Antidepressants in breast milk; comparative analysis of excretion ratios

Abstract

Despite increasing prescription rates of antidepressants in pregnant and breastfeeding women over the past decades, evidence of drug exposure for neonates through lactation is very sparse. Concentrations of three antidepressants citalopram, sertraline, and venlafaxine were measured in maternal blood and breast milk in 17 women receiving antidepressant therapy during breastfeeding period. We also computed concentration-by-dose-ratios (C/D) and milk to serum (plasma) penetration ratios (M/P). Non-parametric tests were applied. Serum concentration of citalopram and daily dosage correlated positively while daily dosage and mother milk concentration did not (rho = 0.939, p = 0.005, and rho = 0.772, p > 0.05 respectively). A significant correlation was also found between serum and milk concentrations (rho = 0.812, p = 0.05). Venlafaxine daily dosage correlated positively with the active moiety milk concentration (rho = 0.949, p = 0.014). No significant correlations were reported for sertraline. The amount of antidepressant concentrations to which neonates may be exposed, assessed as absolute infant dose (AID), was particularly low with the highest median AID being 0.16 mg/kg/day for venlafaxine. No significant difference was detected for the M/P ratios between different drugs (p > 0.05), whereas the comparison of C/D ratios revealed lower values in the sertraline group, with the highest values reported for citalopram group (p = 0.007 for serum concentrations and p = 0.008 for mother milk). Findings suggest that breastfeeding under antidepressant treatment constantly exposes children with measurable drug concentrations. As daily dosage and serum concentration of the antidepressants did not predict drug concentrations in mother milk, measuring of drug concentrations in milk helps to quantify drug exposure during breastfeeding. More data-even data of drug concentrations in breastfed children-are needed to better assess the effects of drug exposure on children's development.

Real-world pharmacological treatment of patients with postpartum depression in China from 2016 to 2020: A cross-sectional analysis

“…It was discovered in a study of a population pharmacokinetic model of escitalopram and its main metabolites in patients with perinatal depression that the daily dose of escitalopram via breast milk in breastfed infants was 3.3% of the weight-adjusted dose in pregnant women ( Weisskopf et al, 2016 ). Escitalopram and sertraline are the safest SSRIs for pregnant women, and paroxetine and sertraline are the first choices for breastfeeding women ( Langan and Goodbred, 2016 , Schoretsanitis et al, 2019 , Orsolini and Bellantuono, 2015 ). Paroxetine is almost undetectable in the blood of breastfed infants, and its breast milk concentration/maternal plasma concentration is 5% ( Oberlander et al, 2005 ).…”

Effect of Parenting Interventions on Perinatal Depression and Implications for Infant Developmental Outcomes: A Systematic Review and Meta-Analysis

“…A systematic review by Suri and colleagues (Suri, Lin, Cohen, & Altshuler, 2014) found that the use of selective serotonin reuptake inhibitors (SSRI) in pregnancy could disrupt the child's motor and language development. Controversies around the use of antidepressants during the perinatal period (Ornoy & Koren, 2014) and evidence suggesting that the presence of antidepressants in breast milk could impact infants' development (Schoretsanitis et al, 2019;Wisner, Perel, & Findling, 1997) may partly explain why depressed mothers are reluctant to seek pharmacological treatment. However, as discussed by Casper (2015), the risks of antidepressant use in pregnancy are relatively low and the benefits frequently outweigh the risks of untreated depression, which may contribute to reduced antenatal care, poor feeding, suicidal ideation and substance use (Robinson, 2015).…”

Passage of Venlafaxine in Human Milk During 12 Months of Lactation: A Case Report

“…The metabolite-to-parent drug ratio of desmethylvenlafaxine and venlafaxine measured from 1 month to 12 months in breast milk remained stable, with a mean value of 3.4 (SD = 0.22), which is in agreement with ranges reported in the literature. 8 A high passage of venlafaxine was observed in breast milk from birth until 12 months after delivery, with milk concentrations significantly higher than the dose measured in maternal plasma samples. This trend was also confirmed by the relative infant dose value, which exceeded the safe cut-off of 10%, at 2 months after delivery, posing potential safety concerns.…”