Pharmacogenetics and Psychiatric Care: A Review and Commentary

Abstract

Personalized or precision medicine is emerging in the treatment of human diseases and management based on each individual’s genetic pattern and response to drugs categorized into two areas: 1) pharmacogenetics and 2) pharmacogenomics1–5. Pharmacogenetics is the study of DNA structural variations and impact on drug metabolism, efficacy and tolerability. DNA remains stable and does not change with time or age. Pharmacogenetics is most often based on the cytochrome P450 enzyme system, primarily found in the liver and involves genes coding for the production of cytochrome P450 enzymes6–9. The response to medications depends on each individual’s ability to metabolize drugs with most drugs broken down by this enzyme system dependent on the genetic makeup of each person. Pharmacogenomics is the study of DNA and RNA characteristics impacting gene function but can change or be influenced by factors (e.g., environment)10–12. Hence, pharmacogenetics deals with single genes and their structure while pharmacogenomics relates to gene function influenced by the environment, both can play a role in human disease including drug metabolism. The Federal Drug Administration (FDA) and National Institutes of Health (NIH) have identified pharmacogenetics and pharmacogenomics as important key tools in development and testing of new drugs and their impact in treating individuals with human disease10,13,14. Inter-individual variability in drug response is now recognized as a major clinical problem in westernized societies where polymedication is common. Relevant gene polymorphisms with different racial distributions are identified sources of variability in drug responses by the modulation of drug-metabolizing cytochrome P450 enzymes discussed in this report. The conceptualization of drug interaction and potential relationship to an individual’s ability to break down drugs or metabolism influenced by genetics was raised by Motulsky in 195715,16 and later supported by genetic-based pharmacokinetics research. For several years, it was known that certain anesthetic agents and doses would be altered depending on the individual’s response, signs and symptoms during surgical procedures when anesthesia was administered indicating variable responses from person to person possibly related to differences in their genetic patterns.