[Physician Comment] SSRI use during pregnancy not associated with fetal, neonatal or infant mortality

Jan 5th – Selective serotonin reuptake inhibitor (SSRI) use during pregnancy was not associated with increased risk of stillbirth, neonatal mortality, or post-neonatal mortality.[tabs tab1=”2MM Rundown” tab2=”Full 2MM Report” tab3=”About the Authors”]

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1. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy was not associated with increased risk of stillbirth, neonatal mortality, or post-neonatal mortality.

2. For some women, the risks associated with uncontrolled maternal mental illness may outweigh the risks associated with maternal SSRI use.

Intrauterine SSRI exposure was not associated with increased risk of stillbirth, neonatal death or post-neonatal death. This is the largest study to evaluate the association between peripartum SSRI use and the risk of stillbirth or infant death.

This study is limited by retrospective analysis as well as the method of exposure classification, which may have biased results toward the null hypothesis due to the assumption that a filled SSRI prescription was a reliable surrogate for SSRI use. Strengths include prospectively collected data and a large sample size that allowed for adequate power even in multi-variate models and in stratified subanalyses, a limitation of previous studies on this topic.

Click to read the study in JAMA

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1. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy was not associated with increased risk of stillbirth, neonatal mortality, or post-neonatal mortality.

2. For some women, the risks associated with uncontrolled maternal mental illness may outweigh the risks associated with maternal SSRI use.

Study author, Dr. Olof Stephansson MD, PhD, talks to 2 Minute Medicine: Karolinska Institutet, Stockholm, Sweden:

“Depression is associated with stillbirth and infant mortality, but this is not necessarily due to SSRI use. Students should be aware that maternal depression and psychiatric disease of any kind should be considered high-risk pregnancies, which may need extra attention. It is also important to know that women with these diseases may need medication during pregnancy, which is why studies like ours are so important. The pregnant woman should discuss her medication with her doctors and try to use the lowest dose possible. We cannot test drugs on pregnant women, but we can use epidemiological tools to look afterwards and compare women taking these drugs with women who are not.”

Primer: Depression is related to decreased levels of the neurotransmitter serotonin; SSRIs, the most popularly prescribed antidepressants, block the reabsorption of serotonin from the synaptic cleft, allowing for more activation of receptors on the post-synaptic neuron (1,2).

Women are more likely than men to get depression. In reproductive age women seeking conception, medical management of depression is a major concern because while medications can pose risks, untreated depression also comes with risks to both mother and fetus. Untreated depression is associated with considerable maternal morbidity and mortality (suicide) and poses risks to the fetus in the form of maternal noncompliance with prenatal recommendations such as exercising proper nutrition and restricting the use of alcohol, cigarettes and various mood-altering substances (2,3).

Given the risks, it is often recommended that women continue pharmaceutical management of moderate to severe depression throughout pregnancy, usually with SSRIs. However, SRRI use has been linked to adverse pregnancy outcomes, such as congenital anomalies, spontaneous abortion, and persistent pulmonary hypertension. Though, attempts to directly weigh the pros and cons of medical management of depression in pregnancy are complicated by the ethical limitations of conducting drug trials in pregnant women (3,4,5,6).

This study evaluated rates of adverse perinatal outcomes (stillbirth, neonatal death and infant death) in women taking SSRIs as compared to healthy women.

Background reading:

1. Up-to-date: Depression in pregnant women, clinical features and consequences
2. Up-to-date: Depression in pregnant women, management
3. Up-to-date: Infants with antenatal exposure to SSRIs
4. FDA Drug Safety Communication: SSRI use during pregnancy and reports of a rare heart and lung condition in newborn babies
5. Depression and anxiety during pregnancy: a risk factor for obstetric outcome? A critical review of the literature
6. The management of depression during pregnancy: a report for the the American Psychiatric Association and the American College of Obstetricians and Gynecologists

This [retrospective population-based cohort] study: utilized prospectively collected data from the nationwide health registries of Nordic countries to identify 1,633,877 viable pregnancies. Of these, 29, 228 (1.7%) met criteria for maternal SSRI exposure, defined as 1 or more filled prescription from 3 months before pregnancy through birth. Primary outcomes were stillbirth (death at >22 weeks gestation), neonatal death (0-27 days post-birth) and post-neonatal death (28-364 days post-birth).

Multivariate regression models demonstrated no significant association between SSRI exposure and adverse perinatal outcomes. Compared to healthy women, women taking SSRIs experienced no increased risk for stillbirth, neonatal death, or post-neonatal death.

In sum: Intrauterine SSRI exposure was not associated with increased risk of stillbirth, neonatal death or post-neonatal death. This is the largest study to evaluate the association between peripartum SSRI use and the risk of stillbirth or infant death.

This study is limited by retrospective analysis as well as the method of exposure classification, which may have biased results toward the null hypothesis due to the assumption that a filled SSRI prescription was a reliable surrogate for SSRI use. Strengths include prospectively collected data and a large sample size that allowed for adequate power even in multi-variate models and in stratified subanalyses, a limitation of previous studies on this topic.

Click to read the study in JAMA

By [MS] and [LH]

More from this author: Vulvovaginal swabs more sensitive than endocervical swabs at detecting chlamydia, Bipolar Disorder is associated with adverse pregnancy outcomes regardless of pharmacologic treatment, No-cost contraception reduces unintended pregnancies

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Maren Shapiro: Maren is a 2nd year M.D. Candidate at the University of Pennsylvania.

Leah Hawkins: Leah is a 5th year M.D./MPH candidate at Harvard Medical School.

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