Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes.
BACKGROUND
The aims of the study were to quantify the drug exposure in breastfed infants of antidepressant-treated mothers, to identify possible adverse events, and to correlate these variables to maternal and infant drug metabolism-relevant genotypes and milk triglyceride content.


METHODS
The study included 25 lactating women treated with citalopram (N = 9), sertraline (N = 6), paroxetine (N = 6), fluoxetine (N = 1), or venlafaxine (N = 3) and their 26 breastfed infants. Drug concentrations in maternal and infant serum and milk were analyzed using liquid chromotography mass spectrometry methods; milk triglyceride levels were measured with a commercial kit. Cytochrome P450 (CYP) 2D6 and CYP2C19 activity was determined by polymerase chain reaction-based genotyping of the mothers and infants. An infant adverse event questionnaire was completed by the medication-treated mothers as well as by a control group of medication-free breastfeeding mothers of 68 infants.


RESULTS
Sertraline and paroxetine were not detected in any of the drug-exposed infants. The infant serum level of citalopram was either undetectable (N = 4) or low (N = 6). All venlafaxine-exposed infants had measurable drug concentrations. We identified a paroxetine-treated mother and her infant who were both CYP2D6 poor metabolizers, as well as a citalopram-treated mother with CYP2C19 poor metabolizer status, but the serum drug levels of their infants were still either undetectable (paroxetine) or low (citalopram). There was no evidence of adverse events in the drug-exposed infants.


CONCLUSIONS
Serum drug levels in breastfed infants of antidepressant-treated mothers were undetectable or low. This study adds further evidence to previously published data indicating that breastfeeding should not be generally discouraged in women using serotonin reuptake inhibitor anti-depressants.
Berle
Jan Øystein
JØ
Centre for Child and Adolescent Mental Health, University of Bergen, Bergen, Norway. jean.berle@psyk.uib.no
Steen
Vidar M
VM
Aamo
Trond Oskar
TO
Breilid
Harald
H
Zahlsen
Kolbjørn
K
Spigset
Olav
O
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001942:Breast Feeding; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D019052:Depression, Postpartum / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007774:Lactation / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008895:Milk, Human / Q000737:chemistry* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D017374:Paroxetine / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D010597:Pharmacogenetics; D010641:Phenotype; D011247:Pregnancy; D017367:Selective Serotonin Reuptake Inhibitors / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use*; D020280:Sertraline / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D014280:Triglycerides / Q000032:analysis* / Q000378:metabolism
D001189:Aryl Hydrocarbon Hydroxylases; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014280:Triglycerides; C045793:CYP2C19 protein, human