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. Fluphenazine belongs to the piperazine phenothiazine group and readily crosses the placenta and accumulates in fetal tissue.[183] Two studies in which rats were treated with doses up to 100 mg/kg orally throughout pregnancy found no adverse effects in the offspring.[184] Contradictory results were reported in pregnant mice given this drug, with a significantly higher incidence of skeletal defects, dilated ventricles, and reduction in fetal weight and length.[185] Multiple malformations in chick embryos and cleft palate in fetal mice have been reported in experimental studies involving fluphenazine.[175]

In humans. No adequate, well-controlled studies have determined the teratogenicity of fluphenazine. However, a retrospective study[186] involving 244 patients taking fluphenazine and 150 controls, detected congenital anomalies in 2.7% of the 226 live and stillborn infants in the exposed group compared with 3.5% among 143 live and stillborn deliveries in the control group. Also, the incidences of spontaneous abortion, perinatal mortality, premature birth, and twinning in the two groups were similar.

Currently available clinical data have not shown any teratogenic effects, except for occasional case reports of congenital anomalies,[187,188] and a case of rhinorrhoea and respiratory distress,[183] in which causality could not been established. The bulk of the worldwide clinical experience with this drug indicates that pregnant women can be treated with fluphenazine without any ill effects on them or their infants.[189] However, a clinician should weigh the potential risks to the fetus against the probable benefits to the mother when administering this drug to a pregnant patient.

Risk to Infant During Breast-Feeding

Even though fluphenazine, like other phenothiazines, may be excreted into breast milk, neither the drug nor its metabolites have been quantified in human milk, and its effect on nursing infants is unknown. Therefore, it may be administered during nursing if a risk-benefit assessment justifies a possible risk to the infant, and the infant should be observed for development of any adverse effects.


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