Associations could help inform risk-benefit of antidepressant use during pregnancy

There are some associations between maternal antidepressant use and specific birth defects, researchers found.

However, some of these associations are attenuated when accounting for underlying conditions.

The study, led by Kayla N. Anderson, PhD, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, was published in JAMA Psychiatry.

Depressive and anxiety disorders are common in the United States, affecting about 7% of the adult population. According to the National Institutes of Health, these disorders disproportionately affect reproductive-age women, and furthermore, they are prevalent among pregnant women, with 6% to 8% reporting being prescribed or using an antidepressant.

According to Anderson and colleagues, while studies have shown the possible association of antidepressants with an increased risk of birth defects or congenital heart defects, few have examined the association between individual antidepressants and specific birth defects.

Here the authors, using data from the National Birth Defects Prevention Study, examined associations between individual antidepressants and specific birth defects. This was done with an attempt to account for potential confounding by underlying conditions, described in this analysis as “the condition necessitating treatment with an antidepressant as well as social and environmental factors associated with the condition.”

The study included 30,630 mothers of infants with birth defects (case mothers), and 11,478 control mothers. Mothers participated in a computer-assisted telephone interview 6 weeks to 24 months after their estimated date of delivery.

Antidepressant use early in pregnancy was reported by 5.1% of case mothers and 4.1% of control mothers, with sertraline, fluoxetine, paroxetine, citalopram, escitalopram, venlafaxine, and bupropion the most common antidepressants.

The authors observed elevated adjusted odds ratios (aORs) for selective serotonin reuptake inhibitors (SSRIs) and specific congenital heart defects. For example, mothers who used paroxetine or fluoxetine in early pregnancy had the highest proportion of elevated aORs with specific birth defects, followed by citalopram and sertraline. However, there were no elevated aORs between the fifth SSRI escitalopram, and specific birth defects.

Mothers who used venlafaxine had elevated aORs for multiple defects, while there were also elevated aORs for bupropion and three specific defects.

The association between SSRIs and heart effects was somewhat reduced when accounting for underlying conditions. For example, the association between fluoxetine and anomalous pulmonary venous return (aOR, 2.56; 95% CI, 1.10-5.930 was attenuated after partially accounting for underlying conditions (aOR, 1.89; 95% CI, 0.56-6.42). While this pattern persisted for most SSRI-congenital heart defect combinations, the authors pointed out there were 2 exceptions — fluoxetine with coarctation of the aorta and citalopram with atrioventricular septal defect.

“Our findings suggest that the elevated associations between heart defects and antidepressants may be confounded by the underlying condition,” Anderson and colleagues observed.

As for associations between SSRIs and non-congenital heart birth defects, the authors found that many persisted or strengthened after accounting for underlying conditions. And in the case of venlafaxine its association with multiple defects persisted after accounting for underlying conditions, and in some cases, such as anencephaly and craniorachischisis (aOR, 9.14; 95% CI, 1.91-43.83), the strength of that association increased.

The authors suggested that their findings highlight the need for further research on the relative reproductive and fetal safety of all first-line antidepressants.

“For women who require antidepressants during pregnancy, relative differences in the safety of specific medications may be useful to consider in risk-benefit decision-making,” Anderson and colleagues concluded. “Fully informed decision-making requires balancing the risks and benefits of any proposed intervention against the maternal and fetal risks of untreated depression or anxiety, mindful that with every pregnancy an underlying risk of a birth defect exists regardless of antidepressant treatment.”

In an editorial accompanying the study, Katherine L. Wisner, MD, MS, Northwestern University School of Medicine, Chicago, Illinois, and colleagues wrote that research needs to advance the sophistication of treatment decision-making by addressing a number of questions.

For example, if SSRIs treat maternal depression to the point of remission, does that improve reproductive outcomes improved compared with exposed women who remain symptomatic? And should research focus on discovering potential maternal-fetal benefits of pharmacotherapy, as well as the risks?

“Only when we effectively define and communicate scientific evidence of benefit-risk tradeoffs to pregnant women and clinicians will we improve outcomes for this vulnerable population,” wrote Wisner and colleagues.

  1. While there is an association between maternal antidepressant use and birth defects, that association is attenuated in some cases when adjusting for underlying conditions, particularly in the case of selective serotonin reuptake inhibitors (SSRIs) and specific congenital heart defects.

  2. Venlafaxine was associated with the highest number of defects, and that association persisted when accounting for underlying conditions.

Michael Bassett, Contributing Writer, BreakingMED™

Wisner is supported by HD085601-Obstetric-Fetal Pharmacology Research Center.

Cat ID: 41

Topic ID: 83,41,730,41,192,55,921