Depression in Pregnancy: Treat or Do Not Treat?

Globally, mental health disorders are increasingly prevalent worldwide with depression particularly contributed to the largest percentage of global disability (7.5% of all years lived with disability in 2015). It is more common in females than males affecting 4 -7% of women in reproductive age group [1]. Women with mild depression are treated with cognitive based therapy and antidepressants are used depending on the severity of the symptoms [2]. Utilizing antidepressants preconception and during pregnancy was assessed in wide range of studies to evaluate the risk of associated congenital anomalies. Ornoy et al reviewed the association between tricyclic antidepressants (TCA) and congenital anomalies. Early studies showed slight increase in the associated risk however the following large studies showed no association [2]. An updated analysis of the Quebec cohort of 18487 depressed pregnant women revealed increased risk of major congenital anomalies with citalopram (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases) mainly anomalies related musculoskeletal system and craniosynostosis. In general, TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66) [3]. New generation antidepressants such as selective serotonin reuptake inhibitors (SSRI) and selective norepinephrine reuptake inhibitors (SNRI) were also evaluated. A systematic review of 23 studies evaluated the associated risk of congenital anomalies with Paroxetine (SSRI) in first trimester versus no exposure. Paroxetine was associated with 23% increased risk of any major congenital anomaly in meta-analysis of 15 studies. Cardiac anomalies were significantly increased mainly bulbus cordis anomalies and anomalies of cardiac septal closure (pooled OR 1.42, 95% CI 1.07, 1.89; n = 8 studies), atrial septal defects (pooled OR 2.38, 95% CI 1.14, 4.97; n =4 studies) and right ventricular outflow track defect (pooled OR 2.29, 95% CI 1.06, 4.93; n =4 studies) [4]. In a systematic review of 12 cohort studies, first trimester exposure to Sertraline (SSRI) was significantly associated with cardiac anomalies (OR =1.36; 95% CI =1.06-1.7) specifically atrial and ventricular septal defects [5]. A third systematic review of eight studies showed no increased risk of congenital anomalies with first trimester exposure to either Venlafaxine or Duloxetine knowing that included sample size was small in this review [6]. A population-based case-control study involving 3.3 million births from 12 European registries showed that first trimester uses of selective serotonin reuptake inhibitor (SSRI) is associated with congenital heart diseases mainly Tetralogy of Fallot (OR 3.36, 95 % CI 1.67-6.75), and Ebstein’s anomaly (OR 8.23, 95 % CI 2.91-23.28) [7]. Another analysis of three populationbased registries of 519, 117 deliveries showed that preconception or early exposure to SSRI is associated with congenital heart diseases however stopping these medications prior to pregnancy reduces the risk of subsequent anomalies [8]. SSRI type was not identified in both population-based analyses.