Breastfeeding During Maternal Antidepressant Treatment With Serotonin Reuptake Inhibitors: Infant Exposure, Clinical Symptoms, and Cytochrome P450 Genotypes

Jan Øystein Berle, M.D.; Vidar M. Steen, M.D., Ph.D.; Trond Oskar Aamo, M.D.; Harald Breilid, M.Sc.; Kolbjørn Zahlsen, M.Sc.; and Olav Spigset, M.D., Ph.D.

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.

Method: 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.

Conclusion: 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 antidepressants.

(J Clin Psychiatry 2004;65:1228-1234)

Received Nov. 19, 2003; accepted April 21, 2004. From the Centre for Child and Adolescent Mental Health (Dr. Berle) and the Dr. Einar Martens Research Group for Biological Psychiatry and Locus on Neuroscience, Center for Medical Genetics and Molecular Medicine (Drs. Steen and Breilid), University of Bergen, Bergen; the Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen (Drs. Steen and Breilid); and the Department of Clinical Pharmacology, St. Olav's University Hospital, Trondheim (Drs. Aamo, Zahlsen, and Spigset), Norway.

In the spirit of full disclosure and in compliance with all ACCME Essential Areas and Policies, the faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Drs. Berle, Steen, Aamo, Breilid, Zahlsen, and Spigset have no significant commercial relationships to disclose relative to their presentations.

Corresponding author and reprints: Jan Øystein Berle, M.D., Centre for Child and Adolescent Mental Health, University of Bergen, P.O. Box 7800, N-5020 Bergen, Norway (e-mail: jan.berle@psyk.uib.no).