Natalia Stollarova

Introduction Discontinuation of psychotropic medication is associated with considerable clinical challenges, including withdrawal symptoms and relapse. Pharmacogenomic testing is increasingly used in clinical practice to optimise pharmacotherapy by guiding drug selection and dosing, however, its role in informing medication discontinuation and tapering strategies remains underexplored. Understanding the influence of genetic variability on withdrawal symptoms could support safer, individualised discontinuation practices. Objective This scoping review aims to map the available evidence on the role of pharmacogenomics on the discontinuation of psychotropic medications. Methods The review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and reported using the PRISMA-ScR checklist. Comprehensive searches will be performed in MEDLINE, EMBASE, CINAHL, Web of Science, and PsycINFO. Studies exploring gene polymorphisms relevant to the discontinuation of psychotropic medications (antidepressants, antipsychotics, mood stabilisers, anxiolytics, hypnotics, stimulants, and opioids) will be considered. Following screening, data will be extracted, and a narrative synthesis will be undertaken to map characteristics of included studies, genes studied, medication classes involved, reported outcomes, and knowledge gaps. Conclusion This review will provide an overview of existing evidence and identify gaps regarding the role of pharmacogenomics in psychotropic medication discontinuation. The findings will help to inform future research on the integration of pharmacogenomics into individualised tapering strategies.

Introduction Discontinuation of psychotropic medication is associated with considerable clinical challenges, including withdrawal symptoms and relapse. Pharmacogenomic testing is increasingly used in clinical practice to optimise pharmacotherapy by guiding drug selection and dosing, however, its role in informing medication discontinuation and tapering strategies remains underexplored. Understanding the influence of genetic variability on withdrawal symptoms could support safer, individualised discontinuation practices. Objective This scoping review aims to map the available evidence on the role of pharmacogenomics on the discontinuation of psychotropic medications. Methods The review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews and reported using the PRISMA-ScR checklist. Comprehensive searches will be performed in MEDLINE, EMBASE, CINAHL, Web of Science, and PsycINFO. Studies exploring gene polymorphisms relevant to the discontinuation of psychotropic medications (antidepressants, antipsychotics, mood stabilisers, anxiolytics, hypnotics, stimulants, and opioids) will be considered. Following screening, data will be extracted, and a narrative synthesis will be undertaken to map characteristics of included studies, genes studied, medication classes involved, reported outcomes, and knowledge gaps. Conclusion This review will provide an overview of existing evidence and identify gaps regarding the role of pharmacogenomics in psychotropic medication discontinuation. The findings will help to inform future research on the integration of pharmacogenomics into individualised tapering strategies.

This study is designed to address the connection between antidepressant and antipsychotic-induced hepatotoxicity with pharmacogenetic and epigenetic indicators, using a novel combined approach of CYP450 polymorphism determination and early liver injury detection via microRNA testing. The multi-centric retrospective case-control study in Slovakia involves 151 cases with signs of hepatotoxicity and 604 controls without. Participants will be tested for selected CYP450, UGT1A1 polymorphisms, and microRNAs. Anticipated findings will test if patients with specific CYP450 and UGT1A1 polymorphisms are at higher risk for drug-induced hepatotoxicity and if plasma microRNAs hsa-miR-122-5p and hsa-miR-192-5p, alone or combined, can differentiate patients with abnormal liver function. The findings could contribute to personalized treatment approach by combining genetic and epigenetic biomarkers.

Determining variant TPMT alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the TPMT-adjusted thiopurine dosing, some TPMT wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene NUDT15 has emerged as a significant co-modulator of thiopurine therapy. Initially, NUDT15 was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well.To evaluate the pharmacogenetic significance of NUDT15 in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia.We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for NUDT15*3, were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.