Antidepressants during pregnancy: Confirmed safety of sertraline
This study provides reassuring evidence on the use of sertraline during pregnancy. The use of paroxetine or fluoxetine in early pregnancy has been associated with birth defects more frequently.
The use of SSRIs has been increasingly common among women of reproductive age and during pregnancy. SSRIs are used to treat depression and other mental health disorders. Due to inconsistent reports of the association between maternal SSRI use and birth defects of infants, there are limited opportunities for clinicians to carefully evaluate the risk compared with benefit of specific SSRIs for a given patient during pregnancy.
After initial reports of the association between maternal use of paroxetine and newborn heart defects, whether using antidepressants during pregnancy, especially SSRIs, could lead to birth defects in infants has been a topic of much discussion in recent years.1 Even the recent meta-analyses and systematic reviews, which combined data from more than 20 epidemiological studies, have derived conflicting conclusions. Consequently, the safety of antidepressant and its use in pregnancy are uncertain.2
This study reviewed the literature reports that assessed the relation between specific SSRIs and one or more of the specific birth defects that are also included in the NBDPS, and provided a more robust estimate of the association between individual SSRIs and birth defects.2 This information is necessary for patients who are being treated with these drugs and their physicians for making more optimal treatment decision.
This study used Bayesian methods to summarize the independent findings identified in the literature and to update those findings using the entire set of data from NBDPS, a population-based and case-control study of birth defects in the United States (US).3 The study authors considered women exposed if they took citalopram, escitalopram, fluoxetine, paroxetine, or sertraline at least once in the period from one month before conception to the third month of pregnancy.4 Mothers were interviewed to assess if they had any illnesses other than the ones already discussed (for example, hypertension or diabetes) and whether they took any medications for the illness. No specific question addressed depression, but they could report depression on any other diseases they are suffering from, which would then be followed by a question about any medications taken for the illness.3 Briefly, cases of birth defects were identified through the birth defects surveillance systems in ten states of US.
The primary intent of this analysis was to assess previously reported associations of birth defects with SSRIs and to determine if those associations were supported by NBDPS data. At least one previous report of birth defects, such as neural tube defects, anencephaly, all septal defects, ventricular septal defects, right ventricular outflow tract obstructions, cleft palate, cleft lip with or without cleft palate, esophageal atresia, anal atresia, hypospadias, any limb reduction defect, craniosynostosis, gastroschisis, and omphalocele, in the peer reviewed literature suggesting a possible association with SSRIs was included in this study.4
A total of 38,009 women with births between 1997 and 2009 were interviewed for the NBDPS. Women reporting pre-existing diabetes (n=719), known use of teratogenic drugs (n=65), or depression, anxiety, bipolar disorder, or obsessive-compulsive disorder but not reporting any antidepressant use (n=30), were excluded. And after excluding defects with no previous reported associations with SSRIs, the final analyses included 17,293 unexposed cases, 659 cases exposed to citalopram, escitalopram, fluoxetine, paroxetine or sertraline, and 9,559 unexposed controls. (Table 1).4
Results and discussion
The most commonly used SSRI in the study was sertraline; approximately 40% of control mothers who reported the use of sertraline as their choice of SSRI followed by fluoxetine (25%), paroxetine (14%), citalopram (10%), and escitalopram (9%) (Table 2).4 The distribution of specific SSRIs was similar across the study sites. There was no difference in the age distribution among SSRI users, except for sertraline, which was more often reported among older mothers. The use of citalopram and escitalopram was initially reported in 2000 and 2002 respectively and increased over time. While sertraline use stays relatively constant, the use of fluoxetine and paroxetine has decreased over time. The decrease of paroxetine was at a significantly higher rate than fluoxetine.4
There was no association with maternal use of escitalopram monotherapy and birth defects. A marginal association between citalopram and neural tube defects was observed (Table 3).4 However, fluoxetine treatment was associated with ventricular septal defects, right ventricular outflow tract obstruction cardiac defects, and craniosynostosis. Paroxetine had the highest number of previously reported associations, and significant associations were observed for five of the seven previously reported defects. Associations between paroxetine and anencephaly, atrial septal defects, and right ventricular outflow tract obstruction cardiac defects were confirmed in this independent Bayesian analysis and two other associations with gastroschisis and omphalocele seen in the previous NBDPS analysis were confirmed again in this analysis. Most importantly, for sertraline, the most commonly used SSRI in the study, the findings of all five previously reported defects were not significant.
The lead authors of the study Dr. Jennita Reefhuis, Research Health Scientist, Centre for Disease Control and Prevention, Atlanta, Georgia stated that the focus of this study was to prevent major birth defects while providing adequate treatment for depression and other mental health disorders in pregnant women. A major advantage of this analysis over some previous reports is the ability to assess individual SSRIs and birth defects, while accounting for earlier reported associations.
Dr. Reefhuis emphasized, “40% of women who did not experience birth defects in infants reported using sertraline in early pregnancy,” and further explained, “We did not observe any previously reported birth defects in infants whose mothers reported having sertraline.” She also pointed out that women who reported fluoxetine or paroxetine use were at 2 to 3 times higher risk of having infant birth defects. However, the study warrants continuous scrutiny of the association between SSRIs and birth defects, and additional studies of specific SSRI treatments during pregnancy and birth defects are needed to enable women and their healthcare providers to make more informed decisions about treatment. Dr. Reefhuis concluded, “The current analysis can help guide the healthcare providers and women to the safest options for the treatment of depression during early pregnancy.
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