Abstract
Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy and the postpartum period. These drugs are capable of crossing the placenta and being transferred to the newborn during lactation. This report reviews the available information regarding the effects of SSRIs on the fetus and newborn; including long-term neurodevelopmental outcomes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Burke KC, Burke Jr JD, Rae DS, Regier DA . Comparing age at onset of major depression and other psychiatric disorders by birth cohorts in five US community populations. Arch Gen Psychiatry 1991;48:789–795.
Kessler RC, McGonagle KA, Zhao S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19.
Wisner KL, Perel JM . Psychopharmacological treatment during pregnancy and lactation. In: Jensvold MF, Halbreich U, Hamilton JA, editors. Psychopharmacology and Women: Sex, Gender and Hormones. Washington DC: American Psychiatric Press; 1996. pp. 191–224.
Field T . Infants of depressed mothers. Infant Behav Dev 1995;18:1–13.
Marcus SM, Flynn HA, Blow FC, KL . Depressive symptoms among pregnant women screened in obstetrics settings. J Womens Health (Larchmt) 2003;12:373–380.
Lundy B, Jones N, Field T, et al. Prenatal depression effects on neonates. Infant Behav Dev 1999;22:119–129.
Preti A, Cardascia L, Tiziana Z, et al. Obstetric complications in patients with depression—a population-based case-control study. J Affective Disord 2000;61:101–106.
Dayan J, Creveuil C, Herlicoviez M, et al. Role of anxiety and depression in the onset of spontaneous preterm labor. Am J Epidemiol 2002;155:293–301.
Orr ST, James SA, Blackmore-Prince C . Maternal prenatal depressive symptoms and spontaneous preterm births among African-American women in Baltimore, Maryland. Am J Epidemiol 2002;156:797–802.
Hoffman S, Hatch M . Depressive symptomatology during pregnancy: evidence for an association with decreased fetal growth in pregnancies of lower social class women. Health Psychol 2000;19:535–543.
Kurki T, Hiilesmaa V, Raitasalo R, Mattila H, Ylikorkala O . Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet Gynecol 2000;95:487–490.
Vaswani M, Linda FK, Ramesh S . Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:85–102.
Whitaker-Azmitia PM, Druse M, Walker P, Lauder JM . Serotonin as a developmental signal. Behav Brain Res 1996;73:19–29.
Pohland RC, Byrd TK, Hamilton M, Koons JR . Placental transfer and fetal distribution of fluoxetine in the rat. Toxicol Appl Pharmacol 1989;98:198–205.
Costa LG, Steardo L, Cuomo V . Structural effects and neurofunctional sequelae of developmental exposure to psychotherapeutic drugs: experimental and clinical aspects. Pharmacol Rev 2004;56:103–147.
Cabrera-Vera TM, Battaglia G . Prenatal exposure to fluoxetine (Prozac) produces site-specific and age-dependent alterations in brain serotonin transporters in rat progeny: evidence from autoradiographic studies. J Pharmacol Exp Ther 1998;286:1474–1481.
Hansson SR, Mezey E, Hoffman BJ . Serotonin transporter messenger RNA expression in neural crest-derived structures and sensory pathways of the developing rat embryo. Neuroscience 1999;89:243–265.
Anderson GM . Peripheral and central neurochemical effects of the selective serotonin reuptake inhibitors (SSRIs) in humans and nonhuman primates: assessing bioeffect and mechanisms of action. Int J Dev Neurosci 2004;22:397–404.
Addis A, Koren G . Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies. Psychol Med 2000;30:89–94.
Chambers CD, Johnson KA, Dick LM, Felix RJ, Jones KL . Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 1996;335:1010–1015.
Heikkinen T, Ekblad U, Laine K . Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placenta. Br J Obstet Gynecol 2002;109:1003–1008.
Hendrick V, Stowe ZN, Altshuler LL, et al. Placental passage of antidepressant medications. Am J Psychiatry 2003;160:993–996.
Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K . Citalopram in pregnancy and lactation. Clin Pharmacol Ther 2002;72:184–191.
Isbister GK, Dawson A, Whyte IM, et al. Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch Dis Child Fetal Neonatal Ed 2001;85:F147–F148.
Haddad PM . Antidepressant discontinuation syndromes. Drug Saf 2001;24:183–197.
Sternbach H . The serotonin syndrome. Am J Psychiatry 1991;148:705–713.
Oberlander TF, Misri S, Fitzgerald CE, et al. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004;65:230–237.
Kallen B . Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004;158:312–316.
Simon GE, Cunningham ML, Davis RL . Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002;159:2055–2061.
Ericson A, Kallen B, Wiholm B . Delivery outcome after the use of antidepressants in early pregnancy. Eur J Clin Pharmacol 1999;55:503–508.
Suri R, Altshuler L, Hendrick V, et al. The impact of depression and fluoxetine treatment on obstetrical outcome. Arch Women's Mental Health 2004;7:193–200.
Zeskind PS, Stephens LE . Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004;113:368–375.
Hendrick V, Smith LM, Suri R, et al. Birth outcomes after prenatal exposure to antidepressant medication. Am J Obstet Gynecol 2003;188:812–815.
Nulman I, Rovet J, Stewart DE, et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002;159:1889–1895.
Kulin NA, Pastuszak A, Sage SR, et al. Pregnancy outcome following maternal use of the new selective serotonin reuptake inhibitors: a prospective controlled multicenter study. JAMA 1998;279:609–610.
Nulman I, Rovet J, Stewart DE, et al. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258–262.
Pastuszak A, Schick-Boschetto B, Zuber C, et al. Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). JAMA 1993;269:2246–2248.
Zeskind PS, Stephens LE . Maternal selective serotonin reuptake inhibitor use during pregnancy and newborn neurobehavior. Pediatrics 2004;113:368–375.
Costei AM, Kozer E, Ho T, Ito S, Koren G . Perinatal outcome following third trimester exposure to paroxetine. [See comment]. Arch Pediatr Adolesc Med 2002;156:1129–1132.
Goldstein DJ . Effects of third trimester fluoxetine exposure on the newborn. J Clin Psychopharmacol 1995;15:417–420.
Costei AM, Kozer E, Ho T, Ito S, Koren G . Perinatal outcome following third trimester exposure to paroxetine. Arch Pediatr Adolesc Med 2002;156:1129–1132.
Cohen LS, Heller VL, Bailey JW, et al. Birth outcomes following prenatal exposure to fluoxetine. Biol Psychiatr 2000;48:996–1000.
Casper RC, Fleisher BE, Lee-Ancajas JC, et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003;142:402–408.
Hendrick V, Smith LM, Suri R, et al. Birth outcomes after prenatal exposure to antidepressant medication. Am J Obstet Gynecol 2003;188:812–815.
Chambers C, Dick LM, Felix RJ, Johnson KA, Jones KL . Pregnancy Outcome in women who use sertraline. Teratology 1999;59:376.
Goldstein DJ, Corbin LA, Sundell KL . Effects of first-trimester fluoxetine exposure on the newborn. Obstet Gynecol 1997;89:713–718.
Pastuszak A, Schick-Boschetto B, Zuber C, et al. Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). JAMA 1993;269:2246–2248.
Einarson A, Fatoye B, Sarkar M, et al. Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 2001;158:1728–1730.
Laine K, Heikkinen T, Ekblad U, Kero P . Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003;60:720–726.
Aranda J, Edwards D, Hales B, Rieder M . Developmental pharmacology. In: Fanaroff AA, Martin RJ, editors. Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 7th ed. St. Louis: Mosby; 2002. p. 145.
Weissman AM, Levy BT, Hartz AJ, et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161:1066–1078.
Berle JO, Steen VM, Aamo TO, et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome p450 genotypes. J Clin Psychiatry 2004;65:1228–1234.
Hendrick V, Stowe ZN, Altshuler LL, et al. Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk. Biol Psychiatry 2001;50:775–782.
Stowe ZN, Hostetter AL, Owens MJ, et al. The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. J Clin Psychiatry 2003;64:73–80.
Heikkinen T, Ekblad U, Palo P, Laine K . Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation. Clin Pharmacol Ther 2003;73:330–337.
Chambers CD, Anderson PO, Thomas RG, et al. Weight gain in infants breastfed by mothers who take fluoxetine. Pediatrics 1999;104:e61.
Oberlander TF, Eckstein Grunau R, et al. Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr Res 2002;51:443–453.
Morag I, Batash D, Keidar R, et al. Paroxetine use throughout pregnancy: does it pose any risk to the neonate? J Toxicol Clin Toxicol 2004;42:97–100.
Zeskind PS, Oberlander TF, Grunau RE, et al. Continuing effects of prenatal SSRI exposure detected by spectral analysis of infant cry sounds at two months of age. Pediatr Res 2005;57:1624A.
Acknowledgements
This research was supported by the National Institute of Mental Health, MH065062 to DMV, CRN and NK; and MH068489 to DMV and CRN. We thank Robert Schumacher, MD for his helpful comments during the preparation of this manuscript.
Author information
Authors and Affiliations
Additional information
Charles R. Neal, Jr., MD, PhD is presently at the University of Hawaii John A. Burns School of Medicine.
Rights and permissions
About this article
Cite this article
Lattimore, K., Donn, S., Kaciroti, N. et al. Selective Serotonin Reuptake Inhibitor (SSRI) Use during Pregnancy and Effects on the Fetus and Newborn: A Meta-Analysis. J Perinatol 25, 595–604 (2005). https://doi.org/10.1038/sj.jp.7211352
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jp.7211352
This article is cited by
-
Descriptive analysis of adverse drug reaction reports in children and adolescents from Germany: frequently reported reactions and suspected drugs
BMC Pharmacology and Toxicology (2021)
-
Identifying Drugs Inducing Prematurity by Mining Claims Data with High-Dimensional Confounder Score Strategies
Drug Safety (2020)
-
Prenatal depression screening and antidepressant prescription: obstetrician-gynecologists’ practices, opinions, and interpretation of evidence
Archives of Women's Mental Health (2018)
-
Could use of Selective Serotonin Reuptake Inhibitors During Lactation Cause Persistent Effects on Maternal Bone?
Journal of Mammary Gland Biology and Neoplasia (2018)
-
Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression: an observational cohort study
Journal of Perinatology (2017)