Clinical association between pharmacogenomics and adverse drug reactions

Adverse drug reactions (ADRs) are a major public health concern and cause significant patient morbidity and mortality. Pharmacogenomics is the study of how genetic polymorphisms affect an individual’s response to pharmacotherapy at the level of a whole genome. This article updates our knowledge on how genetic polymorphisms of important genes alter the risk of ADR occurrence after an extensive literature search. To date, at least 244 pharmacogenes identified have been associated with ADRs of 176 clinically used drugs based on PharmGKB. At least 28 genes associated with the risk of ADRs have been listed by the Food and Drug Administration as pharmacogenomic biomarkers. With the availability of affordable and reliable testing tools, pharmacogenomics looks promising to predict, reduce, and minimize ADRs in selected populations.

Antidepressant pharmacogenetics

Purpose of review: This article reviews recent literature published over the period March 2012–August 2013 on antidepressant pharmacogenetics, with a focus on clinical translation and methodological challenges.

Recent findings: Recently, various polymorphisms associated with differential antidepressant efficacy, tolerability, and safety have emerged in association studies, but mixed findings, limited effect sizes, and poor control of confounders have prevented findings translating to practice. Although promising steps have been made, empirically robust clinically translatable pharmacogenetic tests are not yet established. The complex neurobiology of major depressive disorder (MDD) together with the evolving understanding of genetic processes present research challenges for clinical translation.

Summary: Early reports of clinical utility are published. The current evidence base for antidepressant pharmacogenetics is, however, not yet empirically robust enough to inform routine prescribing guidelines. Over the coming years, genetically guided versus unguided trials will help determine if antidepressant pharmacogenetics merits more widespread application.