Are Antidepressants Safe in Pregnancy?

Are Antidepressants Safe in Pregnancy?


Q.1: Is first-trimester use of SSRIs associated with increased risk of birth defects?

This study used the data from the Slone Epidemiology Center Birth Defects Study (an ongoing program of case–control surveillance of medications in relation to birth defects) to answer this question. 

  • This analysis DID NOT confirm previously reported associations between overall use of SSRIs and craniosynostosis, omphalocele, or heart defects as a group.
  • This analysis DID NOT replicate past findings of paroxetine association with omphalocele.
  • They DID NOT find significantly increased risks of congenital heart defects overall associated with overall use of SSRIs or of non-SSRI antidepressants.



  1. They did found doubling of the risk of septal defects associated with sertraline use (odds ratio, 2.0; lower confidence bound, 1.0), based on 13 exposed subjects.
  2. They found tripling of the risk of right ventricular outflow tract obstruction defects associated with paroxetine use (odds ratio, 3.3), based on 6 exposed subjects.


Source: N Engl J Med 2007; 356:2675-2683


Q.2: If antidepressants use during pregnancy is associated with an increased risk of congenital cardiac defects?

This is a cohort study nested in the nationwide Medicaid Analytic extract for the period 2000 through 2007 (cohort of 949,504 pregnant women).

  • They found NO significant increase in the risk of cardiac malformations among infants born to women who took antidepressants during the first trimester.
  • NO significantly increased risks were observed with respect to specific cardiac defects previously hypothesized to be associated with such drug use, specific antidepressant medication classes, or the most commonly used SSRIs.
  • Do NOT support earlier findings of an association between antidepressant use and cardiac anomalies, in particular findings with respect to the use of paroxetine and sertraline.


Source: N Engl J Med 2014; 370:2397-2407


Q.3: If maternal bupropion treatment in early pregnancy is associated with congenital heart defects?

This study gathered data since 2003 by the Slone Epidemiology Center’s Case-control Birth Defects Stud to answer this question. They found 8611 non-malformed infants and 7913 infants with cardiac defects.

  • They DID NOT confirm previously reported associations for left-sided defects overall but had too few exposed cases to evaluate specific defects in this category.
  • They DID observed an elevated risk of Ventricular Septal Defect following first-trimester bupropion use, particularly when used without other antidepressants.
  • This pattern for bupropion alone was observed in all our risk comparisons and was not explained by higher doses or gestational timing.


Source: Pharmacoepidemiol Drug Saf. 2014 Oct;23(10):1066-75.


Q.4: Does SSRI and SNRI use during pregnancy increases the risk of persistent pulmonary hypertension of the newborn?

This study used data from the Quebec Pregnancy Cohort between 1998 and 2009: 143 281 pregnancies were included.

  • Adjusting for maternal depression, and other potential confounders, SSRI use during the second half of pregnancy was associated with an increased risk of PPHN [adjusted odds ratio (aOR) 4.29, 95% CI 1.34, 13.77] compared with non-use of antidepressants.
  • SNRI use during the same time window was not statistically associated with the risk of PPHN (aOR 0.59, 95% CI 0.06, 5.62).
  • Use of SSRIs and SNRIs before the 20th week of gestation was NOT associated with the risk of PPHN.


Source: Br J Clin Pharmacol. 2016 Nov 22


According to FDA Drug Safety Warning (issued in 2012):

  • It is unclear whether SSRI use during pregnancy can cause PPHN, because the available data are conflicting.
  • Healthcare professionals must weigh the small potential risk of PPHN that may be associated with SSRI use in pregnancy against the substantial risks associated with under-treatment or no treatment of depression during pregnancy.




Q.5(a): Does prenatal antidepressant exposure results in poor neonatal adaptation syndrome (PNAS)?

Their is conflicting reports on potential risks of antidepressant exposure during gestation for the infant. This systematic review and meta-analysis answered this question.

  • There was a significant association between exposure to antidepressants during pregnancy and overall occurrence of PNAS (odds ratio [OR] = 5.07; 95% CI, 3.25-7.90; P < .0001).
  • Respiratory distress and tremors were also significantly associated with antidepressant exposure.
  • Neonatologists need to be prepared and updated in their management, and clinicians must inform their patients of this risk.


Source: J Clin Psychiatry. 2013 Apr;74(4)


Q.5(b): Does reducing exposure to SSRI’s at the end of pregnancy improves neonatal health?

This study used population health data, maternal health and prenatal SSRI prescriptions were linked to neonatal birth records (N = 119,547) (1998-2001).

  • Controlling for maternal illness severity, reducing exposure to SSRI’s at the end of pregnancy had NO significant clinical effect on improving neonatal health.
  • These findings raise the possibility that some adverse neonatal outcomes may not be an acute pharmacological condition such as toxicity or withdrawal.


Source: Acta Psychiatr Scand. 2010 Jun;121(6):471-9.

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Dr. Harvinder Singh, M.D. (Admin)

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