Is Latuda (lurasidone) safe during pregnancy?

Latuda (Lurasidone) Safety in Pregnancy

Latuda can be used during pregnancy when the maternal benefit justifies the potential fetal risk, but it is not a first-line choice and should be avoided in the first trimester if possible. The FDA label explicitly states that neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal and/or withdrawal symptoms, and there are no adequate studies in pregnant women to definitively establish safety 1.

Key Safety Considerations

FDA Pregnancy Classification and Registry

• The FDA label indicates there is a pregnancy exposure registry (National Pregnancy Registry for Atypical Antipsychotics: 1-866-961-2388) that monitors outcomes in women exposed to lurasidone during pregnancy 1.
• Animal reproduction studies showed no teratogenic effects at doses up to 1.5 times (rats) and 6 times (rabbits) the maximum recommended human dose, but animal data cannot be directly extrapolated to humans 1.
• The estimated background risk of major birth defects in the U.S. general population is 2-4%, and miscarriage is 15-20% 1.

Clinical Evidence on Malformation Risk

• The most recent and highest quality evidence comes from a 2023 prospective cohort study (National Pregnancy Registry) showing an absolute risk of major malformations of 2.19% with lurasidone exposure versus 1.77% in unexposed controls, with an odds ratio of 1.24 (95% CI 0.36-4.32), indicating no statistically significant increased risk 2.
• A 2025 network meta-analysis found that lurasidone should be approached with caution during pregnancy, as the evidence base is limited and further clinical studies are needed to better assess its safety 3.
• No specific patterns of malformations have been identified with lurasidone exposure 2.

Neonatal Complications

• Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal symptoms (hypertonia, tremor) and/or withdrawal symptoms (agitation, hypotonia, somnolence, respiratory distress, feeding disorder) 1.
• These symptoms vary in severity; some neonates recover within hours to days without treatment, while others require prolonged hospitalization 1.
• All neonates exposed to lurasidone in the third trimester must be monitored for these complications and managed appropriately 1.

Pharmacokinetic Changes During Pregnancy

• Lurasidone serum concentrations decrease significantly during pregnancy (ranging from 0-4.7 ng/mL) compared to postpartum levels (10-12 ng/mL), which may increase the risk of bipolar disorder symptom exacerbation 4.
• This decrease in drug levels may necessitate dose increases during pregnancy to maintain therapeutic efficacy, particularly after the second trimester 4.
• Therapeutic drug monitoring should be considered to optimize dosing and minimize illness relapse 4.

Risk-Benefit Analysis

When Treatment is Justified

• Untreated bipolar disorder in pregnancy is associated with significantly higher rates of premature delivery and low birth weight compared to treatment with mood stabilizers including lurasidone 5.
• A 2024 retrospective cohort study demonstrated that women with untreated bipolar disorder had worse neonatal outcomes than those treated with lurasidone, other atypical antipsychotics, or lamotrigine 5.
• The maternal benefit of treating severe psychiatric illness must be weighed against the potential fetal risk, particularly when untreated illness poses substantial risks to both mother and fetus 1.

Safer Alternatives to Consider First

• Quetiapine has the lowest teratogenic risk among atypical antipsychotics according to the 2025 network meta-analysis, with an odds ratio of 1.19 (95% CrI 1.01-1.39) for congenital malformations 3.
• Lamotrigine showed no significant difference in malformation risk compared to unexposed controls (OR 1.21; 95% CrI 0.86-1.64) with narrower credible intervals 3.
• Haloperidol also did not show significant differences (OR 1.26; 95% CrI 0.90-1.75) 3.

Clinical Decision Algorithm

First Trimester (Organogenesis Period)

• Avoid lurasidone during the first trimester if possible, as this is the period of highest teratogenic risk when fetal organs are forming 6, 7.
• If treatment is essential, consider switching to quetiapine or lamotrigine, which have more favorable safety profiles 3.
• Document clear medical indication where maternal benefit outweighs unknown fetal risk 8.

Second and Third Trimesters

• Lurasidone may be continued or initiated if non-pharmacologic measures and safer alternatives have failed, and the maternal benefit clearly outweighs potential fetal risk 8.
• Use the lowest effective dose for the shortest possible duration 8.
• Monitor for decreased drug levels and worsening psychiatric symptoms, particularly after the second trimester 4.
• Consider dose adjustments based on clinical response and therapeutic drug monitoring if available 4.

Third Trimester Specific Considerations

• Plan for neonatal monitoring at delivery for extrapyramidal and withdrawal symptoms 1.
• Coordinate care with neonatology team to ensure appropriate observation and management of potential neonatal complications 1.
• Do not discontinue medication abruptly before delivery, as this may precipitate maternal psychiatric decompensation without eliminating neonatal risk 1.

Common Pitfalls to Avoid

• Do not assume that absence of data equals safety—lurasidone has limited human pregnancy data, representing an unknown risk that warrants caution 8.
• Do not discontinue effective treatment without a plan for alternative management, as untreated bipolar disorder carries its own substantial risks to pregnancy outcomes 5.
• Do not fail to counsel patients about the pregnancy registry—enrollment provides valuable safety data and may benefit future patients 1.
• Do not neglect to adjust dosing during pregnancy—physiologic changes significantly reduce lurasidone levels and may lead to treatment failure 4.