Prescribing SGAs During Pregnancy Flavio Guzmán, MD

Overview Risks of congenital malformations Risks of neonatal effects and developmental abnormalities Treatment recommendations: monitoring

Teratogenicity risks

Risk of congenital malformations Relative comfort in prescribing APs Absence of negative data Studies haven’t described major congenital malformations associated with SGAs Snellen, M., & Malhi, G. S. (2014). Bipolar Disorder, Psychopharmacology, and Pregnancy. In Psychopharmacology and Pregnancy (pp. 103-117). Springer Berlin

Risk of congenital malformations National Pregnancy Registry for Atypical Antipsychotics Cohen, L. S., et al (2015). Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. American Journal of Psychiatry, 173(3), 263-270.

Risk of congenital malformations Primary aim: quantify the risk for congenital malformations Modeled after North American AED Registry Based in the Massachusetts General Hospital, Boston National Pregnancy Registry for Atypical Antipsychotics Cohen, L. S., et al (2015). Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. American Journal of Psychiatry, 173(3), 263-270.

Risk of congenital malformations No substantial increase in risk of major malformations Use of a SGA during first trimester National Pregnancy Registry for Atypical Antipsychotics Cohen, L. S., et al (2015). Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. American Journal of Psychiatry, 173(3), 263-270.

Risk of congenital malformations SGA Substantial morbidity Maintain current AP National Pregnancy Registry for Atypical Antipsychotics Good response to SGA Cohen, L. S., et al (2015). Reproductive safety of second-generation antipsychotics: current data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics. American Journal of Psychiatry, 173(3), 263-270.

Neonatal effects

Neonatal effects FDA labeling (changed in 2011) Extrapyramidal signs “Withdrawal symptoms” Sedation Agitation Changes in muscle tone Breathing and feeding difficulties FDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm#aihp

Maternal weight and neonatal effects Effect on maternal weight SGAs may increase maternal weight Population based cohort study Increased risk of gestational diabetes Bodén, R., Lundgren, M., Brandt, L., Reutfors, J., & Kieler, H. (2012). Antipsychotics during pregnancy: relation to fetal and maternal metabolic effects. Archives of general psychiatry, 69(7), 715-721.

Maternal weight and neonatal effects Higher incidence of large-for-gestational-age deliveries SGAs: 20% FGAs: 2% Other reports: higher weight with antenatal olanzapine exposure Large for Gestational Age (LGA) Newham, J. J.et al (2008). Birth weight of infants after maternal exposure to typical and atypical antipsychotics: prospective comparison study. The British Journal of Psychiatry, 192(5), 333-337. Babu, G. N., et al (2010). Birth weight and use of olanzapine in pregnancy: a prospective comparative study. Journal of clinical psychopharmacology, 30(3), 331-332.

Neurodevelopmental effects

Neurodevelopmental effects Developmental delays Present at 6 months At 12 months there were no differences Women in the exposed group were: More likely to be overweight Less likely to take vitamins Peng, M., Gao, K. et al (2013). Effects of prenatal exposure to atypical antipsychotics on postnatal development and growth of infants: a case-controlled, prospective study. Psychopharmacology, 228(4), 577-584.

Recommendations

Recommendations Ultrasound of fetal size in late pregnancy Monitor glucose levels Chisolm, M. S., & Payne, J. L. (2016). Management of psychotropic drugs during pregnancy. BMJ, 352, h5918.

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