Correspondence
Sertraline and Breast-Feeding
N Engl J Med 1997; 336:1189-1190April 17, 1997
- Article
To the Editor:
Postpartum depression occurs in approximately 10 percent of women who give birth and is associated with substantial morbidity in mothers and their children. For some women, treatment with an antidepressant drug may be necessary but complicated by their desire to continue to breast-feed. Unfortunately, there is a dearth of information on the safety of treatment with various antidepressant drugs, including the selective serotonin-reuptake inhibitors, during breast-feeding. During gestation, serotonin (5-hydroxytryptamine) influences neurogenesis and morphogenesis, and in the neonatal period it modulates synaptogenesis.1 The effects of 5-hydroxytryptamine on early neurodevelopment arouse special concern about the use of selective serotonin-reuptake inhibitors by nursing mothers. Although plasma drug levels in infants exposed to serotonin-reuptake inhibitors in breast milk are reported to be generally quite low,2 it is not known whether 5-hydroxytryptamine transport in infants is affected.
In humans, platelet and neuronal 5-hydroxytryptamine transporters are identical,3 and studies in animals indicate that reuptake inhibitors cause similar central and peripheral blockade. We measured 5-hydroxytryptamine levels in whole blood from four mothers and their nursing infants before and during treatment with sertraline for postpartum depression. Because of the extremely low levels of plasma free 5-hydroxytryptamine, whole-blood levels are equivalent to platelet levels.4 Since platelet 5-hydroxytryptamine is exogenously derived, these values should reflect the relative extent of the inhibition of 5-hydroxytryptamine transport in mother and infant.
Whole-blood 5-hydroxytryptamine levels in the mothers and their infants were determined before and after treatment of the mothers with sertraline for 9 weeks at a maximal dose of 100 mg per day (mothers of Infants 1 and 3) or 12 weeks at a maximal dose of 50 mg per day (mothers of Infants 2 and 4).4 Plasma sertraline levels were measured at the time of postexposure sampling. Two infants (Infants 1 and 2) were fully breast-fed, whereas the other two infants were breast-fed three or four times daily. At the start of the study, Infant 1 was 15 days old; Infant 2, 26 days; Infant 3, 12 months; and Infant 4, 6 months.
As expected,5 marked declines in platelet 5-hydroxytryptamine levels (to 10.2±2.9 percent of the base-line value) were observed in the mothers after treatment with sertraline. In contrast, little or no change was seen in the levels in the infants exposed to sertraline through breast milk (Figure 1Figure 1
Effect of Sertraline on Platelet 5-Hydroxytryptamine Levels in Four Breast-Fed Infants and Their Mothers.). The data indicate that platelet 5-hydroxytryptamine levels and, hence, transport were not reduced in the infants. Although knowledge of the relation between platelet and neuronal blockade is incomplete, the results also suggest that little central reuptake inhibition occurred. This tentative conclusion is consistent with the low plasma concentrations of sertraline in the nursing infants.Although the possible reuptake-inhibiting effects of sertraline can be assessed on the basis of platelet 5-hydroxytryptamine measurements, it is difficult to completely rule out other, nonspecific pharmacologic effects such as direct receptor stimulation or enzyme activation. The situation is particularly complex because of possible developmental differences in receptor affinities and expression. Thus, conclusions about the safety of sertraline treatment during breast-feeding will always depend somewhat on the assumption that the drug's principal site of action is the 5-hydroxytryptamine transporter. Our data are reassuring, but larger studies are needed to determine conclusively whether mothers receiving sertraline or other selective serotonin-reuptake inhibitors can breast-feed without exposing their infants to physiologically meaningful doses of the drugs.
5 ReferencesC. Neill Epperson, M.D.
George M. Anderson, M.D.
Christopher J. McDougle, M.D.
Yale University School of Medicine, New Haven, CT 065191
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- Citing Articles (21)
Citing Articles
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Laura E. Sockol, C. Neill Epperson, Jacques P. Barber. (2011) A meta-analysis of treatments for perinatal depression. Clinical Psychology Review 31:5, 839-849
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(2008) ABM Clinical Protocol #18: Use of Antidepressants in Nursing Mothers. Breastfeeding Medicine 3:1, 44-52
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Sefi Kronenberg, Alan Apter, David Brent, Shella Schirman, Nadine Melhem, Nimrod Pick, Doron Gothelf, Miri Carmel, Amos Frisch, Abraham Weizman. (2007) Serotonin Transporter Polymorphism (5-HTTLPR) and Citalopram Effectiveness and Side Effects in Children with Depression and/or Anxiety Disorders. Journal of Child and Adolescent Psychopharmacology 17:6, 741-750
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Salvatore Gentile. (2007) Use of Contemporary Antidepressants during Breastfeeding. Drug Safety 30:2, 107-121
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Malin Eberhard-Gran, Anne Eskild, Stein Opjordsmoen. (2006) Use of Psychotropic Medications in Treating Mood Disorders during Lactation. CNS Drugs 20:3, 187-198
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Cheston M. Berlin, Gerald G. Briggs. (2005) Drugs and chemicals in human milk. Seminars in Fetal and Neonatal Medicine 10:2, 149-159
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P??r Hallberg, Viktoria Sj??blom. (2005) The Use of Selective Serotonin Reuptake Inhibitors During Pregnancy and Breast-feeding. Journal of Clinical Psychopharmacology 25:1, 59-73
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GEORGE M. ANDERSON, KATHRYN CZARKOWSKI, NORMAN RAVSKI, C. NEILL EPPERSON. (2004) Platelet Serotonin in Newborns and Infants: Ontogeny, Heritability, and Effect of In Utero Exposure to Selective Serotonin Reuptake Inhibitors. Pediatric Research 56:3, 418-422
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George M. Anderson. (2004) Peripheral and central neurochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in humans and nonhuman primates: assessing bioeffect and mechanisms of action. International Journal of Developmental Neuroscience 22:5-6, 397-404
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CPT Emily C. Clay, MAJ Dean A. Seehusen. (2004) A Review of Postpartum Depression for the Primary Care Physician. Southern Medical Journal 97:2, 157-161
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S Agatonovic-Kustrin, L.H Ling, S.Y Tham, R.G Alany. (2002) Molecular descriptors that influence the amount of drugs transfer into human breast milk. Journal of Pharmaceutical and Biomedical Analysis 29:1-2, 103-119
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C. Lindsay DeVane, Heidi L. Liston, John S. Markowitz. (2002) Clinical Pharmacokinetics of Sertraline. Clinical Pharmacokinetics 41:15, 1247-1266
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Shaila Misri, Xanthoula Kostaras. (2002) Benefits and Risks to Mother and Infant of Drug Treatment for Postnatal Depression. Drug Safety 25:13, 903-911
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Victoria Hendrick, Zachary N. Stowe, Lori L. Altshuler, Jim Mintz, Sun Hwang, Amy Hostetter, Rita Suri, Kristin Leight, Alan Fukuchi. (2001) Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk. Biological Psychiatry 50:10, 775-782
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D. Jeffrey Newport, Molly M. Wilcox, Zachary N. Stowe. (2001) Antidepressants during pregnancy and lactation: Defining exposure and treatment issues. Seminars in Perinatology 25:3, 177-190
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Glenda MacQueen, Leslie Born, Meir Steiner. (2001) The Selective Serotonin Reuptake Inhibitor Sertraline: Its Profile and Use in Psychiatric Disorders. CNS Drug Reviews 7:1, 1-24
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Victoria Hendrick, Zachary N. Stowe, Lori L. Altshuler, Amy Hostetter, Alan Fukuchi. (2000) Paroxetine Use During Breast-Feeding. Journal of Clinical Psychopharmacology 20:5, 587-589
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Lesley M. Arnold, R. F. Suckow, Philip K. Lichtenstein. (2000) Fluvoxamine Concentrations in Breast Milk and in Maternal and Infant Sera. Journal of Clinical Psychopharmacology 20:4, 491-493
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Full Text20
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CrossRef21
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