Comparative Safety of Antipsychotic Medications and Mood Stabilizers During Pregnancy: A Systematic Review and Network Meta-analysis of Congenital Malformations and Prenatal Outcomes

A network meta-analysis was performed to evaluate the risk of congenital malformations and other prenatal outcomes in fetuses after exposure to antipsychotic medications and mood stabilizers during pregnancy.

We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to 13 December 2023, to identify experimental and observational studies comparing antipsychotic and mood stabilizer treatments with control treatments (no exposure). The primary outcome of the study was the incidence of congenital malformations and the secondary outcomes were preterm birth and spontaneous abortion. Additionally, two authors independently assessed the risk of bias in each domain of the included studies using the ROBINS-I tool and evaluated the quality of evidence using the CINeMA rating tool.

The literature search identified 18,334 potential records, and 21 studies involving 1,701,089 pregnant women were ultimately included. Compared with the unexposed group, aripiprazole [odds ratio (OR), 1.29; 95% credible interval (CrI), 1.001–1.93] was associated with a slightly increased risk of congenital malformations. In contrast, lamotrigine (OR, 1.19; 95% CrI, 0.72–1.85), quetiapine (OR, 1.13; 95% CrI, 0.81–1.44), olanzapine (OR, 1.33; 95% CrI, 0.98–1.87), risperidone (OR, 1.35; 95% CrI, 0.96–1.93), and haloperidol/penfluridol (OR, 1.43; 95% CrI, 0.90–2.17) did not show significant differences compared with the unexposed group, with narrower credible intervals.

The evidence from this analysis suggests that, overall, quetiapine is currently the most rational choice among second-generation antipsychotics regarding safety and clinical utility. Among mood stabilizers, lamotrigine appears to be a relatively safer option. Haloperidol remains a viable alternative under close monitoring. At the same time, the use of lurasidone and ziprasidone should be approached with caution, and further clinical studies are necessary to better assess their safety.

PROSPERO CRD4201811373.