Antidepressant use during early pregnancy and the risk of congenital anomalies

Pharmacotherapy. 2013 Jul;33(7):693-700. doi: 10.1002/phar.1211. Epub 2013 Jun 6.


Study objective: To estimate and compare the prevalence of congenital anomalies among the offspring of women exposed and not exposed to antidepressants during early pregnancy.

Design: Matched cohort study.

Data source: United Kingdom's General Practice Research Database.

Subjects: Women exposed to tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants during the first trimester of pregnancy (3276 women) and a sample of women matched in a 2:1 ratio who had no exposure to any antidepressant during the first trimester of pregnancy (6617 women).

Measurements and main results: The prevalence of any congenital anomaly was 31.0 (95% confidence interval [CI] 27.0-35.5) per 1000 pregnancies among women not exposed to antidepressants and 27.2 (95% CI 22.1-33.4) per 1000 pregnancies among women exposed to antidepressants. The relative risk of having a child with an anomaly in mothers who were exposed to tricyclics and SSRIs during the first trimester compared with mothers not exposed to these drugs was 0.9 (95% CI 0.7-1.1). The relative risks for any anomaly among women exposed to antidepressants were 0.9 (95% CI 0.6-1.2) for tricylics and 0.9 (95% CI 0.7-1.2) for SSRIs. We found no statistically significant, stable increases in the risk of specific anomaly subtypes among women exposed to these antidepressants; however, the number of exposed cases was small.

Conclusion: Exposure to tricyclics and SSRIs during the first trimester of pregnancy was not associated with a statistically significant increased risk of congenital anomalies in the offspring of mothers exposed to these drugs.

Keywords: antidepressants; congenital anomalies; prevalence rates; relative risk.

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / adverse effects*
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Cohort Studies
  • Congenital Abnormalities / epidemiology*
  • Congenital Abnormalities / etiology
  • Databases, Factual
  • Depression / complications
  • Depression / drug therapy*
  • Female
  • Humans
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Trimester, First
  • Prevalence
  • Risk
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / adverse effects*
  • Serotonin Uptake Inhibitors / therapeutic use
  • United Kingdom
  • Young Adult


  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors