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The review describes evidence to support the role of two metabolizing genes—cytochrome P450 2D6 (CYP2D6), known to metabolize fluoxetine, paroxetine, and venlafaxine; and cytochrome P450 2C19 (CYP2C19), known to metabolize citalopram and escitalopram—in the response of patients to antidepressants.
“The evidence-based rationale for CYP2D6 or CYP2C19 genetic testing can be delineated by serum levels, lower tolerability, serious adverse events (blood pressure changes, QT prolongation, seizures, and death), and pharmacogenetics-based primary outcome measures (e.g., antidepressant response),” the authors wrote.
The authors described ways that the results of CYP2D6 or CYP2C19 genetic tests might be used to aid clinicians in the selection of antidepressants: “For example, when prescribing fluoxetine, paroxetine, or venlafaxine to a patient who is a known CYP2D6 poor or poor-to-intermediate metabolizer or prescribing citalopram or escitalopram to a patient who is a known CYP2C19 poor or poor-to-intermediate metabolizer, an alert will appear on the computerized physician order entry system. In the absence of clear FDA guidelines for dose adjustment, an alternative medication that is metabolized by another enzyme should be considered.”
“With the continuous decrease in the cost of genetic testing, the willingness of insurance companies to cover such tests, and the increase in published data providing more robust evidence of clinical importance, CYP2D6/CYP2C19 genotyping might become, in the near future, a routine test before prescribing relevant antidepressants to all patients,” the authors concluded.
“Genetic and other laboratory … tests will increasingly be used in psychiatry over the coming years, and practitioners today need to understand the principles outlined here to be able to utilize these tools in an informed way in the treatment of patients,” Sheldon Preskorn, M.D., of the University of Kansas School of Medicine, wrote in a related editorial. “Nissan et al. have provided a review of the rationale for this inevitability and have presented an algorithm to aid in the selection of antidepressants for patients in whom the genetic information needed is already known.”
The Mayo Clinic has a financial interest in Assurex Health Inc. and the technology referenced in this article. Other support came in part from NIMH, NIAAA, and NIH.
(Image: The Biochemist Artist/Shutterstock)
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