Antidepressant Studies

New Effexor Study Finds Significant Link to Serious Birth Defects

An epidemiological study of birth defects in the United States has added new evidence to a growing body of data linking antidepressant usage during pregnancy to miscarriage and birth defects, including serious congenital heart defects.

The study was published online on December 26, 2012 in the journal Birth Defects Research, Part A: Clinical and Molecular Teratology. It specifically focused on the effects of the SNRI (serotonin-norepinephrine reuptake inhibitor) antidepressant venlafaxine (Effexor), approved by the U.S. Food and Drug Administration (FDA) to treat depression and anxiety in adults.

A new Effexor study finds significant link to serious birth defects.

Using data from the National Birth Defects Prevention Study, researchers looked at over 19,000 women whose pregnancies (delivery dates between 1997 and 2007) had been affected by one of 30 different birth defects. Another 8,002 women with normal births served as controls. The researchers found “statistically significant associations” between exposure to venlafaxine and the following defects:

Anencephaly – a fatal neural tube defect characterized by an absence of a large part of the brain and skull. It occurs during early development, when the neural tube of an unborn baby fails to close. Babies born with anencephaly usually die within days after their birth.

Atrial septal defects (ASD) – described as a hole in the heart, ASD is a congenital heart defect that allows blood to flow between two chambers of the heart that are normally separated – the left and right atria. The wall of the heart, called the septum, usually separates the atria. In babies with ASD, oxygen –rich blood in one side of the heart directly mixes with the oxygen-poor blood of the other, leading to poor oxygen levels in the blood.

Coarctation of the aorta – a narrowing of the aorta, the large blood vessel that distributes oxygenated blood from the heart to all parts of the body. The narrowing, or coarctation, of the aorta makes it difficult for blood to flow through the artery, resulting in symptoms like chest pain, failure to thrive, poor growth and shortness of breath. Most infants with coarctation of the aorta will need surgery to treat the condition.

Cleft palate – a craniofacial defect characterized by an opening in the roof of the mouth which can range from a small notch to a split that runs along the entire length of the palate. Children with cleft palates may appear deformed, have problems with feeding and speech and may be at risk of developing ear infections. Treatment for cleft palate usually involves surgery within the first year of life.

Gastroschisis – a birth defect in which the baby’s intestines stick out of the body through a hole in the abdominal wall. An infant both with gastroschisis will have unprotected intestines exposed to amniotic fluid in the womb. Babies born with this birth defect will need surgery, and prognosis depends on the size of the abdominal cavity and severity of the birth defect.

In this study exposure to venlafaxine was defined to be any reported use of the drug from one month preconception through the third month of pregnancy. To assess only the effects of venlafaxine, women who reported using other antidepressants were excluded from the study. To control for the possibility that some mothers who reported no exposure had in fact taken the drug, the authors reassessed their data assuming that the actual number of control mothers who had taken venlafaxine was 30% higher than the number who reported exposure. Their reassessment nevertheless found “all associations remained elevated.”

Discussing the implications of their results, the researchers noted that the two neurotransmitters most affected by venlafaxine, serotonin and norepinephrine, have been shown to play an important role in the development of the embryo into a fetus. They wrote, “Thus, if venlafaxine is taken during early pregnancy and interferes with these embryologic signaling pathways, it is plausible that venlafaxine could affect craniofacial and cardiac development. This is consistent with our findings of associations with septal heart defects, LVOTO defects [left ventricular outflow tract obstruction. Coarctation of the aorta is one example of this defect.], and cleft palate.”

The authors concluded, “Our data suggest associations between periconceptional [occurring around the time of conception] use of venlafaxine and some birth defects” and called for additional studies to confirm their results.


Polen KN, Rasmussen SA, Riehle-Colarusso T, Reefhuis J and the National Birth Defects Prevention (2012). Association between Reported Venlafaxine Use in Early Pregnancy and Birth Defects, National Birth Defects Prevention Study, 1997-2007. Birth Defects Research, Part A: Clinical and Molecular Teratology. doi:10.1002/bdra.23096.

Summary Information


Association between reported venlafaxine use in early pregnancy and birth defects, National Birth Defects Prevention Study, 1997-2007


Kara N. D. Polen, Sonja A. Rasmussen, Tiffany Riehle-Colarusso, JennitaReefhuis and the National Birth Defects Prevention Study, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia


Birth Defects Research (Part A) 97:2835 (2013).  Published online 26 December 2012.


This work was supported through cooperative agreements under PA 96043, PA 02081, and FOA DD09-001 from the Centers for Disease Control and Prevention to the Centers for Birth Defects Research and Prevention participating in the National Birth Defects Prevention Study