CYP2C19 Genotyping Aids Risk Stratification, Individualized Therapy for Depression

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Escitalopram is metabolized in the hepatic cytochrome P450 pathway by enzyme <i>CYP2C19</i>.
Escitalopram is metabolized in the hepatic cytochrome P450 pathway by enzyme CYP2C19.

Genotyping patients for CYP2C19 may assist in determining risk for escitalopram treatment failure and aid in designing an individualized approach to antidepressant dosing, according to findings from a retrospective study published in the American Journal of Psychiatry.

Using the drug monitoring database at Diakonhjemmet Hospital in Oslo, Norway, investigators collected 4228 escitalopram serum concentration measurement data from CYP2C19-genotyped patients (n=2087). Serum concentrations were recorded approximately 10 to 30 hours following drug intake. Investigators compared drug metabolism and subsequent treatment success/failure among individuals carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. Treatment failure with the escitalopram was defined as switching to another antidepressant <1 year following the last escitalopram serum concentration measurement.

Escitalopram serum concentrations were increased by 3.3-fold among CYP2C19Null/Null participants vs those in the CYP2C19*1/*1 group. Additionally, serum concentrations were 1.6-fold and 1.4-fold in the CYP2C19*Null/*1 and CYP2C19Null/*17 groups, respectively. Additionally, a 10% and 20% decrease in serum escitalopram concentrations was observed in the CYP2C19*1/*17 and CYP1C19*17/*17 group, respectively. Treatment failure was 3.3 times more frequent in the CYP2C19Null/Null, 1.6 times more frequent in the CYP2C19*1/*17 group, and 3.0 times more frequent in the CYP1C19*17/*17 group.

The investigators were unable to obtain data on patients' diagnosis and treatment outcomes at blood sampling, despite having data on treatment switching. In addition, the investigators were unable to determine the cost-benefit ratio of CYP2C19 genotyping in this patient population, a finding that may influence its applicability in clinical practice.

Overall, the results of this study suggest “preemptive CYP2C19 genotyping could prospectively be of value for the individualization of escitalopram dosing, resulting in increased drug efficacy and fewer cases of drug switching.”

Reference

Jukić MM, Haslemo T, Molden E, Ingelman-Sundberg M. Impact of CYP2C19 genotype on escitalopram exposure and therapeutic failure: a retrospective study based on 2,087 patients [published online January 12, 2018]. Am J Psychiatry. doi:10.1176/appi.ajp.2017.17050550

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