Risks of antidepressant use in pregnancy: Acta Psych Scand. March 2013.


Up to  18 % women might be suffering from antenatal depression. 20% might have anxiety disorders during third trimester. Untreated depression is associated with preeclampsia, preterm birth , elective termination of the pregnancy  and postpartum depression and anxiety. Depression is  associated with fetal distress and an increased risk of neonatal care unit admission and caesarian delivery .Maternal depression may lead to  disability in children including cognitive delays, (Low IQ, delayed development) and behavioural problems. One-third of school-aged children of depressed mothers suffer from depressive, anxiety, or disruptive disorders. Treating depression in pregnancy is thus very important.

Antidepressants use in pregnancy is associated with many risks and controversies. Byatt N, Deligiannidis KM and Freeman MP reviews the main themes in this article.


In the USA, approximately 1 in every 33 infants (3%) is born with a major birth defect . However, the major birth defects studies in association with depression are rare.Across the various study types ( administrative data, drug registry, prescription data, prospective interview data, the risks of the underlying untreated disorder and other associated confounding factors are rarely taken into account.This makes the data available  difficult to interpret.

Paroxetine: GSK reported an increase in cardiac malformations in infants exposed to paroxetine in utero compared with controls.(unpublished/non peer reviewed report to FDA).Many studies hace since then reported this.The causality and magnitude of that risk is still unclear. Metanalysis suggest increased risk. (Bar-Oz B ,2007 & Wurst  2010). First-trimester paroxetine exposure is associated with an increased prevalence of combined cardiac defects [prevalence odds ratio (POR) = 1.46%; 95% CI 1.17–1.82].ASD and VSD are the cardiac defects reported.

SSRIs as a class:  Five meta-analyses have investigated the risk for major malformations in association with anti- depressant use during pregnancy. Four of these studies found no statistically significant increased risk of major malformations in the first trimester of pregnancy . The fifth meta-analysis found an increased risk of cardiac malformations in infants exposed to paroxetine in the first trimester . 

Other antidepressants: No definitive data regarding the reproductive safety of venlafaxine, trazodone, mirtazapine, and bupropion.The limited available data suggest a possible association between bupropion and congenital heart defects , the absolute risk appears low. 

Postnatal adaptation syndrome (PNAS) : First reported in 1973. This manifest as irritability, tachypnea, hypothermia, and hypogly- cemia usually develop from birth to days after delivery and are time limited.  mechanisms proposed for PNAS include serotonin toxicity , oversti- mulation of serotonin , and infant genotype.PNAS symptoms overlap those found in adult SSRI discontinuation syndrome, choliner- gic overdrive, and serotonin syndrome. The available evidence is conflicting.The overall data suggest that PNAS can occur in neonates exposed to SSRIs and SNRIs, yet have most often been reported after exposure to paroxetine, fluoxetine, and venlafaxine.

Persistent pulmonary hypertension of the newborn (PPHN):PPHN is a rare disorder that occurs in approximately 1–2 per 1000 births.Infants with PPHN present within twelve hours of birth with cyanosis and mild respiratory distress and can develop severe respiratory failure.Even with therapy, PPHN can be fatal in approximately 10–20% of cases.A recent population-based cohort study used national health register data demonstrated an increased risk of PPHN associated with SSRI prescription after 20-week gestation (Kieler H, ,2011). There are studies that have implicated other factors like caeserian section in PPHN.In December 2011, the FDA stated that there is insufficient evidence that antidepressant exposure during pregnancy causes PPHN.


Findings are inconsistent and difficult to interpret. Evidence is often limited.Many studies do not take into account confounding factors ( eg:whether reproductive outcomes are due to maternal illness or antidepressant exposure).

What to do?

1.Unless there is a reason to use another class of antidepressant, selective serotonin reuptake inhibitors are generally considered first-line in pregnancy.In new cases, many providers prefer fluoxetine .Strongly consider using an antidepressant that the woman has responded to in the past, to avoid unnecessary exposures during pregnancy. Use lowest effective dose. Avoid polypharmacy.Tapering antidepressants in the third trimester has not been shown the decrease in the incidence of postnatal adaptation syndrome or improve infant outcomes,and it carries the risk of precipitating relapse of depression.

2.Maximize non-medication evidence-based treatments.

3.Ensure individualised risk benefit analysis ,discussion and documentation.


Summary of the article:

Antidepressant use in pregnancy: a critical review focused on risks and controversies. Byatt N, Deligiannidis KM, Freeman MP. Acta Psychiatr Scand. 2013 Feb;127(2):94-114




One thought on “Risks of antidepressant use in pregnancy: Acta Psych Scand. March 2013.

  1. A decision to use antidepressants during pregnancy is based on the balance between risks and benefits. Overall, the risk of birth defects and other problems

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