Risk Factor: C
Class: Central nervous system drugs/ Tranquilizers

Contents of this page:
Fetal Risk Summary
Breast Feeding Summary

Fetal Risk Summary

Chlorpromazine is a propylamino phenothiazine. The drug readily crosses the placenta (1,2,3 and 4). Reproductive studies in rodents have shown a potential for embryotoxicity, increased neonatal mortality, and decreased offspring performance (5). In animals, selective accumulation and retention occur in the fetal pigment epithelium (6). Although delayed ocular damage from high prolonged doses in pregnancy has not been reported in humans, concern has been expressed for this potential toxicity (6,7).

Chlorpromazine has been used for the treatment of nausea and vomiting of pregnancy during all stages of gestation, including labor, since the mid-1950s (8,9 and 10). The drug seems to be safe and effective for this indication. Its use in labor to promote analgesia and amnesia is usually safe, but some patients, up to 18% in one series, have a marked unpredictable fall in blood pressure that could be dangerous to the mother and the fetus (11,12,13,14 and 15). Use of chlorpromazine during labor should be discouraged because of this adverse effect.

One psychiatric patient, who consumed 8000 mg of chlorpromazine in the last 10 days of pregnancy, delivered a hypotonic, lethargic infant with depressed reflexes and jaundice (4). The adverse effects resolved within 3 weeks.

An extrapyramidal syndrome, which may persist for months, has been observed in some infants whose mothers received chlorpromazine near term (16,17,18,19 and 20). This reaction is characterized by tremors, increased muscle tone with spasticity, and hyperactive deep tendon reflexes. Hypotonicity has been observed in one newborn and paralytic ileus in two after exposure at term to chlorpromazine (4,21). However, most reports describing the use of chlorpromazine in pregnancy have concluded that it does not adversely affect the fetus or newborn (22,23,24,25,26 and 27).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 142 of whom had 1st trimester exposure to chlorpromazine (28). For use anytime during pregnancy, 284 exposures were recorded. No evidence was found in either group to suggest a relationship to malformations or an effect on perinatal mortality rate, birth weight, or intelligence quotient scores at 4 years of age. Opposite results were found in a prospective French study that compared 315 mothers exposed to phenothiazines during the 1st trimester with 11,099 nonexposed controls (29). Malformations were observed in 11 exposed infants (3.5%) and in 178 controls (1.6%) (p
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 36 newborns had been exposed to chlorpromazine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). No major birth defects were observed (two expected).

In an in vitro study, chlorpromazine was shown to be a potent inhibitor of sperm motility (31). A concentration of 53 mmol/L produced a 50% reduction in motility.

Using data from the CPP, researchers discovered that offspring of psychotic/neurotic mothers who had consumed chlorpromazine or other neuroleptics for more than 2 months during gestation, whether or not they were breast fed, were significantly taller than nonexposed controls at 4 months, 1 year, and 7 years of age (32). At 7 years of age, the difference between the exposed and nonexposed groups was approximately 3 cm. The mechanisms behind these effects were not clear, but may have been related to the dopamine receptor-blocking action of the drugs.

In summary, although one survey found an increased incidence of defects and a report of ectromelia exists, most studies have found chlorpromazine to be safe for both mother and fetus if used occasionally in low doses. Other reviewers have also concluded that the phenothiazines are not teratogenic (26, 33). Another review concluded that because of its extensive clinical experience, chlorpromazine should be included among the treatments of choice if antipsychotic therapy was required during pregnancy (34). However, use near term should be avoided due to the danger of maternal hypotension and adverse effects in the newborn.

Breast Feeding Summary

Chlorpromazine is excreted into breast milk in very small concentrations. Following a 1200 mg oral dose (20 mg/kg), peak milk levels of 0.29 mg/mL were measured at 2 hours (35). This represented a milk:plasma ratio of less than 0.5. The drug could not be detected following a 600 mg oral dose. In a study of four lactating mothers consuming unspecified amounts of the neuroleptic, milk concentrations of chlorpromazine ranged from 798 ng/mL with maternal serum levels ranging from 1652 ng/mL (36). In two mothers, more of the drug was found in the milk than in the plasma. Only two of the mothers breast-fed their infants. One infant, consuming milk with a level of 7 ng/mL, showed no ill effects, but the second took milk containing 92 ng/mL and became drowsy and lethargic.

With the one exception described above, there has been a lack of reported adverse effects in breast-fed babies whose mothers were ingesting chlorpromazine (26). Based on this report, however, nursing infants exposed to the agent in milk should be observed for sedation. The American Academy of Pediatrics classifies chlorpromazine as an agent whose effect on the nursing infant is unknown but may be of concern because of the drowsiness and lethargy observed in the infant described above, and because of the galactorrhea induced in adults (37).



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