inpatients with acute alcoholic hallucinosis underwent: 1) Randomized pharmacogenetic-guided vs. standard therapy (n = 100); 2) CYP2D6/CYP3A4 phenotyping via urinary pinoline/cortisol ratios (n = 100); and 3) microRNA quantification (miR-27b, miR-370-3p; n = 100). Efficacy (PANSS) and safety (UKU) were assessed over 6 days.

Pharmacogenetic guidance significantly reduced ADRs (UKU day 6: 5.0 [3.0 - 8.0] vs. 12.0 [10.0 - 16.0], p < 0.01) with comparable efficacy (PANSS≈1.0). Phenotyping identified 28% CYP2D6 poor metabolizers (vs. 15% by genotyping), exhibiting 40% higher haloperidol levels (r = 0.72, p < 0.001). Baseline miR-27b inversely correlated with day-3 PANSS (r = - 0.54, p < 0.001), while miR-370-3p predicted poorer day-6 response (ΔPANSS r = 0.48, p < 0.001) and higher UKU scores (r = 0.52, p < 0.001). Integrating microRNAs with phenotyping improved ADR prediction accuracy by 22% versus single modalities.

A multi-omics approach synergistically optimizes antipsychotic therapy by addressing genotyping limitations through dynamic phenotyping and microRNA-based prognostication, significantly enhancing safety in this high-risk population.