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Antidepressant exposure increases risk for birth defects

Findings from a population-wide cohort study indicated exposure to antidepressants with serotonin reuptake effects during embryogenesis increased risk for organ-specific malformations.

“Serotonin is essential for healthy fetal development during embryogenesis. Selective serotonin reuptake inhibitors cross the placental barrier and bloc serotonin reuptake transporter sites, disturbing the free movement of serotonin during this critical phase of development,” Anick Bérard, PhD, of Centre Hospitalier Universitaire Sainte-Justine, Montreal, and colleagues wrote. “Human studies concerning the adverse effects of antidepressant exposure during gestation on the developing fetus have showed increased risk of various congenital malformations, such as cardiac, musculoskeletal, respiratory, craniosynostosis and craniofacial, but variations between study results remain.”

To determine associations between first-trimester exposure to antidepressants and risk for congenital malformations, researchers analyzed data from the Quebec Pregnancy Cohort for 18,487 women with depression or anxiety exposed to antidepressants within 12 months before pregnancy.

Analysis of specific antidepressant types indicated only citalopram increased risk for major congenital malformations (adjusted OR = 1.36; 95% CI, 1.08-1.78). However, researchers noted a trend toward increased risk for most frequently used antidepressants.

Antidepressants with serotonin reuptake inhibition effect increased risk for organ-specific defects.

Paroxetine increased risk for cardiac defects (aOR = 1.45; 95% CI, 1.12-1.88) and ventricular/atrial septal defects (aOR = 1.39; 95% CI, 1-1.93).

Citalopram increased risk for musculoskeletal defects (aOR = 1.92; 95% CI, 1.4-7.52) and craniosynostosis (aOR = 3.95; 95% CI, 2.08-7.52).

Tricyclic antidepressants increased risk for eye, ear, face and neck defects (aOR = 2.45; 95% CI, 1.05-5.72) and digestive defects (aOR = 2.55; 95% CI, 1.4-4.66).

Venlafaxine was associated with increased risk for respiratory defects (aOR = 2.17; 95% CI, 1.07-4.38).

“We found that infants were at an increased risk of cardiac, musculoskeletal, craniofacial, digestive and respiratory defects, as well as craniosynostosis from in utero exposure to serotonin inhibitor drugs (SSRI, [serotonin-norepinephrine reuptake inhibitors] and some [tricyclic antidepressants]),” the researchers wrote. “Given that an increasing number of women are diagnosed with depression during pregnancy, these results have direct implications on their clinical management. This is even more important given that the effectiveness of antidepressants during pregnancy for the treatment of the majority of cases of depression (mild to moderate depression) have been shown to be marginal. Hence, the need for caution with antidepressant use during pregnancy is warranted and alternative non-drug options should be considered.” – by Amanda Oldt

Disclosure: Bérard reports serving as a consultant for plaintiffs in litigations involving antidepressants and birth defects. Please see the study for a full list of all other researchers’ relevant financial disclosures.