USE OF RISPERIDONE IN PREGNANCY

Risperidone is an atypical antipsychotic (AAP) used in the treatment of schizophrenia, mania, and for the short-term management of persistent aggression.

Congenital malformation risks following risperidone exposure have been described for a collective total of ~2,240 pregnancies. While a meta-analysis of data from 432 exposed pregnancies and a small cohort study (n=242 exposures) did not find increased risk of any major malformation, a large cohort study incorporating the remaining exposures identified a statistically significant 1.26-fold increased risk. Two cohort studies have found no increased risk of cardiac defects specifically. One of these studies also did not identify increased risks for malformations of other specific organ systems (CNS, respiratory tract, orofacial cleft, gastrointestinal, urogenital, musculoskeletal).

Data relating to other pregnancy outcomes following maternal risperidone exposure are either extremely limited or are absent, thus precluding evidence-based risk assessments. A single study did not find an increased risk of a range of adverse neurodevelopmental outcomes among 1,400 children exposed to risperidone in the second half of gestation. Potential users should be made aware of the paucity of data, and the decision to prescribe in pregnancy made on a case-by-case basis.

Studies of antipsychotics (APs)/AAPs as therapeutic classes that include a collective total of >50,000 exposures are largely reassuring for most outcomes. However, data relating to stillbirth risks are conflicting, and similarly, associations have been described for first generation AP exposure with preterm delivery and small for gestational age, and preterm delivery and AAP exposure, though these data are also conflicting and likely confounded. These data do not provide compelling evidence of causal associations, and further research is required to confirm or refute these findings.

In the non-pregnant population, use of AAPs (particularly olanzapine, clozapine and quetiapine) is a risk factor for impaired glucose homeostasis and type 2 diabetes. Concerns therefore exist regarding an increased risk of maternal gestational diabetes mellitus (GDM) and its sequelae following gestational risperidone use. A single small study found that women taking risperidone in pregnancy were at ~3-fold increased risk of gestational diabetes, and a cohort study reported a gestational diabetes rate of 18.2% in risperidone-exposed pregnancies. Data investigating AAPs generally have also identified increased risks of infant birth weight >97th centile. Enhanced diabetes screening for all women prescribed APs (with oral glucose tolerance test) is advised.

Use of risperidone and other APs throughout pregnancy or near delivery has been associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug. Delivery should therefore be planned in a unit with neonatal intensive care facilities.

It is important to ensure that maternal mental health conditions are treated appropriately. Where a woman’s illness is well-controlled on risperidone, either prior to conception or during pregnancy, the risk of discontinuing or changing medication, or reducing the dose, should be carefully weighed against the risk of relapse. Where clinically appropriate, clinicians are encouraged to discuss the advantages and disadvantages of continued risperidone use during pregnancy with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, risperidone may be prescribed for use in pregnancy.