Neonates exposed to antipsychotic medications during the third trimester of pregnancy may be at risk of experiencing extrapyramidal signs and/or withdrawal symptoms. Neonatal drug withdrawal symptoms may occur when drug exposure ceases at birth. All registered antipsychotics are now classified as Australian pregnancy category C.
The safety of antipsychotic use in pregnancy and lactation has not been thoroughly studied. The antenatal management of serious mental illnesses, such as schizophrenia and bipolar affective disorder, involves clinical decision-making about the continuation, commencement or discontinuation of psychotropic treatments. If the use of an antipsychotic in a pregnant woman is clinically indicated, avoid unnecessarily high doses and duration of treatment.6 The decision about using antipsychotics should be made on a case-by-case basis, taking into account the woman's individual characteristics, her mental health history and tendency to relapse, the risk to the fetus or infant, and the risk – to both mother and fetus – of not treating the disorder.7
The potential risks to the fetus or infant from antipsychotic exposure include structural teratogenicity, pregnancy complications (e.g. inducing maternal diabetes), effects on fetal growth, neonatal toxicity/withdrawal and long-term adverse neurodevelopmental outcomes. There is growing evidence that psychiatric disorders themselves appear to independently elevate the risk of spontaneous abortion, pre-eclampsia, premature birth, low birth weight, smaller head circumference and long-term adverse neurodevelopment.6,8
Reported cases
When used in pregnancy, many typical antipsychotics are known to be associated with the development of reversible extrapyramidal signs (EPS), such as dyskinetic movements, in the neonate. Although the incidence of EPS tends to be lower in patients treated with some atypical antipsychotics, this may not necessarily translate to a lower risk to neonates exposed in utero. Fetal exposure is largely dependent on placental transfer which can vary depending on the placental permeability of different antipsychotics. Spontaneous adverse event reporting provides evidence of both EPS and withdrawal symptoms occurring in the neonate following chronicin uteroexposure to atypical antipsychotics.
To May 2011, the TGA had received 19 reports of EPS or withdrawal symptoms in neonates. Of these, an atypical antipsychotic was suspected in 18 reports. Many reported cases were confounded by concomitant use of other psychotropic medication (e.g. antidepressants), obstetric complications (e.g. fetal distress) or tobacco and alcohol exposure. However an antipsychotic alone was suspected in four reports.
In the cases reported to the TGA, adverse events included jitteriness, agitation, tremor, feeding problems, somnolence, breathing difficulties, hypertonia, hypotonia, pronounced startle reflex and myoclonus. Although the term 'neonatal drug withdrawal' was specifically identified in 14 reports, it was not possible to definitively determine whether these were related directly to antipsychotic toxicity or to withdrawal. Reported time to onset ranged from birth to seven days. Where outcome was described, most neonates recovered within a few days although some required supportive therapy and prolonged hospitalisation. An analysis of adverse events reported in the United States described similar findings.9
Changes to PI for antipsychotics
PI documents for all antipsychotics are being updated with warnings about neonatal EPS and withdrawal symptoms. All registered antipsychotics are Australian pregnancy category C. Category C refers to: 'Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.'
See below for information about the TGA's new 'Prescribing medicines in pregnancy' database.