Academy of Diagnostics & Laboratory Medicine - Scientific Short

Antidepressant use in postpartum depression: to breastfeed or not to breastfeed?

Sarah Delaney

The infant and maternal benefits to breastfeeding are numerous and well established. Because of this, more women are choosing to breastfeed their infants and continuing breastfeeding for longer. However, 10-15% of new mothers are affected by postpartum depression (PPD). Escitalopram (ESC) is an antidepressant drug that is one of the first-line medications to treat this disorder; yet, safety information about ESC use during breastfeeding and the extent of drug exposure to the nursing infant is limited. Current medical guidance suggests that the benefits of using antidepressants to treat PPD outweigh the risks, as children of depressed mothers have poor cognitive and behavioral outcomes. This highlights the need to better understand how much ESC may enter the breast milk and how much may reach the infant plasma.

By establishing an approach to monitor milk and infant plasma drug levels, we will generate much-needed safety data, which will safeguard the infant from potential drug exposure and allow women to confidently breastfeed while using their medication.

To determine how much ESC is excreted into breast milk, we collected 104 steady-state milk samples from 18 lactating women taking ESC, which were then measured with an LC-MS/MS method specifically developed and validated to measure ESC in milk. Breast milk is a dynamic matrix that changes composition throughout the day and even during one feed, transitioning from foremilk to hindmilk. Therefore, theoretically, drug concentrations can vary during feeding depending on the physicochemical properties of the drug, highlighting the importance of sampling phase on drug monitoring and infant exposure estimates. In order to determine whether ESC accumulates in the foremilk or hindmilk, we collected 17 paired foremilk and hindmilk samples from a series of time points across the dosing interval. While there was a significantly higher concentration of ESC in the hindmilk, the mean difference in concentration between the two phases was less than 10%. This suggests that milk phase has a negligible impact on infant exposure and that either foremilk or hindmilk could be used to monitor drug levels.

To define the dose of ESC an infant would be exposed to through breastfeeding, we generated an infant’s daily dose (in mg/kg/day) using the measured ESC milk concentrations from our study along with feeding parameters from the literature (e.g. volume of milk consumed and frequency of feeds). Based on our measured milk concentrations, breastfeeding infants were exposed to a dose of ESC approximately 2.6% of the maternal weight-normalized dose, which is well below the accepted limit of 10% (1). This suggests that infants would be exposed to low levels of ESC through nursing. To simulate the infant ESC plasma concentrations following ESC exposure through breastfeeding, we generated an infant physiologically-based pharmacokinetic model. This model was developed using age-specific physiological and anatomical factors that could influence infant pharmacokinetic parameters. The steady-state plasma exposure in our “virtual” infant model was 1.7% of the mean maternal plasma concentration. This further supports that total ESC exposure is relatively low and could be compatible with breastfeeding.

This study served as a proof-of-principle approach that translated drug monitoring data of ESC in breast milk into infant plasma concentration predictions, eliminating the need for invasive infant blood sampling. Taking advantage of simulation and modeling approaches provided a powerful tool to better understand drug exposure and safety during lactation.

 

(1) Bennett PN. Use of the monograph on drugs. In: Bennett PN. Drugs and Human Lactation. 2nd ed. Amsterdam, Netherlands: Elsevier; 1996:67–74

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Academy of Diagnostics & Laboratory Medicine Designation

Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.