Clinical Summary
Clinical Summary: Obstetric Outcomes With Second-Generation Long-Acting Injectable Versus Oral Antipsychotics
Pregnant patients with schizophrenia or bipolar disorder often need ongoing antipsychotic treatment, and relapse risk from undertreatment can be clinically serious for both mother and fetus. Clinicians have more safety data for oral antipsychotics than for long-acting injectable antipsychotics, so this comparison directly informs whether formulation choice changes obstetric risk.
Design
This was a retrospective study utilizing a global cohort of 148 health care organizations grouped into a network within the TriNetX database called the Global Collaborative Network.
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After PSM, 2 cohorts of 2,025 patients were created for subsequent analyses.
Population
Pregnant patients greater than age 18 years were grouped into 2 cohorts: (1) exposure to an LAIA (aripiprazole, risperidone, paliperidone, or olanzapine) 7 days before or 280 days after a coded pregnancy event and (2) exposure to oral aripiprazole, risperidone, paliperidone, or olanzapine within 14 days before or 280 days after a coded pregnant event.
Duration
The time window for outcomes assessed included events started 1 day after the first occurrence of the index event and ended 280 days after the first occurrence of the index event.
Key Findings
- The composite primary obstetric outcome occurred in 8.7% of patients on oral SGAs and 8.3% of patients on corresponding LAIAs, with no significant difference after matching (OR 0.95; 95% CI, 0.76–1.18; P=.612).
- Cesarean section rates did not differ significantly between groups in the matched analysis (OR 1.09; 95% CI, 0.83–1.43; P = .537).
- Propensity score matching produced 2 cohorts of 2,025 patients, and all matching covariates achieved adequate balance, with SMDs below 0.1.
- The matched cohort was clinically complex: bipolar disorder was present in 47%, schizophrenia in 30%, anxiety disorders in 44%, major depressive disorder in 39%, nicotine use disorder in 42%, circulatory disorders in 34%, and preexisting diabetes mellitus in 11%.
Clinical Bottom Line
For pregnant women treated with second-generation antipsychotics, long-acting injectable formulations and oral formulations had similar rates of gestational diabetes and hypertensive obstetric complications. Formulation choice can be based on adherence and relapse prevention needs rather than an observed difference in these obstetric outcomes.
Practice Implications
- Do not avoid a second-generation long-acting injectable antipsychotic solely out of concern for higher rates of gestational diabetes, preeclampsia, eclampsia, or gestational hypertension when compared with the corresponding oral antipsychotic.
- When adherence is a major concern in pregnancy, long-acting injectable antipsychotics remain a reasonable option because obstetric complication rates were similar while LAIAs offer more consistent medication exposure.
- Counsel patients using absolute risks from this study: the composite obstetric outcome occurred in 8.7% of oral SGA exposures and 8.3% of LAIA exposures.
- Do not use these data to reassure patients about spontaneous abortion, congenital malformations, or broader neonatal safety, because those outcomes were not assessed in this analysis.
