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2. Reviewing the Literature: Teratogenicity
Vivien Burt, PhD, MD
The Women’s Life Center Resnick Neuropsychiatric Hospital at UCLA

3. Finnish Case-Control Study
600, mother-child pairs
Recorded first-time SSRI purchases
Women who purchased SSRIs were:
Less likely to be married
More likely to:
Smoke
Have chronic diseases
Use non-SSRI psychotropics
Use nonpsychotropics
Malm, H., Artama, M., Gissler, M., & Ritvanen, A. (2011). Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & gynecology, 118(1),

4. Study Results
No significant increase in risk for overall major malformations
Risk for ventricular septal defect (VSD)
Fluoxetine
X 2
SSRIs
Risk for right ventricular outflow tract defects (RVOT)
Risk for neural tract defects
Paroxetine
Citalopram
X 5
X 2.5
Malm, H., Artama, M., Gissler, M., & Ritvanen, A. (2011). Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & gynecology, 118(1),

5. Risk of Fetal Alcohol Spectrum Disorders
Underlying psychiatric
conditions responsible for
SSRI and alcohol use
X 10 times
in SSRI-exposed cases
Confounding by indication
Depression may predispose to adverse outcomes
Malm, H., Artama, M., Gissler, M., & Ritvanen, A. (2011). Selective serotonin reuptake inhibitors and risk for major congenital anomalies. Obstetrics & gynecology, 118(1),

6. Current study design Ideal study design SSRI-exposed Unexposed
Placebo Vs Vs
Depressed women
Nondepressed women
Depressed women
Depressed women
Unethical

7. A million members of a Medicaid population
Study Results
A million members of a Medicaid population
Primary outcome
Secondary outcome
Major cardiac malformations (MCMs)
Ventricular flow obstruction
Ventricular septal defects
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., ... & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370(25),

8. Population-Based Cohort Study
Methodology
Propensity matching
Address the severity of maternal depression
Using “proxies”
Pain-related disorders
Suggest severe
depression
Sleep disorders
Smoking
Chronic fatigue syndrome
Exposure
Pharmacy records of drugs supplied in the first trimester
Recorded
Cardiac malformations in maternal-infant records
First 90 days postpartum
Maternal depression diagnosis
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., ... & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370(25),

9. Adjusted for depression and equivalent markers
Conclusion
Adjusted for depression and equivalent markers
Unadjusted
data
Risk for overall cardiac defects with:
No statistically significant risk of cardiac malformation with first trimester exposure to:
Any antidepressant
SSRIs
SNRIs
Bupropion
SSRIs as a group
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., ... & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370(25),

10. Conclusion
No significant association between SSRIs as a group and overall cardiac defects
No significant association between paroxetine and right ventricular outflow tract obstruction
SSRIs
No significant association between sertraline and ventricular septal defects
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., ... & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370(25),

11. SSRI Antidepressants and Risk for Teratogenicity
SSRIs are the most studied antidepressants in pregnancy.
SSRI use is not associated with specific morphologic teratogenic risks.
# 1 cardiac defects
The background risk for major congenital malformations is 3%. 3%
Most are self-correcting over the months of early infancy.
VSD
Alwan, S., Reefhuis, J., Rasmussen, S. A., Olney, R. S., & Friedman, J. M. (2007). Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New England Journal of Medicine, 356(26),
Louik, C., Lin, A. E., Werler, M. M., Hernández-Díaz, S., & Mitchell, A. A. (2007). First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. New England Journal of Medicine, 356(26),
Greene, M. F. (2007). Teratogenicity of SSRIs—serious concern or much ado about little?.
Wisner, K. L., Sit, D. K., Hanusa, B. H., Moses-Kolko, E. L., Bogen, D. L., Hunker, D. F., ... & Singer, L. T. (2009). Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Focus, 7(3),
Stewart, D. E. (2012). Clinical Practice: Depression During Pregnancy. Obstetric Anesthesia Digest, 32(4),

12. Key Points
Overall, SSRI use has not been associated with specific morphologic teratogenic risks.
Maternal stress and depression during pregnancy are associated with serious maternal illness, poor health behaviors, and an increased risk for postpartum illness.
Discontinuation of antidepressants in pregnancy is associated with a relapse of depression and incurs negative consequences for the mother, baby, and family.

13. Next Presentation Antidepressant Impact on Neonatal and Long-Term Outcomes