Psychotropic medication in pregnancy and lactation and early development of exposed children

Abstract

There is still limited knowledge about alterations of blood concentrations of psychotropic drugs during pregnancy, the transfer of psychotropic drugs into breastmilk and the effects on exposed children. We investigated changes in concentrations of psychopharmacological medication during pregnancy and lactation in serum and breastmilk at different time points in a naturalistic sample of 60 mothers and observed the development of the exposed children in the first 12 months. We found a decrease in serum concentrations from the first to the second trimester of amitriptyline, duloxetine, escitalopram, quetiapine and sertraline. Citalopram stayed rather stable during pregnancy, sertraline levels interestingly increased again from the second to the third trimester. High concentration‐by‐dose ratios in breastmilk were found for venlafaxine as well as lamotrigine, low for quetiapine and clomipramine. Similarly, clomipramine and quetiapine showed low milk/serum–penetration ratios. Regarding the birth outcome measures in children, we found no significant differences between in utero exposed compared to nonexposed newborns. There were no significant differences in the development in the first 12 months. Psychotropic medication in the peripartum needs a balancing of risks and benefits and a continuous therapeutic drug monitoring can be a guidance for clinicians to monitor drug alteration patterns, which are likely to occur due to physiological pregnancy‐associated changes in pharmacokinetics. Accordingly, therapeutic drug monitoring can optimize a medication in pregnancy and lactation with the lowest effective dose.

Pharmacokinetics of Antidepressants in Pregnancy

“…Leutritz et al 42 . also reported a decreased exposure of sertraline in 11 patients during pregnancy.…”

“…Sertraline is metabolized by multiple enzymes, which are altered in different ways during pregnancy (e.g., increased CYP2B6, CYP3A4, and CYP2D6 activity but decreased CYP2C19 activity), 13 making it difficult to predict the overall effect on sertraline concentrations. Four studies reported lower sertraline concentrations in late pregnancy compared to postpartum, though only one study demonstrated statistical significance 42,44–46 . In contrast, one study reported a significant increase in maternal sertraline concentrations during pregnancy and higher concentrations in the third trimester than in nonpregnant individuals 39 .…”

“…Forty publications on 15 antidepressants studied in 961 pregnant women were identified (Tables S1 and S2). Seventeen manuscripts contained PK data for multiple drugs 26–42 . No information was found regarding PK of desvenlafaxine, milnacipran, viloxazine, levomilnacipran, nefazodone, desipramine, doxepin, amoxapine, maprotiline, protriptyline, trimipramine, vilazodone, esketamine, vortioxetine, isocarboxazid, phenelzine, and tranylcypromine in pregnancy.…”

“…In the Leutritz study, eight women were taking escitalopram but only one serum escitalopram concentration was reported in each trimester 42 . The C/D ratio was 1.93, 1.47, and 0.6 in the first, second, and third trimester.…”

“…Venlafaxine maternal serum concentrations were reported in the second and third trimesters and postpartum in the Leutritz study from eight women 42 . The mean C/D ratio was 1.26 in the second trimester ( n = 3) and 0.96 in the third trimester ( n = 3).…”