Antidepressant transfer into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis

Prog Neuropsychopharmacol Biol Psychiatry. 2021 Apr 20:107:110228. doi: 10.1016/j.pnpbp.2020.110228. Epub 2021 Jan 2.


Objective: Data regarding the ability of antidepressants to enter fetal, newborn and infant fluids have become gradually available, but mechanisms of antidepressant transfer remain poorly understood. Here we calculated penetration ratios in an array of matrices from combined samples of pregnant/breastfeeding women taking antidepressants.

Method: We performed a systematic literature search of PubMed and EMBASE to identify studies with concentrations of antidepressants from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal plasma concentration. When data from multiple studies were available, we calculated combined penetration ratios, weighting the study mean by study size.

Results: Eighty-five eligible studies were identified. For amniotic fluid, the highest penetration ratios were estimated for venlafaxine (mean 2.77, range 0.43-4.70 for the active moiety) and citalopram (mean 2.03, range 0.35-6.97), while the lowest ratios were for fluvoxamine (mean 0.10) and fluoxetine (mean 0.11, range 0.02-0.20 for the active moiety). For umbilical cord plasma, nortriptyline had the highest ratio (mean 2.97, range 0.25-26.43) followed by bupropion (mean 1.14, range 0.3-5.08). For breast milk, the highest ratios were observed for venlafaxine (mean 2.59, range 0.85-4.85), mianserin (mean 2.22, range 0.80-3.64) and escitalopram (mean 2.19, range 1.68-3.00).

Conclusion: We observed considerable variability across antidepressants regarding their ability to enter fetal, newborn and infant fluids. Measuring antidepressant concentrations in a maternal blood sample can provide a reliable estimate of fetal/infant exposure, although further evidence for concentration-dependent effects is required.

Keywords: Amniotic fluid; Antidepressants; Breast milk; Lactation; Pregnancy.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Amniotic Fluid / drug effects
  • Amniotic Fluid / metabolism*
  • Antidepressive Agents / metabolism*
  • Antidepressive Agents / therapeutic use
  • Breast Feeding
  • Female
  • Fetal Blood / drug effects
  • Fetal Blood / metabolism*
  • Humans
  • Infant
  • Milk, Human / drug effects
  • Milk, Human / metabolism*
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Complications / metabolism


  • Antidepressive Agents