Risk of Birth Defects With SSRIs Relatively Small

The challenge of achieving consistent results, Byatt says, is partly due to the inability to do randomized comparisons due to ethical concerns, and the difficulty of controlling for maternal illness and severity of illness.

“Pregnancy itself precludes us from using the gold-standard methodology,” Byatt says, “so we’re left with other methodologies, and each have their own pros and cons. This makes it very hard to differentiate whether adverse outcomes are associated with underlying illness, the medication, or other unknown factors associated with either or both.”


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In summarizing their findings regarding malformations, Byatt says in general they found that paroxetine (Paxil) has been the most controversial because it has been associated with an increased risk of overall major malformations. However, it is also important to note that not all studies support this finding.

“SSRIs remain the most studied antidepressants in pregnancy. Malformations are rare, and the absolute risks appear small,” Byatt says. “No single type of malformation has been consistently observed across studies with any commonly used antidepressant.”

Byatt’s team concluded that while some individual studies suggest associations between SSRIs and some specific major malformations, the findings are inconsistently observed and the absolute risks appear small.

With regard to norepinephrine-dopamine reuptake inhibitors (NDRIs) such as bupropion (Wellbutrin), and serotonin-norepinephrine reuptake inhibitors (SNRIs), including duloxetine (Cymbalta), venlafaxine (Effexor XR), and desvenlafaxine (Pristiq), Byatt says that while the limited available data suggest a possible association between bupropion and congenital heart defects, the absolute risk appears low. The limited studies examining SNRIs she says have been reassuring, but further investigation is needed before the risks associated with their use may be fully understood.

The other main area of concern is birth complications. These can include risks of preterm birth, infant-fetal growth, and postnatal syndromes, including PNAS and PPHN. Byatt’s group concluded that while the available evidence is conflicting, the overall data suggests that PNAS can occur in neonates exposed to SSRIs and SNRIs, yet have most often been reported after exposure to paroxetine, fluoxetine, and venlafaxine.

With regard to PPHNs, in 2006, the FDA published a Public Health Advisory regarding an increased risk of PPHN associated with the use of SSRIs after week 20 of pregnancy. However, it was rescinded in 2011 after the agency concluded that there was insufficient evidence that antidepressant exposure during pregnancy causes PPHN. Byatt’s analysis of the literature concurred and concluded that an association between antidepressant use and PPHN is either small, or non-existent.

Autism and ADHD Links to Antidepressant Use Inconsistent

Studies linking autism spectrum disorders (ASD) and ADHD include a pair of studies published this year: Both found inconsistent associations.

A study done at Johns Hopkins University by Harrington and colleagues found that prenatal exposure to SSRIs was nearly three times as likely in boys with ASD relative to those with typical development. They also found developmental delays were higher with prenatal SSRI exposure.

However, they concluded, “Findings from published studies on SSRIs and ASD continue to be inconsistent. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.”4