Magnus Ingelman-Sundberg, PhD; BSc.Med is Senior Professor of Molecular Toxicology and research group leader in Pharmacogenetics at the Department of Physiology and Pharmacology , Karolinska Institutet since 2006. He has more than 450 original papers, 24 500 citations (32 000 in Google Scholar) and an h-factor of 85 (ISI) or 105 (Google Scholar). He was a member of The Nobel Assembly at Karolinska Institutet 2008-2018, a Highly cited researcher 2014-2017 and a member of Editorial Advisory Boards of e.g. Trends in Pharmacological Sciences (Edit Board), Pharmacogenetics and Genomics, Pharmacogenomics, Drug Metabolism Reviews, Drug Metabolism and Disposition, Human Genomics. His research focuses on genetics, polymorphism, regulation, function and toxicology of the hepatic ADME system with aims at understanding interindividual differences in drug response. Furthermore he develops novel hepatic in vitro systems for studying liver function and validation of drug targets. Further info see: Trends Pharmacol Sci. 2015; 36:65-7 or Basic Clin Pharmacol Toxicol, 123, 643-644 Dec 2018.
Pharmacogenomics in medicine and psychiatry: current status, limitations and promise
The genomic inter-individual heterogeneity remains a signiﬁcant challenge for both clinical decision-making and the design of clinical trials. Major reasons are the paucity of sufﬁciently powered trials that can quantify the added value of pharmacogenetic testing and the considerable pharmacogenetic complexity with millions of rare variants with unclear functional consequences. The resulting uncertainty is reﬂected in inconsistencies of pharmacogenomic drug labels in Europe and the United States. However recent studies encompassing a very large number of patients have revealed that genotyping of genes encoding enzymes active in the metabolism of neuroactive drugs can provide useful information regarding the dosing of antidepressant and antipsychotic drugs for optimization of efficacy. For the future is appears that high-throughput experimental characterization of pharmacogenomic variants combined with novel computational tools hold promise to improve the accuracy of drug response predictions. Furthermore, an increased application of large biobanks of therapeutic drug monitoring data allows to conduct high-powered retrospective studies that can validate the clinical importance of genetic variants. The translation of pharmacogenomic knowledge into clinical practice can indeed be considered for many CNS drugs, but this requires education of clinicians, instructive guidelines, as well as full attention to polypharmacy and other clinically relevant factors. To further judge the clinical and financial benefits of pre-emptive genotyping in psychiatry, large prospective randomized trials are needed to quantify the value of genetic-based patient stratification and to demonstrate the cost-effectiveness of such interventions. The lecture will give an update of the field and provide examples on useful pre-emptive genotyping for more effective drug treatment in psychiatry.
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