Infants Exposed to SSRIs May Experience Subtle Problems in Early Weeks of Life

As with most medications, pregnant women with major depressive disorder must weigh the pros and cons of taking antidepressants over the course of their pregnancy.

There is evidence to suggest that women with untreated depression may be at greater risk of delivering infants preterm or of lower birth weight. Other studies have found that the use of selective serotonin reuptake inhibitors (SSRIs) to treat depression during pregnancy can induce neurobehavioral challenges in the infants such as greater irritability, insomnia, and respiratory distress.

These challenges—collectively known as neonatal adaptation syndrome—are believed to be the result of withdrawal from fetal exposure to the medication and dissipate within two weeks after birth. Now a study published October 30 in AJP in Advance provides evidence that these early neurobehavioral problems associated with SSRIs can persist for at least 30 days after birth.

Although the findings suggest it takes longer for the effects of neonatal adaptation syndrome to pass, Amy Salisbury, Ph.D., an associate professor of pediatrics, psychiatry, and human behavior at Brown University and lead author of this study, pointed out that the observed symptoms are just exacerbations of standard infant behavior.

Nonetheless, Salisbury told Psychiatric News that the study does advance previous knowledge of neonatal adaptation syndrome. “First, it’s important to know how long neonatal adaptation syndrome lasts to help new mothers manage expectations; if they think these symptoms go away after two weeks but they don’t, it could worsen behavioral symptoms in the mothers during a very delicate postpartum period,” she said. “Second, the 30-day persistence suggests this syndrome is less a withdrawal profile than believed.”

Instead, Salisbury noted, the behaviors are more likely brought on by biological effects of the medication, for example, changes in serotonin signaling.

Salisbury and colleagues assessed pregnant women at two points during their pregnancy and classified them into four groups based on their psychiatric and medication status: no exposure (depression and medication free), depression only (no medication taken), SSRI exposure, and SSRI plus benzodiazepine exposure. All full-term infants (184 in total) were then given multiple neurobehavioral assessments during the first week after delivery, with follow-up assessments on days 14 and 30.

Infants in the SSRI and SSRI plus benzodiazepine groups had lower quality of movement and more central nervous system stress signs such as tremors during the first postnatal month compared with infants in the no-exposure and depression-only groups. In addition, infants in both SSRI groups showed lower self-regulation and higher arousal at day 14 compared with the other two groups.

Infants of mothers who took both SSRIs plus benzodiazepines had the least favorable scores on their neurobehavioral measures, though again Salisbury noted the scores were still in a stable range; for example, the movement quality for SSRI plus benzodiazepine infants averaged a 3.8 after 30 days (using the Neonatal Intensive Care Unit Network Neurobehavioral Scale), whereas typical babies average a little above 4.0 at this age.

But even though the changes were subtle, Salisbury noted that clinicians may want to raise the threshold at which depression symptoms in the mother warrant the use of polytherapy.

For those women taking only SSRIs, though, not much needs to change clinically, she said. “We did not find any differences in the behavior of infants whose mothers discontinued SSRIs in the third trimester compared with those who did not. So in agreement with current practice guidelines, these findings do not support SSRI discontinuation if women have been effectively managing their depressive symptoms.”

Salisbury noted that her research team is continuing to follow this cohort of infants (who are now 3 to 5 years old). They already have some behavioral data for the children at 18 months, which may be able to offer more insight into any long-term effects of SSRI use in pregnancy.

This study was supported by multiple grants from the National Institutes of Health. ■