Antipsychotic use during pregnancy and outcomes in pregnant individuals and newborns

Background: Despite the increasing use of antipsychotics during pregnancy, comprehensive evaluations of their individual safety profiles using global data remain limited. This study aimed to assess the safety of various antipsychotics during pregnancy by comparing them to quetiapine, which has a relatively large body of safety data. Method: Utilizing the World Health Organization pharmacovigilance database (1968–2023; n = 131,255,418 reports), we identified 11,406 reports of antipsychotic exposure during pregnancy. A disproportionality analysis was performed to calculate reporting odds ratios (RORs) for adverse pregnancy, fetal, or neonatal outcomes associated with haloperidol, ziprasidone, clozapine, olanzapine, risperidone, aripiprazole, and paliperidone, compared to quetiapine. Results: Haloperidol had a significantly higher reporting frequency for congenital malformations compared to quetiapine (ROR 3.83; 95 % CI, 2.62–5.59). No statistically significant differences were found for other antipsychotics regarding congenital malformations or neonatal complications compared to quetiapine. All studied antipsychotics had lower reporting frequencies for gestational diabetes mellitus than quetiapine (overall ROR 0.22; 95 % CI, 0.18–0.28). Haloperidol, clozapine, olanzapine, risperidone, and aripiprazole were more frequently reported for abortion or stillbirth. Paliperidone and ziprasidone had similar or lower reporting frequencies for major adverse outcomes compared to quetiapine, though conclusions regarding ziprasidone are limited by the small number of reports and the relatively high proportion mentioning adverse pregnancy outcomes. Limitations: Incomplete data and reporting bias hinder establishing causality. Conclusions: Compared to quetiapine, several antipsychotics with less established safety data, particularly ziprasidone and paliperidone, have the potential to serve as safe alternatives for use during pregnancy. However, further research is needed to verify these findings and ensure the safety of these antipsychotics as treatment options during pregnancy.