Pharmacogenomics in the Personalized Therapy of Major Depressive Disorder

Abstract

Major Depressive Disorder (MDD) is the culprit behind significant morbidity and mortality globally, marked by complex etiology, including but not limited to hypothalamic-pituitary-adrenal (HPA) axis dysfunction, neuroinflammation, and genetic susceptibility. The commonplace standard of care relies on a rather empirical "trial-and-error" prescription system that often finds failure or a lack of efficacy, which has paved the way forward for the so-called "Treatment-Resistant (TR) Depression". In response to such, pharmacogenomics provides a personalized framework that seeks to match antidepressant selection to a patient's unique genetic makeup. Polymorphisms among members of the cytochrome family of enzymes help to stratify patients into different metabolizer phenotypes, with drug responses differing based on the phenotype. Despite hurdles such as data scale and complexity, clinical trials reveal an improvement in pharmacogenomic-guided therapy as compared to standard care.