Clinical implications of selective serotonin reuptake inhibitors-selective serotonin norepinephrine reuptake inhibitors pharmacogenetics during pregnancy and lactation

Abstract

Depression occurs during pregnancy in 3.9–12.8% of the women. The different serotonin reuptake inhibitors (SRIs) are metabolized in the liver by CYP450 enzymes. CYP2D6 metabolizes paroxetine, fluoxetine, duloxetine and venlafaxine, while CYP2C19 deactivates citalopram and escitalopram. Polymorphisms in these enzymes change the metabolic clearance and levels of these drugs. Higher metabolism of most SRIs in late pregnancy results in lower maternal levels, which could result in decreased efficacy. Very few studies have addressed the potential interaction between pregnancy-induced increase in 2D6 metabolism and specific genotypes of the women, suggesting that ultra-rapid and extensive metabolizers exhibit lower serum concentrations than the other slower genotypes. Preliminary studies suggest that some genotypes of the serotonin transporter (SLC6A4) promoter are associated and are linked to adverse effects in infants with SRI exposure during pregnancy. Presently, there are no clear clinical implications of SRI pharmacogenetic status in pregnancy and lactation. In late pregnancy, women may exhibit lower steady state concentrations of these drugs, necessitating increased doses but these are presently guided clinically and not through genotyping. Much more work is needed to define whether SRI genotype has clinical implications and predictive value for either mother or offspring.