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. Olanzapine is an atypical antipsychotic agent belonging to the thienobenzodiazepine group chemically and is similar to clozapine both chemically and in its mechanism of action. It is known to cross the placenta.[135] Animal reproductive studies in rats and rabbits have revealed no evidence of teratogenic effects at doses higher than the human recommended dose but have shown increased resorption, increased number of nonviable fetuses, and decreased fetal weight.

In humans. Schenker et al[195] described a study in which it was observed that 5% to 14% of olanzapine crosses human placenta unchanged during a period of 4 hours. Goldstein et al[196] described 23 prospectively and 9 retrospectively ascertained pregnancy reports that were collected as a registry in the Lilly Worldwide Pharmacovigilance Safety Database. Outcomes from the 23 prospective reports were as follows: spontaneous abortion in 3 (13%); stillbirth in 1 (5%) after premature rupture of membranes at 37 weeks' gestation in a mother with gestational diabetes, thrombocytopenia, hepatitis, and polydrug abuse; normal birth in 16 (80%); prematurity in 1 (5%) delivered by cesarean section at 30 weeks because of gestational diabetes, hypothyroidism, preeclampsia, and abnormal liver enzymes in a mother taking insulin, levothyroxine, famotidine, and folic acid; and postmaturity in 2, one delivered by induction 10 days after term because of fetal distress and another who had meconium aspiration after delivery by cesarean section because of postmaturity. These are all within the range of normal historic control rates -- ie, these pregnancies did not have an increased risk of spontaneous abortion, stillbirth, prematurity, or major malformation in the offspring.

Among the 9 retrospective reports described by Goldstein et al,[196] there were 2 spontaneous abortions; 1 normal infant; 2 major malformations -- Down syndrome (trisomy 21), caused by chromosomal nondysjunction (a defect not considered to be due to a teratogen) and unilateral renal dysplasia unlikely to be related to teratogenicity because a chemical insult would typically be bilateral; 1 therapeutic abortion done at the patient's request; 1 perinatal complication that resulted in neonatal withdrawal because of decreased plasma concentration; 2 postperinatal complications -- convulsions in one (despite normal findings on electroencephalogram and laboratory tests) and sudden infant death syndrome in one. Absence of similar events in prospectively identified cases suggests the lack of causation.[196] Therefore, olanzapine should be used in potentially childbearing women, unless, in the opinion of the physician, the potential risk to the fetus or infant outweighs the expected benefit to the patient.

Risk to Infant During Breast-Feeding

Evidence suggests that olanzapine is excreted in rat milk, but its excretion in human breast milk has not been studied.[196] Goldstein et al[196] described two retrospectively identified case reports of lactation exposures. In the first case, a mother with paranoid schizophrenia was taking 10 mg of olanzapine along with trifluoperazine, procyclindine, and paroxetine when her infant was 2 months of age. No adverse effects were noticed in this breast-fed infant. The second report described jaundice, somnolence, cardiomegaly, and heart murmur in a breast-fed infant whose mother had taken 5 mg of olanzapine daily in the first and third trimesters. The infant's birth weight was 3.8 kg, birth length was 50 cm, and Apgar scores were 8 and 9 at 1 minute and 5 minutes, respectively. The infant had been healthy and fully breast-fed until day 6. On day 7, bottle feeding was initiated, but jaundice and sedation continued, suggesting a lack of relationship to olanzapine. Conclusions cannot be based on only two cases. Hence, until olanzapine in human breast milk is studied more throughly, it should be assumed to be readily present, and women should be advised not to breast-feed their infant.


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