Depression threatens the health and well-being of pregnant women and their
unborn children, but antidepressant treatment carries its own risks.
Researchers struggle to better understand the risks associated with
antidepressant medications to pregnant women and unborn children and help
patients and physicians make individualized decisions.
In a study published online in AJP in Advance on March 16,
Katherine Wisner, M.D., and colleagues found that pregnant women with
continuous untreated depression and those with continuous exposure to
selective serotonin reuptake inhibitors (SSRIs) had similarly elevated rates,
of more than 20 percent, of preterm delivery (see chart). These rates were
significantly higher than the 4 percent to 9 percent preterm delivery rates in
women with SSRI exposure or depression without treatment during only part of
the pregnancy. The rates in women with exposure and depression during only
part of the pregnancy were not significantly different from those of the
control group of women with neither depression nor SSRI exposure.
All study participants had a diagnosis of depression, but symptom severity,
measured by the Hamilton Rating Scale for Depression, was significantly higher
in the group who had continuous depression with no SSRI treatment during
pregnancy than in the other
"The proportions of late (>34 to 37 weeks) and early (<34
weeks) preterm births were similar ... in women exposed to either continuous
major depressive disorder or continuous SSRI treatment throughout
pregnancy," Wisner, a professor of psychiatry, obstetrics, gynecology,
and reproductive sciences and epidemiology at the University of Pittsburgh
School of Medicine, told Psychiatric News. She is also the director
of the Women's Behavioral HealthCARE program at the Western Psychiatric
Institute and Clinic of the University Pittsburgh Medical Center.
"Either there is a factor related to the underlying disorder,
depression, that increases the risk for preterm birth regardless of whether
the depression is treated or not," Wisner explained, "or a factor
related to SSRI exposure, which differs from that related to untreated
depression has an equivalent impact on increasing preterm birth."
"The clinical implication is that a woman [with depression] who
declines antidepressant treatment because she is concerned about preterm birth
is at a similar risk because of the disease state," she noted.
Furthermore, most other clinical outcomes for the infants did not differ
significantly by in utero exposure to SSRIs or depression without treatment.
The clinical outcomes of infants, including physical anomalies, birth weight,
admission to neonatal intensive care units, and clinical assessments were also
similar among the mothers regardless of exposure to SSRIs. Of the assessed
clinical risks, only having an Apgar score above 7 at five minutes after birth
was significantly higher in the group with continuous SSRI exposure than in
the other groups. This study also found no association between SSRI exposure
and maternal weight gain.
The study researchers prospectively followed 238 pregnant women through
their pregnancy and delivery and compared those who had no depression and took
no SSRI (n=131), those who took SSRI either continuously or during part of the
pregnancy (n=71), and those who had major depressive disorder and took no SSRI
during the pregnancy (n=36). The analyses were based on assessments conducted
at weeks 20, 30, and 36 of the pregnancy, at delivery, and two weeks after
Previous studies have produced inconsistent results. Some evidence suggests
that exposure to SSRIs during pregnancy, especially in the late stage, may be
associated with increased likelihood of poor clinical outcomes for newborns.
Research also suggests that different SSRIs may have different pregnancy
risks, and paroxetine and fluoxetine have been most frequently associated with
problems in mothers and newborns, the authors noted.
In another study published online in AJP in Advance on January 2,
Sengwee Toh, M.Sc., of the Harvard School of Public Health and colleagues
identified a link between SSRI exposure in late pregnancy and a significantly
higher risk for gestational hypertension and preeclampsia. The authors
cautioned, however, that the study did not determine the cause and effect in
This retrospective study was based on survey data from nearly 6,000
Massachusetts women who gave birth between 1998 and 2007 and who participated
in a large surveillance program for birth defects. The authors acknowledged
that they could not have differentiated among the effects of the medications,
the mood disorders, and perhaps an interaction of both, because they compared
women taking SSRIs and not taking SSRIs during pregnancy without information
on their diagnoses.
It is notoriously difficult to determine the cause and effect between
pregnancy outcomes and specific medications since randomized, controlled
clinical trials cannot be conducted ethically in this context. Physicians and
patients have to make decisions based on available data from animal
experiments, epidemiological surveillance, and observational studies.
Further complicating the matter is the fact that depression, the risk of
which is increased by pregnancy, can have a detrimental effect on the health
behaviors of the mother, such as smoking, drinking alcohol, poor nutrition,
and poor self-care, which pose health risks to the fetus. The biological
effects of the underlying depressive disorder on pregnancy are still poorly
"In medicine, we typically focus more on the risks of medications
used to treat disorders than on [the risks of] the disorders themselves during
pregnancy," Wisner emphasized. The good news, however, is that "we
now know more about antidepressants during pregnancy than most other classes
The Wisner study was funded by grants from the National Institute of Mental
Health. The Toh study, conducted by researchers at the Slone Epidemiology
Center and the pharmacoepidemiology program at the Harvard School of Public
Health and the Department of Pediatrics at the University of California, San
Diego, was not directly funded by any organization or company.
"Major Depression and Antidepressant Treatment: Impact on
Pregnancy and Neonatal Outcomes" is posted at<http://ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2008.08081170v1>."
Selective Serotonin Reuptake Inhibitor Use and Risk of Gestational
Hypertension" is posted at<ajp.psychiatryonline.org/cgi/reprint/appi.ajp.2008.08060817v1>.▪