Association of antidepressant use during pregnancy and pregnancy-induced hypertension: a systematic review and...

The association between antenatal antidepressant use and pregnancy-induced hypertension (GH/PE) remains controversial, with conflicting evidence on whether depression itself confounds this risk.

We searched PubMed, Web of Science, Medline, Embase, Cochrane Library, and the China National Knowledge Infrastructure electronic databases from inception to Dec. 31, 2024. Eligibility criteria for selecting studies are randomized trials, cohort studies, and case-control studies exploring the association between antidepressant use during pregnancy and pregnancy-induced hypertension. Two reviewers extracted data and assessed quality. Outcomes were expressed as odds ratios with 95% confidence intervals.

Seventeen observational studies were analyzed, indicating a potential link between antidepressant use in pregnancy and an elevated risk of gestational hypertension/preeclampsia (GH/PE). Pooled odds ratios (ORs) stratified by drug class demonstrated significant associations for: Selective serotonin reuptake inhibitors (OR = 1.34; 95% CI: 1.14-1.58); Serotonin-norepinephrine reuptake inhibitors (OR = 1.94; 95% CI: 1.40-2.70); Tricyclic antidepressants (OR = 2.00; 95% CI: 1.32-3.04). Following adjustment for depression as a confounding variable, sensitivity analysis indicated: SNRIs maintained significant association with GH/PE (adjusted OR = 1.53; 95% CI: 1.25-1.88); SSRIs showed no significant risk (adjusted OR = 1.03; 95% CI: 0.97-1.10); TCAs lost statistical significance (adjusted OR = 1.80; 95% CI: 0.86-3.74). Subgroup analyses suggesting geographical variations in effect magnitude.

This study demonstrates differential associations between antenatal exposure to three antidepressant classes (SSRIs, SNRIs, TCAs) and gestational hypertension/preeclampsia risk. Enhanced blood pressure monitoring is advised during SNRI therapy, with clinical decisions requiring individualized risk-benefit assessment. Residual confounding constrains causal inference, necessitating prospective studies with standardized depression scales and systematic exposure documentation to resolve methodological limitations.

PROSPERO: CRD42025640646.