Antidepressants in Pregnancy: Good News, Bad News

Nancy A. Melville

August 13, 2015

Women receiving antidepressants during pregnancy are at reduced risk for preterm birth and cesarean delivery compared with women who have psychiatric disorders that are untreated. However, the drugs are also associated with an increased risk for adverse neonatal effects, new research shows.

"While our results differ from previous studies and were therefore somewhat unexpected, they provide novel evidence for a protective role of selective serotonin reuptake inhibitors [SSRIs] on deleterious pregnancy outcomes, including preterm birth, possibly by reducing maternal depression symptoms," lead author Heli Malm, MD, PhD, a specialist in obstetrics and gynecology at HUCH Teratology Information Service, in Helsinki, Finland, told Medscape Medical News.

The findings were published online August 4 in the American Journal of Psychiatry.

Individualized Approach Needed

The population-based study involved a sample of 845,345 singleton births in Finland between 1996 and 2010. Among the pregnancies, 15,729 involved exposure to SSRIs, 9652 involved mothers with psychiatric disorders who were not exposed to SSRIs, and a control group of 31,394 mothers who had no psychiatric diagnoses and who were not exposed to medications.

Compared with mothers with mental health disorders who were not treated with SSRIs, mothers who were treated had a 16% lower risk for late preterm birth (odds ratio [OR] = 0.84; 95% confidence interval [CI] = 0.74 - 0.96), a nearly 50% lower risk for very preterm birth (OR = 0.52; 95% CI = 0.37 - 0.74), and a 30% lower risk for cesarean delivery (OR = 0.70; 95% CI = 0.6620.75).

The findings remained consistent when the authors looked at women who had two or more SSRI purchases, which was interpreted to indicate consistent use of the medication.

As has been demonstrated in previous research, the study did show an increased risk for neonatal complications in mothers who used SSRIs compared with untreated mothers, including the risk for a low Apgar score (OR = 1.68; 95% CI = 1.34 - 2.12) and an increase in the need for monitoring in a neonatal care unit (OR = 1.24; 95% CI = 1.14 - 1.35).

For mothers with mental illness, both those who were treated with SSRIs and those who were not were at greater risk for adverse neonatal problems and for undergoing cesarean section compared with unexposed mothers who were without psychiatric disorders.

The authors speculated that the higher rates of neonatal complications observed in the SSRI group could, in part, be the result of a heightened awareness of the increased risk with SSRIs.

"It is possible that increased vigilance based on the knowledge that the mother had been treated with an SSRI led to increased identification of neonatal maladaptation in the SSRI-exposed group," the investigators write.

Delving into the possible mechanisms for how treatment of depression could improve pregnancy outcomes, the authors speculated on the known complications of depression-related stress.

"Prenatal stress, associated with maternal depression, affects regulation of the hypothalamic-pituitary-adrenal axis, resulting in increased corticosteroid production and release of vasoactive amines, potentially reducing umbilical blood flow and predisposing to hypoxia and preterm birth," the authors add.

"Hence, the protective effect observed in our cohort could be related to relief of symptoms and stress secondary to the antidepressant effect of SSRIs, and it may be consistent with the increased risk of preterm birth in mothers with untreated depression, which was also observed in our study."

The study found no increased risk for congenital anomalies or hypertension, including preeclampsia, in the group that used SSRIs compared with either of the comparison groups.

The risk for hypertension became "marginally significant" among women with two or more SSRI purchases; however, the effect, as seen in previous studies, was not major, the authors say.

The findings raise important questions of whether the benefits in the treatment of maternal depression outweigh the risks for neonatal effects, Dr Malm said.

"While the neonatal symptoms are usually short-lived, they can in individual cases persist longer and even require medication."

"On the other hand, preterm birth is a potentially serious condition and the most important cause of neonatal and infant death, and is also associated with neurological disabilities in surviving infants."

"While direct comparison of the severity of the outcomes may be difficult, the divergent findings suggest that the decision whether to prescribe an SSRI during pregnancy should always be individualized to the mother's medical and reproductive history."

Complicated Issue

Jeffrey L. Ecker, MD, director of obstetrical clinical research and quality assurance at Massachusetts General Hospital, in Boston, commented that although the research is well done, a wide range of potential confounders could play a role in the findings.

"The challenge in all of this research is knowing what's really different among the groups," Dr Ecker, who is chair of the American College of Obstetrics and Gynecology's Committee on Obstetric Practice, told Medscape Medical News.

"In terms of their depression and mental illness, those who have a diagnosis and are on medication may be different in some ways from those with a diagnosis and are off medications, and another important factor is body mass index, which can influence the risk of preterm birth and cesarean delivery."

"So the study showed these associations, but one can't jump to cause and effect here," he said.

The benefits of the antidepressants to the mothers themselves also need to be considered, Dr Ecker added.

"The study doesn't discuss issues such as the outcomes if women were to go off of the medications. Presumably, women are on these medications because they need to be for important reasons, so it's important not to ignore that," he said.

"Overall, I think it's a complicated picture. The data are uncertain, and providers need to have careful discussions with their patients about the issue."

The study received support from NIH grant P50MH090966. Study coauthor David Gyllenberg, MD, PhD, has received research grants from the Sigrid Juselius Foundation, the Foundation for Pediatric Research (Finland), and the Finnish Medical Foundation. Dr Malm, the other authors, and Dr Ecker report no relevant financial relationships.

Am J Psychiatry. Published online August 4, 2015. Abstract

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