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

Chlorpromazine

Risk to Fetus

In animals. Chlorpromazine is a derivative of aliphatic phenothiazines, and it readily crosses the placenta.[144,145] Animal reproductive studies in rodents and monkeys have shown that doses higher than those recommended in humans cause teratogenic effects such as cleft palate and anomalies of the central nervous system, eye, and skeletal system.[146,147,148] Also reported are fetotoxic effects such as fetal death, decreased fertility and viability, and decreased fetal weight gain,[146,147,148] visual disturbances,[149] and behavioral abnormalities,[150,151] but not embryotoxic effects.

In humans. Adequate and well-controlled epidemiologic studies to determine the teratogenic potential of chlorpromazine have not been done in pregnant women. Many clinical studies have shown the safety and efficacy of low-dose chlorpromazine when used either to treat nausea and vomiting during all stages of gestation[152,153] or to promote analgesia, amnesia, and sedation during labor.[154,155,156] However, there are isolated instances of marked idiosyncratic falls in blood pressure, which could be dangerous to the mother and the fetus.[153,157]

Sobel[158] observed that among 52 women who were given chlorpromazine during late pregnancy, 3 women receiving high doses (500 to 600 mg daily) gave birth to neonates with respiratory distress and cyanosis. Also, neurologic dysfunction with extrapyramidal signs (ie, muscle rigidity, hypertonia, tremor, dyskinesias, akathisia, weakness, poor sucking, and poor motor maturity) has been reported in several infants born to women who were treated with chlorpromazine during late pregnancy, suggesting a withdrawal syndrome.[144,159,160,161] The frequency of these complications appears to be low, and they are usually transient, though some may last for several months.[162]

Levin et al[163] observed that irrespective of their breast-feeding status, the children of mothers who took chlorpromazine or other neuroleptics for more than 2 months during gestation were significantly taller than unexposed controls at 4 months, 1 year, and 7 years of age.

Sobel[164] reported higher incidences of perinatal mortality and morbidity in neonates born to schizophrenic mothers in a mental hospital, irrespective of their chlorpromazine status. He attributed these adverse effects to the schizophrenia. Similar findings were observed by Reider et al.[165] In one study involving 142 neonates, in utero exposure to chlorpromazine during the first 4 months of pregnancy did not result in a significantly higher risk of congenital anomalies.[166] Similar results were found in neonates of 284 women treated with chlorpromazine during pregnancy.[167] Contrasting results were observed in a prospective study of 12,764 women; a higher number of birth defects occurred in neonates of 189 women receiving phenothiazines, especially chlorpromazine, during the last trimester.[168]

In summary, most studies agree that chlorpromazine is safe during gestation and that it is not teratogenic,[155,169] despite isolated reports describing congenital anomalies. However, it is prudent to avoid this drug near term, if possible, since it has been reported to cause maternal hypotension with adverse effects in neonates.

Risk to Infant During Breast-Feeding

Chlorpromazine is excreted in the breast milk of nursing mothers in low concentrations up to 3% of maternal daily dosage per kilogram of body weight.[170,171] On a regimen of 600 mg twice daily for 7 days, the drug was not detected in the morning milk samples. Another study found no adverse effects in 6 neonates nursed by mothers taking chlorpromazine, of whom 4 were nursed for 3 months, 1 for 7 weeks, and 1 for 1 month. All the mothers had nursed at least one other child previously and reported no difficulties in the infants nursed while they were taking chlorpromazine.[172]

Estimations based on data collected from five lactating women taking the drug showed that the nursing infant would be expected to ingest between 0.03% and 1.3% of the lowest pediatric dose.[173,174] Thus, chlorpromazine can be used safely in nursing women.

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