From the Origins of Pharmacogenetics to First Applications in Psychiatry

Abstract

Pharmacogenetics is the division of science addressing how genetic factors contribute to the metabolism, response, and side effects of a given medication. What was once regarded as a subdivision of genetics and pharmacology is now recognized as its own field and has its own unique story of origin. While the term “pharmacogenetics” was coined by Friedrich Vogel in 1959, the relevance of inherited genetic traits in affecting the clinical outcome to xenobiotics has been observed long before. In fact, there is much hope that pharmacogenetics can help unravel the “mysteries” as to why different people may display variable responses to the same medication as well as identify new drug targets. This article will highlight the conceptual framework for pharmacogenetics advanced by pioneer scientists Arno Motulsky and Friedrich Vogel (both human geneticists), as well as Werner Kalow (clinical pharmacologist), leading up to the creation of modern pharmacogenetics. Finally, the practical implications and first steps toward implementation for current psychiatric treatment are reviewed followed by an outlook on future studies.

Review and Consensus on Pharmacogenomic Testing in Psychiatry

“…1 Only guidelines where a clinical action has been recommended were included. 2 Product label information was extracted from the Pharmacogenomics Knowledgebase (PharmGKB), only labels coded as "actionable," "test recommended," or "test required" by PharmGKB curators were included. For a description of these categories (PGx levels) and the drug label curation process, see https://www.pharmgkb.org/page/drugLabelLegend.…”

“…Yet the same dose may not be the correct one for all individuals. Another emerging and complementary strategy is the implementation of pharmacogenomic (PGx) testing to inform medication selection and dosing decisions [2]. PGx testing examines genetic variation involved in medication metabolism and action to facilitate individualized prescribing, thus reducing undesirable outcomes.…”

“…Clinical Pharmacogenetics Implementation Consortium; DPWG: Dutch Pharmacogenetics Working Group; EMA: European Medicines Agency; FDA: US Food and Drug Administration; HCSC: Health Canada (Santé Canada); PMDA: Pharmaceuticals and Medical Devices Agency, Japan 1. Only guidelines where a clinical action has been recommended were included 2. Product label information was extracted from the Pharmacogenomics Knowledgebase (PharmGKB), only labels coded as "actionable," "test recommended," or "test required" by PharmGKB curators were included.…”

“…Only guidelines where a clinical action has been recommended were included 2. Product label information was extracted from the Pharmacogenomics Knowledgebase (PharmGKB), only labels coded as "actionable," "test recommended," or "test required" by PharmGKB curators were included.…”

Pharmacogenetics in Psychiatry

“…The first article by Müller & Rizhanovsky [1], illuminates how ancient scientists such as Pythagoras, already addressed challenges of inter-individual variability observed in people who consumed fava beans. While unaware of the molecular genetic causes, heritability factors were long suspected and first proven for heritable alkaptonuria by Garrod in the early 20 th century.…”