January 13, 2026

Obstetric Outcomes After Exposure to Second-Generation Long-Acting Injectable Antipsychotic Medications

Pregnancy & Medications

Exposure to long-acting injectable and oral second-generation antipsychotics during pregnancy was associated with similar obstetric outcomes in a large retrospective study.

Ruta Nonacs, MD PhD

Newer atypical, or second-generation, antipsychotic agents are commonly used to treat a spectrum of psychiatric disorders, including schizophrenia, bipolar disorder, major depression, PTSD, and anxiety disorders. Data from retrospective and prospective studies suggest that exposure to atypical antipsychotics during pregnancy does not appear to be associated with an increased risk of major congenital malformations, although inconsistent findings have been reported with risperidone and paliperidone use during pregnancy.

Most of the existing data on atypical antipsychotics are specific to oral formulations, with far less information available on outcomes related to long-acting injectable (LAI) antipsychotics. LAIs offer several advantages for individuals with serious mental illness, particularly those with a history of poor adherence to oral medications. By providing consistent medication exposure and reducing the risk of nonadherence, LAI antipsychotics may play a crucial role in managing psychiatric illness during pregnancy. However, it is unclear whether findings from studies on oral antipsychotics can be extrapolated to LAI formulations.

A recent study explored obstetric outcomes in pregnant women treated with second-generation LAI antipsychotics compared to a control group receiving second-generation oral antipsychotics.

Study Design

This retrospective study analyzed data from a global cohort of 148 health care organizations included in the TriNetX database. Pregnant patients with exposure to atypical antipsychotics were grouped into two cohorts:

Long-acting injectable antipsychotics: aripiprazole, risperidone, paliperidone, or olanzapine (n=2,082)
Corresponding oral formulations: n=31,376, with propensity matching

To create a balanced comparison group, propensity score matching was applied using 26 variables, including demographic characteristics (such as age and race), social determinants of health, medical and psychiatric comorbidities, and concomitant psychotropic use.

The study examined the occurrence of the following obstetric complications: gestational diabetes, preeclampsia, eclampsia, or newly diagnosed hypertensive disorders. Rates of cesarean section were also assessed.

Study Results

The mean age of participants was 30 years. White (47%) and Black (40%) patients were the most commonly represented racial groups. Most participants had bipolar disorder (47%) or schizophrenia (30%). Anxiety disorders, major depressive disorder, and nicotine use disorder were also common, diagnosed in 44%, 39%, and 42% of participants, respectively. Concomitant use of antidepressants (61%) and sedative/hypnotic medications (66%) was frequent.

After propensity matching, each cohort included 2,025 patients. Similar rates of gestational diabetes, preeclampsia, eclampsia, and hypertensive disorders were observed among women receiving long-acting injectable versus oral second-generation antipsychotics. Rates of cesarean section did not differ between groups.

Clinical Implications

Comparable obstetric outcomes were observed in pregnant women treated with either long-acting injectable or oral second-generation antipsychotics. These findings support the potential safety of LAI atypical antipsychotic agents during pregnancy, particularly for women in whom the risks of untreated psychiatric illness outweigh potential medication-related adverse effects.

– Ruta Nonacs, MD PhD