Virginia Via Research Day Book 2026

Medical Student Research Clinical

17 PSYCHOMOTOR OUTCOMES OF CLOZAPINE USE DURING PREGNANCY: A SCOPING REVIEW

Elizabeth Tucker, OMS-II; Arundhati Rajpurohit, OMS-III; Bernard Kadio, MD, MPH, PhD Corresponding author: etucker@vcom.edu

VCOM-Virginia, Blacksburg, Virginia

pregnancy is inevitable. In animal models, clozapine causes a dose-dependent suppression of locomotor activity in zebrafish larvae, producing significant reductions in swimming distance and velocity with associated disruptions in serotonergic and dopaminergic signaling. Similarly, in male rats, clozapine treatment has been found to induce a persistent hypolocomotor effect. There is scant and scattered evidence on the long term effects of clozapine exposure in utero in humans. Objective and/or Hypothesis: This new research aimed at mapping the extent, range, and nature of the available body of research on psychomotor outcomes in children exposed to clozapine in utero. Methods: We used a scoping study method to identify, analyze, and synthesize available evidence published between 2002-2024. Twenty-five (25) papers were included in the review, and the study protocol was registered on PROSPERO. The identified outcomes were mapped using a concept tree that consisted of five branches, each corresponding to an identified outcome.

Context: Clozapine is a dibenzodiazepine primarily prescribed for the treatment of schizophrenia. Unlike first-line antipsychotic medications, clozapine is reserved for treatment-resistant cases or for individuals at high risk of recurrent suicidal behavior. Its therapeutic efficacy stems from its ability to modulate the activity of dopamine and serotonin pathways. In the United States, 4% of patients with schizophrenia are prescribed clozapine despite an estimated 30% meeting criteria for treatment-resistant schizophrenia. Women make up 42% of clozapine-treated Medicaid patients. During pregnancy, clozapine has been associated with maternal side effects, including gestational diabetes, increased body mass index, and an greater risk of miscarriage. The drug crosses the placenta and is detected in amniotic fluid. This makes the prescription of clozapine very limited during pregnancy, less than 1 for 10,000 births in countries like Norway and Australia. However, we were able to create a Clozapine Cohort consisting of 23,446 pregnant mothers from the All of Us database, suggesting that clinicians might be confronted with clinical scenarios where prescription of this drug during

Results: Two papers reported language and cognitive concerns in the offspring of mothers taking clozapine during pregnancy; seven papers reported sleeping or feeding issues; two papers reported neonatal withdrawal symptoms; three papers reported psychomotor delay; eight papers reported normal psychomotor development. Conclusion(s): However, the studies have some strong limitations in that no long-term follow-up was reported. These findings suggest that if clozapine is to be prescribed during pregnancy, additional long-term follow-up might be needed in the offsprings to mitigate potential adverse effects on psychomotor development. We sent our review for consultation to the American Board of Pediatric Neuropsychology.

Table of Contents

188 Edward Via College of Osteopathic Medicine (VCOM)