Changes in Sertraline Plasma Concentrations Across Pregnancy and Postpartum

Area of Science:

• Pharmacology
• Obstetrics
• Genetics

Background:

• Major depressive disorder (MDD) is prevalent during pregnancy.
• Sertraline is a common antidepressant choice for pregnant individuals, but its pharmacokinetics in pregnancy are not well understood.
• Understanding sertraline pharmacokinetics and pharmacogenetics is crucial for optimizing treatment during pregnancy.

Purpose of the Study:

• To characterize plasma sertraline concentration to dose (C/D) ratios throughout pregnancy and postpartum.
• To investigate the impact of pharmacogenetic variability on sertraline elimination during pregnancy.
• To identify potential risks for subtherapeutic sertraline concentrations in pregnant individuals.

Main Methods:

• Prospective observational cohort study of 47 pregnant individuals with MDD on maintenance sertraline therapy.
• Blood samples collected every 4 weeks during pregnancy and twice postpartum for sertraline and desmethylsertraline concentration measurements.
• Analysis of sertraline C/D ratios and sertraline/desmethylsertraline ratios, considering CYP2C19 genotype.

Main Results:

• Mean sertraline C/D ratios were consistently lower during pregnancy compared to postpartum (22% lower in the last 4 weeks of pregnancy).
• Increased sertraline elimination during pregnancy was indicated by higher sertraline/desmethylsertraline ratios after birth.
• Individuals with poor or intermediate CYP2C19 activity showed a 51% decrease in sertraline C/D ratios during pregnancy.

Conclusions:

• Sertraline C/D ratios decrease significantly during pregnancy, particularly in individuals with reduced CYP2C19 activity.
• Pregnant individuals with poor or intermediate CYP2C19 activity may be at risk for subtherapeutic sertraline levels.
• These findings highlight the importance of therapeutic drug monitoring and potential dose adjustments for sertraline in pregnant populations, especially considering genetic factors.