A review of the safety of clozapine during pregnancy and lactation

Clozapine is an antipsychotic used in the management of treatment-resistant schizophrenia. However, little is known about clozapine use during pregnancy and lactation, or its impact on the mother, foetus, and infant. This review aims to summarize the available literature on the safety of clozapine use during the perinatal period. EMBASE, PsycINFO, and MEDLINE were searched from their inceptions through June 2016. The review encompasses 21 studies that have examined clozapine use during pregnancy and lactation. The limited available data do not support an increased risk of congenital malformations in foetuses exposed to clozapine during pregnancy, though rates of gestational diabetes are twice as high in pregnant women using clozapine. Clozapine accumulation in foetal serum possibly contributes to increased rates of floppy infant syndrome at delivery, decreased foetal heart rate variability, and seizures in infancy. Clozapine crosses the placenta and also accumulates in breast milk, which may increase the risk of agranulocytosis in infants and may necessitate infant testing. The majority of these data come from case reports and case series, making it unclear if the published risks associated with clozapine are due to mental illness, lifestyle factors, or co-treatment with other psychotropic medications. While the available literature on clozapine use during the perinatal period is very limited, the risks of clozapine use during pregnancy and the postpartum period should be discussed with women and weighed against those associated with other treatments and partially or untreated schizophrenia.