In a recent retrospective cohort study, data collected from linked records from the Women's and Children's Health Network in South Australia were used to investigate neonatal outcomes in children exposed prenatally to selective serotonin reuptake inhibitors (SSRIs). Women were included in this study if they gave birth to a singleton, live-born infant between September 2000 and December 2008 (n = 33,965).
Over the past few years, there have been a large number of studies which have relied on large administrative databases to generate information on the reproductive safety of various medications. One of the strengths of this type of approach is that it provides an opportunity to observe outcomes in a large number of subjects; however, there are certain, very important limitations. A recent study published in the American Journal of Obstetrics and Gynecology helps to understand some of the challenges in interpreting the data generated from these studies.
Selective serotonin and serotonin-norepinephrine inhibitors (SSRIs and SNRIs) have been shown to be effective for the treatment of hot flashes. However, these agents may carry certain side effects, including sexual side effects and sleep disturbance. These two side effects may be particularly concerning to peri- and postmenopausal women who, in addition to having vasomotor symptoms, are more likely to experience sexual dysfunction and sleep disruption than premenopausal women.
Recent reports suggest that people with lower folate levels are at higher risk of major depression or may experience more severe depressive symptoms. Other studies indicate that in folate deficient patients, antidepressants may be less effective or may take longer to take effect. In addition, some clinical trials have shown that folate may have a therapeutic effect on depression, either when taken alone or in combination with an antidepressant.
Multiple studies have demonstrated an increased risk of poor neonatal adaptation associated with exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants in late pregnancy. Results in the literature consistently indicate that about 25%-30% of infants exposed to SSRIs late in pregnancy manifest symptoms of poor neonatal adaption, including jitteriness, restlessness, increased muscle tone, rapid breathing. These symptoms are transient, resolving spontaneously with no specific medical intervention.
In 2006, Chambers and colleagues published an article linking SSRI use during late pregnancy to an increased risk of persistent pulmonary hypertension in the newborn (PPHN). Since that time, several other reports have been published which have examined the association between SSRI antidepressants and PPHN. Here is a summary of the findings to date:
Our Perinatal and Reproductive Psychiatry team often discusses clinical cases in Rounds, a confidential forum in which we can get advice and consultation from peers who also work in the area of Women's Mental Health. We discussed a patient's situation recently that highlighted the controversial area about how to prevent mood episodes in a woman planning for pregnancy.
Most obstetricians are now familiar with the potential for what has become known as neonatal distress syndrome (or "adaptation" syndrome) following third trimester exposure to SSRIs. Some patients still worry about the possibility of their baby developing neonatal distress syndrome, especially if anything unusual happened during the post-delivery experience of an earlier pregnancy. Women may be concerned about whether and to what degree the medication they were on played a role in their infant's distress and whether to continue that medication during a subsequent pregnancy. The following case may help illustrate the decision-making dilemmas.
While some side effects such as nausea, dizziness, and headaches associated with selective serotonin reuptake inhibitor (SSRI) antidepressants tend to decrease or resolve over time, other side effects such as sexual dysfunction rarely remit spontaneously. Treatment of sexual side effects in women is especially important when about 30-70% of patients taking antidepressants may experience sexual side effects, combined with the fact that women are prescribed antidepressants at rates of 2 to 1 when compared to men.
In 2006, Chambers and colleagues published an article linking SSRI use during late pregnancy to an increased risk of persistent pulmonary hypertension in the newborn (PPHN). Based on the results of this analysis, the authors estimated the risk of PPHN to be about 1% in infants exposed to SSRIs late in pregnancy (after 20 weeks). However, subsequent studies did not demonstrate a significant association between PPHN and SSRI usage. A new study, this one relying upon data from the Swedish Medical Birth Register, has observed an elevated risk of PPHN among SSRI-exposed infants.
