Effects of Antimanic Mood-Stabilizing Drugs on Fetuses, Neonates, and Nursing Infants

Mohammad Masud Iqbal, MD, MPH, MSPH, DTM; Sai Prakash Gundlapalli, MD, William G. Ryan, MD, Thad Ryals, MD, Birmingham, Ala; Terry E. Passman, MD, Department of Psychiatry and Behavioral Neurobiology, the Regional Neonatal Intensive Care Unit, and the Department of Epidemiology and International Health, University of Alabama at Birmingham School of Medicine; and the Harbor Unit, Thomas Hospital, Fairhope, Ala

South Med J. 2001;94(3) 

In This Article


Risk to Fetus

In animals. Clozapine, a dibenzodiazepine derivative, is an atypical antipsychotic that readily crosses the placenta.[190] Animal reproductive studies in rats and rabbits have shown no teratogenic, fetotoxic, or embryotoxic effect at doses approximately 2 to 4 times the human dose.[135]

In humans. Presently, no epidemiologic studies show an association between congenital anomalies and gestational clozapine therapy. There are three clinical case reports of no apparent fetal adverse effects associated with the use of clozapine before and during gestation.[192,193,194] One of these reports described 14 women who were known to have been exposed to clozapine during gestation with no known adverse sequelae in their newborns.[194] White blood cell counts of all newborn infants of mothers receiving clozapine during pregnancy or while nursing should be monitored carefully to detect agranulocytosis or bone marrow suppression that could result in a life-threatening infection. It has been shown that agranulocytosis develops in the first 6 months of treatment either precipously or gradually and one third of the patients who had agranulocytosis from clozapine died. Clozapine can be used during pregnancy if the clinical benefit to the mother justifies the possible risk to the fetus.

Risk to Infant During Breast-Feeding

Clozapine is concentrated into breast milk[135,190,192] and has been known to cause sedation, decreased suckling, restlessness or irritability, seizures, and cardiovascular instability in the nursing infant.[190] Given this potential for serious adverse consequences to infants who are exposed to clozapine, breast-feeding should be avoided during maternal clozapine therapy.


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