Antipsychotic
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
The human pregnancy experience with pimozide is limited, but no embryo–fetal harm has been reported. The animal data do not suggest a risk of teratogenicity, but the lack of a meaningful comparison with the human dose limits the data’s usefulness. The use of antipsychotics, including pimozide, close to delivery may cause extrapyramidal effects (Parkinson-like symptoms; akinesia) in the newborn (1). Until adequate human pregnancy experience has been reported, the safest course is to avoid pimozide in pregnancy, especially in the 1st trimester and close to delivery. However, it should not be withheld because of pregnancy if it is the best drug for the patient.
FETAL RISK SUMMARY
Pimozide is an orally active antipsychotic agent that blocks dopaminergic receptors on neurons in the CNS. It is indicated for the suppression of motor and phonic tics in patients with Tourette’s syndrome who have failed to respond satisfactorily to standard treatment. Pimozide is extensively metabolized, primarily in the liver, but the antipsychotic activity of the metabolites has not been determined. In schizophrenic patients, the mean serum elimination half-life was about 55 hours (2).
Reproduction studies have been conducted in rats and rabbits. In rats, oral doses up to 8 times the maximum human dose (HD) were not teratogenic, but decreased rates of pregnancies and increased rates of retarded fetal development were observed. The decreased pregnancy rates were thought to be due to an inhibition or delay in implantation, an effect in rodents that has been observed with other antipsychotic drugs. Although rat fertility studies were not adequate to assess all aspects of fertility, pimozide caused prolonged estrus cycles similar to those observed with other antipsychotics. In the rabbit, dose-related (doses not specified) maternal toxicity, mortality, decreased weight gain, and embryo toxicity, including increased resorptions, were noted (2).
Dose-related increases in pituitary and mammary gland tumors in female mice were observed in long-term studies. The latter tumors may have been related to drug-induced elevated prolactin levels. Doses up to 50 times the HD were not tumorigenic in rats, but the limited number of animals surviving this study makes the findings unclear (2).
It is not known if pimozide crosses the human placenta. The molecular weight (about 462) and prolonged elimination half-life suggest that the drug will cross to the embryo–fetus.
A 2006 case report described the use of pimozide throughout pregnancy (3). The 26-year-old woman had been diagnosed with Tourette’s syndrome at the age of 12–13 years and was treated with pimozide 1–3 mg/day. At age 19 years, in addition to the occurrence of tics from Tourette’s syndrome, she began to experience symptoms of obsessive-compulsive disorder (OCD). Fluoxetine 20 mg daily partially controlled the new disorder. Pimozide 1 mg/day (the usual maintenance dose is 2–6 mg/day) and fluoxetine were continued until the 27th week of pregnancy at which time she discontinued fluoxetine. Ultrasound examinations of the fetus conducted 7 times from weeks 8 through 27 were normal. A cesarean section was planned for week 38 and, to prevent potential toxicity in the newborn, pimozide was discontinued at 36 weeks’ gestation. However, 1 week after stopping pimozide the patient developed continuous, severe tics with drastic movements and grimaces always followed by coughing tics. In addition, she experienced intense symptoms of OCD and pulled out her hair. During this period, the woman took several doses of oxazepam. Because of the severity of the combined symptoms, an emergency cesarean section was performed to deliver a healthy, 2448-g male infant with Apgar scores of 7, 8, and 10 at 1, 5, and 10 minutes, respectively. Results of physical and neurologic examinations of the infant at delivery and on day 3 of life were normal. On day 3, an electroencephalogram was obtained, and although the infant was asleep during most of the examination, no abnormalities were observed. The mother restarted pimozide after delivery and decided not to breastfeed (3).
In a brief 2009 report, a 29-year-old woman with Tourette’s syndrome was treated with pimozide 4 mg/day throughout gestation (4). She gave birth to a healthy female infant (no other data available).
BREASTFEEDING SUMMARY
No reports describing the use of pimozide during human lactation have been located. The molecular weight (about 462) and prolong elimination half-life (about 55 hours) suggest that the drug will be excreted into breast milk. The effects, including effects on neurodevelopment, of this exposure on a nursing infant are unknown. If a woman taking this drug decides to breastfeed, her infant should be closely monitored for adverse effects seen in adults, such as extrapyramidal reactions (Parkinson-like symptoms; akinesia), sedation, and constipation.
References
1.Committee on Drugs. American Academy of Pediatrics. Use of psychoactive medication during pregnancy and possible effects on the fetus and newborn. Pediatrics 2000;105:880–7.
2.Product information. Orap. Gate Pharmaceuticals, 2004.
3.Bjarnason NH, Rode L, Dalhoff K. Fetal exposure to pimozide: a case report. J Reprod Med 2006;51:443–4.
4.Prowler ML, Kim DR. Perinatal akathisia: implications for pharmacokinetic changes during pregnancy. Am J Psychiatry 2009;166:1296–7.