Clozapine placental passage at delivery: an update

Introduction Clozapine is an effective second-generation antipsychotic that is approved for treatment-resistant schizophrenia and risk reduction of recurrent suicidal behavior in schizophrenia or schizoaffective disorder. Its available pregnancy pharmacikinetics data remain limited, which presents a challenge for clinicians managing women taking clozapine during perinatal period . Objectives The aim of this study was to provide new data of clozapine and norclozapine placental passage and neonatal outcomes. Methods We retrospectively studied a consecutive case series of six pregnancies where there was clozapine exposure (5 in politherapy and 1 in monotherapy). Clozapine and norclozapine serum concentrations were determined in the mother-infant pairs on the day of delivery (intrapartum maternal blood and umbilical cord blood respectively) and measured using a validated high-performance liquid chromatography method. The within- and between-day precision expressed as the coefficient of variation (CV)% were both <10%. The limit of quantification (LoQ) was 5 ng/mL. Neonatal outcomes were reviewed from pediatric records. Results The mean infant-mother clozapine and norclozapine ratio at delivery were 0.44 (SD=0.13) and 0.28 (SD=0.05) respectively. There was a weak positive correlation between maternal and umbilical cord clozapine and norclozapine serum concentratios (Pearson correlation coefficient 0.183, p=0.769 and 0.827, p=0.084 respectively). The rate of neonatal complications was 16%. One neonate (16%) , whose mother had drug abuse history during pregnancy, presented with a generalized neurodevelopment delay and the consequent need for continuous intensive care. Conclusions In our study, placental passage of clozapine and norclozapine was partial during delivery. Statistical power was limited for examining te association between neonatal clozapine levels and neonatal outcomes. Disclosure No significant relationships.