The extent to which antidepressant use during pregnancy is associated with increased risks of postnatal adaptation syndrome (PNAS), persistent pulmonary hypertension in the newborn (PPHN), first-trimester teratogenicity, stillbirth, and infant mortality is explored in 2 recent studies.1,2
In a recent interview, lead author Nancy Byatt, DO, MBA, a perinatal psychiatrist and Assistant Professor of Psychiatry and OB-GYN at the University of Massachusetts Medical School, said that depression and anxiety are very common during pregnancy and the postpartum period. Approximately 18.4% of women suffer from antenatal depression, and as many as 19.2% experience postpartum depression. In the third trimester, 1 of 5 women (21.7%) experiences anxiety disorders, and in the first 3 postpartum months, 11.1% have an anxiety disorder.1
In economically developed countries, the prevalence for depression during pregnancy ranges between 7% and 19%, according to obstetrician and epidemiologist Olof Stephansson, MD, PhD, of the Karolinska University Hospital Solna in Stockholm, who is also lead investigator on a recent study that assessed the relative risks of stillbirth and infant mortality associated with SSRI use during pregnancy.2
Byatt told Psychiatric Times that conflicting data have led to major controversies regarding antidepressant use during pregnancy. To help providers “understand the risks and benefits of using antidepressants during pregnancy and apply that knowledge to enhance clinical care,” she and colleagues conducted an extensive review of the literature between 1966 and 2012.
Antidepressants considered in the review included SSRIs, SNRIs, and norepinephrine reuptake inhibitors. According to Byatt, the review focused on outcomes that “have the most controversy surrounding them.” These are congenital malformations, PNAS, and PPHN.
“The current evidence for malformations is limited because of inconsistent findings and limited methodology of the published studies,” the review authors wrote. “Few studies have controlled for maternal illness, and therefore do not take into account whether reproductive outcomes are due to maternal illness or antidepressant exposure.”
“There are some individual studies that show a risk between specific SSRIs and birth defects, but if you look at the overall evidence, it has not been consistently observed, which is very reassuring,” Byatt said. “There has not been any single malformation that has been consistently observed across studies with any commonly used antidepressant.” The investigators concluded that PNAS occurs in up to 30% of neonates who are exposed to antidepressants in late pregnancy. But, it is a transient syndrome that typically resolves in days and in rare cases, a few weeks.
“The PPHN literature is limited by small and/or uncontrolled studies,” according to Byatt and her group. In addition, “there are other reported risk factors, including race, method of delivery, obesity, asthma, and diabetes that many studies do not take into account.” The evidence regarding the risk of PPHN because of in utero antidepressant exposure remains inconclusive. Some studies suggest a small association, and other studies suggest no association.
Byatt pointed to changes in drug safety advisories on SSRIs and PPHN over the years. In 2006, the FDA issued a Public Health Advisory warning of a possible link between SSRI antidepressant use during pregnancy and reports of PPHN. However, in 2011, the FDA, in a Drug Safety Communications, said that given conflicting results from different studies, it is “premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN.”
“Overall, we do not recommend discontinuing SSRIs in pregnant women because of the risk of PPHN,” Byatt said. The literature and her communications with other experts in the women’s mental health field indicate that “the overall data on SSRI use in pregnancies is reassuring. SSRIs are considered to be relatively safe for use during pregnancy and the postpartum period.” There are limited data regarding other classes of antidepressants. “The available studies are reassuring, but not definitive,” she said.
1. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand. 2013;127:94-114.
2. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013;309:48-54.
3. Nulman I, Koren G, Rovet J, et al. Neurodevelopment of children following prenatal exposure to venlafaxine, selective serotonin reuptake inhibitors, or untreated maternal depression. Am J Psychiatry. 2012;169:1165-1174.
4. Domar AD, Moragianni VA, Ryley DA, Urato AC. The risks of selective serotonin reuptake inhibitor use in infertile women: a review of the impact on fertility, pregnancy, neonatal health and beyond. Hum Reprod. 2013;28:160-171.
5. Kieler H, Artama M, Engeland A, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population-based cohort study from the five Nordic countries. BMJ. 2012;344:d8012.