The full, clinically endorsed dose recommendation should be obtained from Lareb.

Rationale for drug selection  

Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely used for antenatal depression and anxiety disorders. Because pregnancy alters the activity of drug metabolizing enzymes, dose-adjustments may be necessary to maintain effective concentrations during pregnancy.

Pharmacokinetics of sertraline in pregnancy 

Sertraline is mainly metabolized by hepatic enzymes such as CYP2C19, CYP3A4 and CYP2D6. While the activity of CYP2C19 is decreased 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 trimester. The extent of reduction in maternal plasma concentration varies widely, which is likely explained by genetic variations in hepatic enzyme activity. As a result, some pregnant women may benefit from an increased dosage when a reduced effect of sertraline is observed. Studies show that sertraline crosses the placenta, with foetal concentrations that are approximately 40% of maternal concentrations. Maternal–foetal PBPK models were used to asses gestational changes in the maternal plasma concentration of sertraline and explore dosing scenarios for different genetic variations of hepatic enzyme activity. These models provided useful insights for dosing recommendation and supported decision making.

Benefits and risk with proposed dose adjustments 

The expected benefits and associated risk of increasing the dose when reduced effect of sertraline is observed during pregnancy.

In short  

Pregnancy may reduce maternal plasma concentrations of sertraline throughout pregnancy. However, the extension of reduction varies widely across individuals. Possible reduction in sertraline’s effectiveness should be prevented, therefore dose adjustments may be necessary. Based on the weighing of benefits and risks, the working committee derived an appropriate dose adjustment. Consult Lareb for the model-informed dosing recommendations.