Frequencies of CYP2C19 and CYP2D6 gene variants in a German inpatient sample with mood and anxiety disorders

Abstract

Objectives

Previous results demonstrated that CYP2D6 and CYP2C19 gene variants affect serum concentrations of antidepressants. We implemented a PGx service determining gene variants in CYP2D6 and CYP2C19 in our clinical routine care and report on our first patient cohort.

Methods

We analysed CYP2D6 and CYP2C19 allele, genotype, and phenotype frequencies, and actionable pharmacogenetic variants in this German psychiatric inpatient cohort. Two-tailed z-test was used to investigate for differences in CYP2D6 and CYP2C19 phenotypes and actionable/non-actionable genetic variant frequencies between our cohort and reference cohorts.

Results

Out of the 154 patients included, 44.8% of patients were classified as CYP2D6 normal metabolizer, 38.3% as intermediate metabolizers, 8.4% as poor metabolizers, and 2.6% as ultrarapid metabolizers. As for CYP2C19, 40.9% of patients were classified as normal metabolizers, 19.5% as intermediate metabolizers, 2.6% as poor metabolizers, 31.2% as rapid metabolizers, and 5.8% as ultrarapid metabolizers. Approximately, 80% of patients had at least one actionable PGx variant.

Conclusion

There is a high prevalence of actionable PGx variants in psychiatric inpatients which may affect treatment response. Physicians should refer to PGx-informed dosing guidelines in carriers of these variants. Pre-emptive PGx testing in general may facilitate precision medicine also for other drugs metabolised by CYP2D6 and/or CYP2C19.

Keywords:

• Routine clinical care
• pharmacogenetic testing
• psychiatry
• CYP2D6
• CYP2C19

Acknowledgements

None.

Statement of interest

J. Deckert and H. Weber receive funding from the Deutschen Zentrum für Luft- und Raumfahrt (DLR) - Förderkennzeichen 01EK2204G (P4D, Project SP1, SP5A and Coordination). D. Müller has received research grants from CAN-BIND, Canadian Institutes of Health Research, Nubiyota, Ontario Brain Institute, CAMH AFP Innovation Funds and the CAMH Foundation. M. Scherf-Clavel, and S. Unterecker have no conflicts of interest.