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

BACKGROUND

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.

METHODS

We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to 15 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.

RESULTS

The literature search identified 18,334 potential records, and 22 studies involving 3,042,997 pregnant women were ultimately included. Compared with the unexposed group, quetiapine [odds ratio (OR), 1.19; 95% credible interval (CrI), 1.01-1.39], aripiprazole (OR, 1.30; 95% CrI 1.10-1.65), olanzapine (OR, 1.33; 95% CrI 1.11-1.64), risperidone (OR, 1.43; 95% CrI 1.18-1.77), and lithium (OR, 1.61; 95% CrI 1.07-2.30) were associated with a slightly increased risk of congenital malformations. In contrast, lamotrigine (OR, 1.21; 95% CrI 0.86-1.64), ziprasidone (OR, 1.14; 95% CrI 0.73-1.72), and haloperidol (OR, 1.26; 95% CrI 0.90-1.75) did not show significant differences compared with the unexposed group, with narrower credible intervals.

CONCLUSIONS

The evidence from this analysis suggests that, overall, quetiapine has the lowest teratogenic risk when used during pregnancy, making it the safer option for pregnant women. Lamotrigine and haloperidol follow closely behind. 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.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4201811373.