2026 ECNP Congress

S21.03

Pharmacogenomics of treatment resistance: challenges, pitfalls and new perspectives

Alessandra Minelli — University of Brescia, Department of Molecular and Translational Medicine, Brescia, Italy

2026 ECNP Congress

Prof. Alessandra Minelli’ presentation will focus on pharmacogenetics and pharmacogenomics as tools to understand how genetic variability influences antidepressant response, non-response, and treatment resistance (TR) in major depressive disorder (MDD). MDD is a heterogeneous disorder, and approximately one third of patients develop TR, highlighting the need for personalized treatment. Individuals with early non-response are often managed through trial-and-error due to the lack of reliable predictors of TR and limited translation of scientific findings.

Pharmacogenetics and pharmacogenomics provide a framework to explain interindividual differences in antidepressant efficacy and tolerability. Variants in pharmacokinetic genes, particularly those encoding cytochrome P450 enzymes (CYP2D6 and CYP2C19), influence drug metabolism and risk of adverse effects. Altered metabolic capacity results in subtherapeutic drug levels or increased side effects, contributing to non-response, poor adherence, and TR. Pharmacogenetic tests aim to guide drug selection and dosing based on genetic variability, potentially improving response rates and reducing adverse effects.

Prof. Minelli will present the latest findings from randomized controlled trials evaluating pharmacogenomic-based decision support tools for antidepressant treatment in real-world settings. She will also discuss recent results from the PANDORA pharmacogenomic project, characterized by broad recruitment and detailed clinical phenotyping, which is expected to provide important findings and future directions for safer and more effective treatments pharmacological treatments for MDD. Additionally, she will discuss the latest findings from pharmacogenomic trials and their relevance for optimizing pharmacological treatments. Integrating pharmacogenetic and pharmacogenomic into practice represents a promising step toward predicting response, identifying TR risk, and advancing precision psychiatry in MDD.