Research suggests only using lowest effective dose

While maternal depression during pregnancy has been shown to be associated with a number of adverse pregnancy outcomes, once antidepressant use in pregnant women increases beyond what is considered the lowest effective dose, it is associated with an increased risk neonatal respiratory distress, researchers found.

In addition, there is an increased risk of preterm birth among women who take moderate to high doses of antidepressants during pregnancy.

This retrospective study of prenatal antidepressant use and the risk of adverse neonatal outcomes was published in Pediatrics.

According to study authors Gretchen Bandoli, PhD, Department of Pediatrics, University of California, San Diego, and colleagues, untreated depression in pregnant women is associated with both maternal and offspring morbidity. However, while the use of pharmacologic — and nonpharmacologic — interventions is encouraged for these women, there is some uncertainty as to the association between prenatal antidepressant use and neonatal outcomes.

For example, some studies found that prenatal antidepressant use is associated with preterm birth, major cardiac malformations, and neonatal respiratory distress, while other studies have failed to confirm those findings. Bandoli and colleagues suggested that one reason for this discrepancy is that previous studies relied on broad categorizations of antidepressant use, which hinders how timing and dose actually affects neonatal outcomes.

Therefore, in this study the authors set out to estimate the risk of select neonatal complications associated with specific patterns of prenatal antidepressant use. They constructed a database of 226,932 births from 208,271 women using the OptumLabs Data Warehouse, which records medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees.

Bandoli and colleagues identified 15,041 (6.6%) pregnancies exposed to antidepressants in the period between the woman’s last menstrual period and 35 gestational weeks. Outcomes included major cardiac malformations (11.7 of 1,000 births), preterm birth (75.7 of 1,000 births), and newborn respiratory distress (54.2 of 1,000 births).

Sertraline (32.4%) was the most commonly filled antidepressant, while citalopram, fluoxetine, escitalopram, and bupropion each accounted for 13% of antidepressant prescriptions.

The authors divided use patterns into 5 categories — low use (∼10 mg/day) with first-trimester reduction; low sustained use (∼20 mg/day); moderate use (∼40 mg/day) with first-trimester reduction; moderate sustained use (∼40 mg/day), and high sustained use (∼75 mg/day).

Bandoli and colleagues found that:

  • Moderate sustained (adjusted risk ratio [RR] 1.31; 95% confidence interval [CI] 1.16-1.49) and high sustained (adjusted RR 1.78; 95% CI 1.48-2.14) use trajectories resulted in an increased risk of preterm birth.
  • Pregnancies exposed to moderate, sustained antidepressant use had an increased risk for major cardiac malformations relative to the lowest trajectory (2.4% versus 1.5%; adjusted RR 1.6 [95% CI 1.2-2.3]).
  • Compared with the lowest trajectory group, the other four trajectory groups had an elevated risk of neonatal respiratory distress (adjusted RRs 1.36 [95% CI 1.20-1.50] to 2.23 [95% CI 1.83-2.77]).

The authors cautioned that they couldn’t rule out confounding by disease severity as an explanation of these results.

“Our findings support the continued use of the methodology to further delineate risk by different patterns of antidepressant use,” Bandoli and colleagues concluded. “This approach can help clinicians counsel pregnant women on the use of antidepressants during gestation. In addition, it can help to identify groups whose infants may be at higher risk for preterm birth or neonatal respiratory distress.”

In a commentary accompanying the study, Sascha Dublin, MD, PhD, Kaiser Permanente Washington Health Research Institute, Seattle, Washington, and colleagues observed that while the current study was “thorough and thoughtful,” it illustrates key challenges in this field.

Dublin and colleagues argued that in order to answer questions about medication exposure in pregnancy researchers need substantially larger databases than they have been able to construct at this point. They further pointed out that while databases of 600,000 to 2 million births may be considered large, “these sample sizes may not be adequate to assess relatively rare exposures and outcomes of interest.”

In the current study, for example, Dublin and colleagues noted that while about 15,000 pregnancies were exposed to antidepressants, just 434 were associated with high-dose exposure — sample sizes “too few to draw meaningful conclusions.”

“To solve this problem, we must implement new structures and policies that incentivize collaboration and data sharing,” wrote Dublin and colleagues. “We need bold visions, funding mechanisms, and governance policies to stimulate and support large transnational consortia that can generate data sets of 10 to 20 million pregnancies.”

  1. The use of antidepressants beyond the lowest effective dose in pregnant women is associated with an increased risk of neonatal respiratory distress.

  2. There is an increased risk of preterm birth in women who are catergorized as high-use users of antidepressants.

Michael Bassett, Contributing Writer, BreakingMED™

The authors had no relationships to disclose.

Cat ID: 41

Topic ID: 83,41,730,41,138,192,925