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Antidepressant use in pregnancy linked to higher risk for psychiatric disorders

An analysis of data from Danish national registers has linked in utero exposure to antidepressants with increased risk for psychiatric disorders. However, researchers cautioned that these findings may be due to the severity of maternal psychiatric disorders.

“Antidepressants have been increasingly used during pregnancy in the past few decades, with approximately 2% to 8% of pregnant women receiving this treatment,” Xiaoqin Liu, MD, PhD, of Aarhus University, Denmark, and colleagues wrote. “Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. Although most studies on the safety of SSRI treatment during pregnancy are reassuring, some recent studies have raised concerns about behavioral problems in the offspring.”

To assess associations between in utero exposure to antidepressants and risk for psychiatric disorders, researchers analyzed data from Danish national registers for 905,383 liveborn singleton births from 1998 to 2012 in Denmark. Children were followed for a maximum of 16.5 years.

Study participants were categorized into four groups based on maternal antidepressant use within 2 years before and during pregnancy: unexposed; antidepressant discontinuation (use before but not during pregnancy); antidepressant continuation (use before and during pregnancy); and new user (use only during pregnancy).

Overall, 32,400 participants were diagnosed with psychiatric disorders.

Adjusted 15-year cumulative incidence of psychiatric disorders was 8% (95% CI, 7.9-8.2) among unexposed participants; 11.5% (95% CI, 10.3-12.9) in the antidepressant discontinuation group; 13.6% (95% CI, 11.3-16.3) in the continuation group; and 14.5% (95% CI, 10.5-19.8) in the new user group.

Participants in the antidepressant continuation group had increased risk for psychiatric disorders compared with the discontinuation group (HR = 1.27; 95% CI, 1.17-1.38).

According to the researchers, the observed association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. “The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive,” the researchers concluded.

In an accompanying editorial, Hedvig Nordeng, MSc, DPhil, of the University of Oslo, and colleagues wrote that understanding the reproductive safety of drugs requires consideration of long-term neurodevelopmental outcomes.

“Observational studies, for all their flaws, are a necessary piece of the puzzle,” they wrote, “and healthcare databases such as the one used for this study provide a rich resource, particularly if they are augmented by additional data sources to reduce confounding. However, database and registry studies have limitations and must be supplemented by genetic and epigenetic studies, pharmacokinetic data, animal studies and in vitro research, which together can provide a more complete picture of the mechanisms by which drugs may act on the developing fetus.” – by Amanda Oldt

Disclosures: The authors report no relevant financial disclosures.