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Review ArticleReview Article

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

Chase H. Bourke, Zachary N. Stowe and Michael J. Owens
David R. Sibley, ASSOCIATE EDITOR
Pharmacological Reviews April 2014, 66 (2) 435-465; DOI: https://doi.org/10.1124/pr.111.005207
Chase H. Bourke
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia (C.H.B., M.J.O.); and Department of Psychiatry, Pediatrics and Gynecology and Obstetrics, University of Arkansas Medical Sciences Center, Little Rock, Arkansas (Z.N.S.)
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Zachary N. Stowe
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia (C.H.B., M.J.O.); and Department of Psychiatry, Pediatrics and Gynecology and Obstetrics, University of Arkansas Medical Sciences Center, Little Rock, Arkansas (Z.N.S.)
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Michael J. Owens
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia (C.H.B., M.J.O.); and Department of Psychiatry, Pediatrics and Gynecology and Obstetrics, University of Arkansas Medical Sciences Center, Little Rock, Arkansas (Z.N.S.)
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David R. Sibley
Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia (C.H.B., M.J.O.); and Department of Psychiatry, Pediatrics and Gynecology and Obstetrics, University of Arkansas Medical Sciences Center, Little Rock, Arkansas (Z.N.S.)
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Abstract

Pharmacological treatment of any maternal illness during pregnancy warrants consideration of the consequences of the illness and/or medication for both the mother and unborn child. In the case of major depressive disorder, which affects up to 10–20% of pregnant women, the deleterious effects of untreated depression on the offspring can be profound and long lasting. Progress has been made in our understanding of the mechanism(s) of action of antidepressants, fetal exposure to these medications, and serotonin’s role in development. New technologies and careful study designs have enabled the accurate sampling of maternal serum, breast milk, umbilical cord serum, and infant serum psychotropic medication concentrations to characterize the magnitude of placental transfer and exposure through human breast milk. Despite this progress, the extant clinical literature is largely composed of case series, population-based patient registry data that are reliant on nonobjective means and retrospective recall to determine both medication and maternal depression exposure, and limited inclusion of suitable control groups for maternal depression. Conclusions drawn from such studies often fail to incorporate embryology/neurotransmitter ontogeny, appropriate gestational windows, or a critical discussion of statistically versus clinically significant. Similarly, preclinical studies have predominantly relied on dosing models, leading to exposures that may not be clinically relevant. The elucidation of a defined teratological effect or mechanism, if any, has yet to be conclusively demonstrated. The extant literature indicates that, in many cases, the benefits of antidepressant use during pregnancy for a depressed pregnant woman may outweigh potential risks.

Footnotes

  • This work was supported by the National Institutes of Health National Institute of Mental Health [Grant MH077928] (to C.H.B. and M.J.O.); and the National Institutes of Health National Institute of Environmental Health Sciences [Grant ES012870] (to C.H.B.). Financial disclosure (preceding 12 months or anticipated in next 12 months) are indicated as follows: C.H.B. has no conflicts of interest or financial disclosures; M.J.O. received research grants from the National Institutes of Health, Lundbeck A/S, Cyberonics, Dainippon Sumitomo Pharma, SK Life Sciences, Sunovion Pharmaceuticals; serves as a consultant to H. Lundbeck A/S, R.J. Reynolds, and the United States Department of Justice; and receives compensation for these services (the terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies); and holds a patent [Owens MJ and Nemeroff CB (2004) Method of assessing antidepressant drug therapy via transport inhibition of monoamine neurotransmitters. U.S. Patent 7,148,027 B2, 12 Dec 2006.]; Z.N.S. received research support from the National Institutes of Health, GlaxoSmithKline, Pfizer, and Wyeth; served on speakers and/or advisory boards for Pfizer, Eli Lilly, Wyeth, BristolMyers-Squibb, and GlaxoSmithKline; and received honoraria from Eli Lilly, GlaxoSmithKline, Pfizer, and Wyeth.

  • Address correspondence to: Dr. Michael J. Owens, Laboratory of Neuropsychopharmacology, Department of Psychiatry and Behavioral Sciences, 101 Woodruff Circle, Suite 4000, Emory University, Atlanta, GA 30322. E-mail: mowens{at}emory.edu

  • dx.doi.org/10.1124/pr.111.005207

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 66 (2)
Pharmacological Reviews
Vol. 66, Issue 2
1 Apr 2014
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Review ArticleReview Article

Prenatal Antidepressant Exposure

Chase H. Bourke, Zachary N. Stowe and Michael J. Owens
Pharmacological Reviews April 1, 2014, 66 (2) 435-465; DOI: https://doi.org/10.1124/pr.111.005207

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Review ArticleReview Article

Prenatal Antidepressant Exposure

Chase H. Bourke, Zachary N. Stowe and Michael J. Owens
Pharmacological Reviews April 1, 2014, 66 (2) 435-465; DOI: https://doi.org/10.1124/pr.111.005207
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