Safety of SSRIs in Pregnancy

Dr Sian-Lee Ewan, GPST2, Northern Ireland Deanery
doi:10.7244/cmj.2013.07.003


A recent study, Jensen et al 2013 [1], sought to differentiate the effects of exposure to maternal depression from the effects of antidepressants in their contribution to a reduction of Apgar scores. They collected data regarding diagnosis of depression, use of antidepressants in pregnancy, and Apgar scores at 5 minutes from all pregnancies in Denmark from 1996 to 2006 using national databases. This gave information on 668,144 births. Pregnant women were divided into 8 risk groups depending on their exposure to antidepressants during pregnancy, their exposure to antidepressants before pregnancy, and a diagnosis of depression before the end of pregnancy. Logistic regression analyses were applied with Apgar score <7 as the outcome and risk group as the variable of interest. Apgar score of <7 at 5 minutes was used as the outcome because it has been associated with an increased risk of low IQ at age 18, individuals being less likely to have no income from work, and neurological disability [1].Mental health in pregnancy remains a significant issue, with 7-13% [1] of women experiencing depressive symptoms during pregnancy. ‘Confidential Enquiries into Maternal Deaths in the United Kingdom’ [2] have highlighted suicide in pregnancy and during the first postnatal year as a leading cause of maternal death. SSRIs are known to cross the placental barrier, however the safety of these drugs in pregnancy is not well understood [3]. In the NICE guidelines, the only documented risk regarding SSRIs in pregnancy (excluding paroxetine), is neonatal persistent pulmonary hypertension if antidepressants are taken after 20 weeks gestation. Previous studies have shown an association between pregnant women suffering from depression and taking antidepressants with low Apgar score in infants [1]. However, there is little evidence whether this association is attributable to antidepressants or the depressive illness.

Results showed that Apgar scores were reduced in infants exposed to antidepressants during pregnancy (Odds Ratio 1.72, 95% CI 1.34-2.2). There was no associated reduction in Apgar scores where the mother suffered from depression but did not take antidepressants (OR 0.44, 95% CI 0.11-1.77). Further analyses of classes of antidepressants revealed that only SSRIs had a statistically significant risk of low Apgar scores (OR 1.96, 95% CI 1.52-2.54). There was no association with tricyclic antidepressants or newer antidepressants (e.g. mirtazepine or venlafaxine).

This study concluded that SSRI use in pregnancy increases the risk of a low Apgar score independent of the depressive illness. They showed a 70% increased risk of low Apgar scores when SSRIs were used during pregnancy compared to healthy women. However the absolute prevalence remains low at 1.14%. The main strengths of this study lie in the large sample size and the data collection. Data was collected from databases were it had been originally recorded prospectively, thus eliminating recall bias. One limitation of this study is that they did not account for the severity of depression. Women in the risk group who took antidepressants, are more likely to have a more severe form of depression than those with depressive symptoms not using antidepressants. Furthermore, they did not account for mode of delivery or use of analgesia during labour which could be confounding factors. In spite of this, the statistical findings are specific to SSRI antidepressants, which further support their conclusions. Further directions for research could include looking at the trimester of SSRI use in relation to reduced Apgar scores, and efforts to account for the severity of depression. Despite the limitations of this study, these results add further evidence to a difficult area of prescribing which will be useful when counseling patients.

References: 

1. Jensen HM, Randi G, Lidegaard O, Pedersen LH, Andersen PK, Kessing LV. Maternal depression, antidepressant use in pregnancy and Apgar scores in infants. The British Journal of Psychiatry. 2013; 202:347-351 doi:10.1192/bjp.bp.112.115931
2. Centre for Maternal and Child Enquires (CMACE). Saving Mothers’ Lives: reviewing maternal deaths to make motherhood safer:2006-2008. The Eighth Report on Confidential Enquires into Maternal Deaths in the United Kingdom. BJOG. 2011; 118(Suppl. 1):1-203. doi:10.1111/j.1471-0528.2010.02847.x
3. NICE. Antenatal and Postnatal Mental Health. NICE 2007; clinical guideline 45. Available atwww.nice.org.uk/CG45