A cross-sectional study of the relationship between CYP2D6 and CYP2C19 variations and depression symptoms, for women taking SSRIs during pregnancy.

Abstract

Depression during pregnancy affects 10-15% of women, and 5% of women take antidepressants during pregnancy. Clinical guidelines provide recommendations for selective serotonin reuptake inhibitor (SSRI) drug choice and dose based on CYP2D6 and CYP2C19 genotype; however, they are based on evidence from non-pregnant cohorts. This study aimed to test the hypothesis that women with function-altering variants (increased, decreased, or no function) in these pharmacogenes, taking SSRIs prenatally, would have more depression symptoms than women whose pharmacogenetic variants are associated with normal SSRI metabolism. Comprehensive CYP2D6 and CYP2C19 genotyping using a range of methods, including gene copy number analysis, was performed as secondary analyses on two longitudinal cohorts of pregnant women (N= 83) taking the SSRIs paroxetine, citalopram, escitalopram, or sertraline. The Kruskal-Wallis test compared mean depression scores across four predicted metabolizer groups: poor (n= 5), intermediate (n= 10), normal (n= 53), and ultrarapid (n= 15). There were no significant differences between mean depression scores across the four metabolizer groups (H(3) = .73, p= .87, eta-squared = .029, epsilon-squared = .0089). This is the first study of the relationship in pregnancy between CYP2C19 pharmacogenetic variations and depression symptoms in the context of SSRI use. Findings from this initial study do not support the clinical use of pharmacogenetic testing for SSRI use during the second or third trimesters of pregnancy, but these findings should be confirmed in larger cohorts. There is an urgent need for further research to clarify the utility of pharmacogenetic testing for pregnant women, especially as companies offering direct-to-consumer genetic testing expand their marketing efforts.