Sertraline concentrations in pregnant women are steady and the drug transfer to their infants is low

E Heinonen,K Wide,A Pohanka,M Blennow,L L Gustafsson,M Hovstadius,M Blomdahl-Wetterholm,J Nasiell

doi:10.1007/s00228-021-03122-z

Abstract

PurposeSertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants.MethodPregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed.ResultsNine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants.ConclusionPlacental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment.Trial registrationThe trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

Highlights

Sertraline is one of the most commonly used selective serotonin reuptake inhibitors (SSRI) during pregnancy, and generally proven safe for this use [1,2,3,4,5,6]
Designing a randomized controlled trial, we aimed to clarify several aspects of the effects of antidepressant treatment on the pregnant mother and her infant. In this pharmacokinetic part of the study, we aimed to clarify the variability in plasma sertraline concentrations during pregnancy and demonstrate whether therapeutic drug monitoring (TDM) would improve the safety and efficacy of the treatment
Nine women with two or more available sertraline plasma concentrations are included in the analysis (Table 2, Table 3, Supplemental Fig. 2)

Summary

Introduction

Sertraline is one of the most commonly used selective serotonin reuptake inhibitors (SSRI) during pregnancy, and generally proven safe for this use [1,2,3,4,5,6]. Sertraline is over 98% protein bound in plasma, binding to both albumin and alfa 1-acid-glycoprotein (AAP), but most likely mainly to AAP [18,19,20]. The levels of both albumin and AAP decrease during pregnancy, potentially affecting the sertraline plasma concentrations [21]. Multiple Cytochrome P450 (CYP) enzymes in the liver metabolize sertraline to its main weakly active metabolite Ndesmethylsertraline [22]. The activity of these enzymes is genetically coded [23]. As the pharmacokinetics change during pregnancy, therapeutic drug monitoring (TDM) might be a way to improve both safety and efficacy of the treatment [7, 12, 16, 17]

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