The full, clinically endorsed recommendation should be obtained from Lareb [link].   

Clinical Overview  

Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely used for antenatal depression and anxiety disorders because of its tolerability and comparatively reassuring safety profile for the foetus and neonate. Untreated depression significantly affects maternal quality of life and is linked to preterm birth, foetal growth restriction, and postpartum depression. Because pregnancy alters the activity of drug metabolizing enzymes and foetal exposure occurs, dose-adjustments may be necessary to maintain effective concentrations during pregnancy.  

Pharmacokinetics of sertraline in pregnancy 

Sertraline is mainly metabolized by the hepatic enzymes CYP2C19, CYP3A4 and CYP2D6. While the activity of CYP2C19 decreases during pregnancy, the activity of CYP3A4 and CYP2D6 is significantly elevated. The majority of the pharmacokinetic studies show reduced maternal plasma concentrations of sertraline during the second and third trimesters. The extent of reduction in maternal plasma concentration varies widely, most likely explained by genetic variations in this metabolism. Studies show that sertraline crosses the placenta, with foetal concentrations that are approximately 40% of maternal concentrations.   

Efficacy and safety of sertraline in pregnancy 

There is no clinical evidence on how pregnancy alters the dose–response relationship of sertraline. Hormonal changes, particularly rising oestrogen, may influence treatment response in the brain, although the evidence is limited (10,19). Based on clinical experience, the effect of sertraline varies significantly between patients. Sertraline is generally considered one of the preferred pharmacological treatments during pregnancy because of its relatively favourable safety profile. A slightly increased risk of cardiac anomalies after first-trimester exposure cannot be excluded. Furthermore, there is not sufficient evidence to draw conclusions on the risk of miscarriage, preterm birth and low birth weight. Research on the effects of higher doses is scarce, though one study suggests that maternal doses above 100 mg in the third trimester may increase the risk of poor neonatal adaptation syndrome. 

Conclusion  

Taken together, the pharmacokinetic information indicates reduced maternal plasma concentration of sertraline during the second and third trimester. However, the extension of reduction varies widely across individuals during pregnancy. Therefore, some women may need dose-adjustments in the second or third trimesters, depending on observed clinical response. The benefits for both mother and foetus of adequately treated antenatal depression have to be weighed against the potential risks for the foetus of (higher) sertraline dosing.