On the Marketing and Use of Pharmacogenetic Tests for Psychiatric Treatment

摘要

Clinicians hope to see translational uses of powerful new technologies, such as brain imaging and genomic testing, guiding care of patients. In genomics, many newly risen companies promise to address this hope by vigorously marketing pharmacogenetic (Pgen) tests, especially for the treatment of major depressive disorder (MDD). One company’s website reports sales of over 650?000 Pgen tests.~(1) Does the evidence support such use? The heterogeneous and complex underlying causes and mechanisms of illness and clinical response to treatment in MDD strongly suggest that there will be serious issues limiting or preventing the development of Pgen approaches to treatment choice. Simply put, MDD is determined by a large number of genes, and, except in rare cases, no single gene or limited gene set, even those for drug metabolism and drug targets, determines more than a few percent of the risk of illness or course of treatment.~(2)~(-4) Environmental factors (age, sex, diet, alcohol use, hormonal status, general health) and comedication are usually more important factors than inherited determinants of drug metabolism and response.~(5) While the activity of metabolic enzymes is heritable, extremely rapid or slow metabolism is rare, and dosing needn't be guided by Pgen rather than by careful dose choice and monitoring therapeutic and adverse effects.~(6) Thus, the available evidence suggests that Pgen tests will not contribute much to care.