Risk of neonatal extrapyramidal signs and/or withdrawal symptoms with antipsychotic drug use during third trimester of pregnancy

HSA would like to inform healthcare professionals that neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at potential risk of extrapyramidal signs (EPS) and/or withdrawal symptoms following delivery.

Antipsychotic drugs are used to treat symptoms of psychiatric disorders such as schizophrenia and bipolar disorders, and a list of the antipsychotic drugs registered in Singapore is shown in Table 1.

Table 1: Antipsychotic drugs registered in Singapore

Neonatal EPS or withdrawal

With the lack of large, well-designed, prospective comparative studies, there is currently limited information available on the safety of antipsychotic drugs in pregnancy. A search of the US Food and Drug Administration's (FDA) Adverse Event Reporting System database identified 69 suspected cases of neonatal EPS or withdrawal associated with antipsychotic drugs.¹

Symptoms reported include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorders, which may occur anytime from birth to one month after birth. The severity of the symptoms may vary, with some neonates recovering within hours or days without specific treatment, while others required intensive care support and prolonged hospitalisation.

It was not possible to determine if the events were a result of antipsychotic drug toxicity or withdrawal since blood levels of the implicated drugs were not provided. The majority of the cases were confounded by other factors, including concomitant use of other drugs known to be associated with withdrawal symptoms (such as antidepressants, benzodiazepines, non-benzodiazepine hypnotics and opioids), prematurity, congenital malformations, and obstetrical and perinatal complications (e.g., placental problems, pre-eclampsia). However, there were some suspected cases which suggest that neonatal EPS and withdrawal may occur with antipsychotic drugs alone.

Regulatory actions by the US FDA and Health Canada

In February 2011, the US FDA updated the “Pregnancy” section of package inserts for the entire class of antipsychotic drugs to provide consistent information about the above safety issue, and to remind healthcare professionals that antipsychotic drugs should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.¹

Similarly, in June 2011, Health Canada has also informed healthcare professionals and consumers that the prescribing information for antipsychotic drugs is being updated to reflect safety information on the potential risk of EPS or withdrawal in newborns whose mothers were treated with antipsychotic drugs during the third trimester of their pregnancy.²

Local situation and HSA's advisory

To date, HSA has not received any local reports of neonatal EPS or withdrawal associated with the use of antipsychotic drugs during the third trimester of pregnancy. Physicians are advised that the decision to use antipsychotic drugs should be made on a case-by-case basis, taking into consideration the woman's individual characteristics, her mental health history and tendency to relapse, the risk to the foetus, and the risk to both mother and foetus of not treating the disorder. Healthcare professionals are reminded to counsel patients about the benefits and risks of taking antipsychotic drugs during pregnancy, and to monitor neonates exhibiting EPS or withdrawal symptoms if they have been exposed to antipsychotic drugs in utero. Healthcare professionals are also strongly encouraged to report adverse events suspected to be related to antipsychotic drugs to the Vigilance Branch of HSA.

References

1. FDA Drug Safety Communication: Antipsychotic drug labels updated on use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns.http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm ↗ (opens in new tab)

2. Antipsychotic drugs: Labelling update regarding the risk of abnormal muscle movements and withdrawal symptoms in newborns exposed during pregnancy.
   http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2011/13616a-eng.php ↗ (opens in new tab)