One-Year Mother & Baby Outcomes Following Antipsychotic Use in Pregnancy

Jayashri Kulkarni, MBBS, MPM, FRANZCP, PhD
Director, Monash Alfred Psychiatry Research Centre, Melbourne, Australia

Disclosure: This research received grant support from Astra Zeneca, Janssen Cilag, Hospira, and Rotary Australia (no commercial company had any input in the study design, data gathering, manuscript preparation, or any editorial input at all); Dr. Kulkarni has received speaker fees from Astra Zeneca, Janssen Cilag, Lundbeck, Lilly, and Roche; and has served on the advisory boards of Astra Zeneca, Janssen Cilag, Lundbeck, Lilly, and Roche.


This article was originally published in Psychiatry Weekly, on June 23, 2014.


Women of childbearing age form one of the most highly represented cohorts among people with a current psychiatric disorder. This apparent greater vulnerability to mental illness in women is so well documented as to be nearly axiomatic. Yet there is a highly disproportionate lack of evidence on managing more severe mental illnesses, such as bipolar disorder or psychotic disorders, during pregnancy and the antenatal period. There is especially little evidence on the safety of atypical antipsychotics during pregnancy. Such data are critically needed as new indications, and growing off-label use of these drugs to manage other mood and anxiety disorders, continue to expand.

This lack of evidence came into sharp relief for Dr. Jayashri Kulkarni after a colleague’s patient, a woman with schizophrenia, became permanently destabilized after stopping antipsychotic therapy in pregnancy. The case eventually ended in tragedy and led Dr. Kulkarni on a search for evidence to see “where it had all gone wrong for this particular patient.”

This quest led Dr. Kulkarni and colleagues to establish The Australian National Register of Antipsychotic Medication in Pregnancy, in 2005. The dataset includes extensive records of mothers’ medical events and mental health assessments during pregnancy, obstetric outcomes, and one-year postpartum follow-up of mothers’ outcomes and developmental achievements of the newborns.


Kulkarni and colleagues recently published a prospective, observational study on the first 100 babies and their mothers in this dataset to undergo one-year follow-up, the first study of its kind.

“We have assembled a huge database, which enabled us to do a very detailed observational study,” says Dr. Kulkarni. “Unfortunately, we were unable to design a randomized controlled trial because of ethical considerations. We did, however, use obstetric norms as a comparator for some types of medical events in our study.”


"A significant proportion of babies in this study had either respiratory distress or drug withdrawal symptoms at birth, although there were no consistent signals of congenital anomalies."


According to Dr. Kulkarni, at this stage of their research there are no marked signals of congenital anomalies, such as limb deformities or other organ malformations, associated with atypical antipsychotic use during pregnancy. The researchers did note, however, that a significant proportion of babies in this study had either respiratory distress (37%) or drug withdrawal symptoms (15%) at birth. Babies with respiratory distress often required suction or oxygen following birth, and, for babies with Neonatal Abstinence Syndrome, conservative management in special care nurseries or a pediatrics intervention helped most newborns settle down fairly quickly. Both respiratory distress and drug withdrawal symptoms occurred more frequently in this study population compared with the obstetric norms of the general population.

Only eleven women in this sample received a typical antipsychotic, clozapine, owing to severe illness. Of the eleven babies with perinatal exposure to clozapine, two had serious congenital anomalies and showed significant intellectual delays during their first year of life.

“At this point, we’re not seeing direct and consistent teratogenic profiles of any one medication, but we are seeing other effects that are softer and just as important to the longer-term development of the child,” says Dr. Kulkarni.

The rates of polypharmacy in this sample were fairly high. With the exception of five women, all received 1–4 psychotropics, and roughly each quarter of the sample received one, two, three, or four psychotropics, respectively. Dr. Kulkarni noted that respiratory distress was six times more likely to occur in babies whose mothers received concomitant mood stabilizers. A larger sample size is needed, however, before the effects of polypharmacy can be studied in more exacting detail.


Although the data presented in this study do not specifically address the common tendency to reduce or withhold psychotropic medication during periods of the pregnancy, Dr. Kulkarni cautions against such an approach. That on-off pattern is unproven to work, and can wreak havoc on a mind and body already undergoing extraordinary physiological and hormonal fluctuations, she says.

Overall, these results suggest that perinatal antipsychotic use is associated with a higher incidence of some complications at birth, which may require specialized medical management. Clinicians should therefore ensure that female patients who require antipsychotics during pregnancy receive delivery and obstetric care in a good hospital with good pediatric facilities, where any complications can be managed appropriately.



Kulkarni J, Worsley R, Gilbert H, et al. A prospective cohort study of antipsychotic medications in pregnancy: the first 147 pregnancies and 100 one year old babies. PLoS One. 2014 May 2;9(5):e94788. doi: 10.1371/journal.pone.0094788. eCollection 2014.