The pharmacokinetics of sertraline excretion into human breast milk: Determinants of infant serum concentrations

Abstract

Background: The purpose of this study was to attain a new landmark in the area of selective serotonin reuptake inhibitor therapy during lactation by establishing a basis for interpreting infant serum concentrations and for minimizing infant exposure in the absence of treatment-emergent side effects. Method: Breast milk and paired maternal and infant sera were collected following maternal treatment with sertraline monotherapy (25-200 mg/day) administered once daily. Sertraline and its major metabolite were measured in breast milk and serum samples using high-performance liquid chromatography with UV detection (limit of detection = 2 ng/mL). Results: Twenty-six nursing women with DSM-IV major depressive disorder participated in the study; the mean (SD) daily sertraline dose was 123.9 (62.8) mg/day. Fifteen women submitted 182 breast milk samples for analysis of gradient (foremilk to hindmilk) and time course of medication excretion. The milk/plasma ratio was highly variable (range, 0.42-4.81). A significant gradient and time course of excretion for both sertraline (p < .001 for both) and desmethylsertraline (p < .001 for gradient and p < 2 ng/mL vs. ≥ 2 ng/mL) or absolute concentrations (ng/mL) in infant serum. No adverse events were reported or documented in any infant. Conclusion: These results extend previous studies by demonstrating the utility of breast milk analysis in interpreting infant serum concentrations and minimizing infant exposure.