What are the risks of using Latuda (lurasidone) in pregnancy, particularly regarding increased anxiety at initiation?

Latuda (Lurasidone) Use in Pregnancy and Anxiety at Initiation

Primary Recommendation

Lurasidone does not appear to be a major teratogen based on the best available prospective registry data, with a malformation rate of 2.19% compared to 1.77% in unexposed controls (OR 1.24,95% CI 0.36-4.32), showing no statistically significant increase in risk. 1

However, lurasidone serum concentrations decrease substantially during pregnancy due to physiologic changes, which may worsen psychiatric symptoms including anxiety, particularly after the second trimester. 2

Pregnancy Safety Profile

Malformation Risk

• The National Pregnancy Registry for Psychiatric Medications prospectively followed 134 women exposed to lurasidone during pregnancy and found no specific patterns of malformations in exposed infants. 1
• The absolute risk of major malformations (2.19%) was not significantly different from unexposed controls (1.77%), with an odds ratio of 1.24 (95% CI 0.36-4.32). 1
• No evidence suggests lurasidone is a major teratogen, though additional data are needed to refine risk estimates. 1

Neonatal Adaptation Concerns

• While specific data for lurasidone are limited, neonates exposed to psychotropic medications late in pregnancy may develop complications requiring prolonged hospitalization, including respiratory distress, feeding difficulty, jitteriness, irritability, tremor, hypertonia, and seizures. 3
• These neonatal signs typically arise immediately upon delivery and resolve within 1-2 weeks, though some cases persist up to 4 weeks. 3

Anxiety Worsening at Initiation and During Pregnancy

Pharmacokinetic Changes During Pregnancy

• Lurasidone serum concentrations drop dramatically during pregnancy, ranging from 0 to 4.7 ng/mL during pregnancy compared to 10-12 ng/mL postpartum in documented cases. 2
• This substantial decrease in drug levels occurs particularly after the second trimester and may directly contribute to worsening anxiety and depressive symptoms. 2
• One documented case required a 40 mg daily dose increase during the second half of pregnancy due to worsening anxiety and depressive symptoms associated with declining lurasidone levels. 2

Akathisia and Anxiety-Like Symptoms

• Lurasidone may cause akathisia, particularly at treatment initiation, which can manifest as subjective anxiety, restlessness, and agitation. 4
• Akathisia is one of the most common adverse events associated with lurasidone treatment. 5
• Distinguishing between true anxiety worsening and medication-induced akathisia is critical, as management strategies differ fundamentally.

Clinical Management Algorithm

Before Initiating Lurasidone in Pregnancy

1. Assess baseline anxiety severity and document specific symptoms to distinguish later between disease progression, akathisia, and medication effects.

2. Counsel about the need for dose adjustments during pregnancy due to predictable decreases in serum concentrations. 2

3. Plan for therapeutic drug monitoring if available, particularly after the second trimester when concentrations decline most significantly. 2

During Treatment

1. Monitor closely for akathisia in the first 1-2 weeks after initiation or dose increases, presenting as restlessness, inability to sit still, and subjective inner tension. 4

2. If anxiety worsens after the second trimester, consider that declining lurasidone levels may be responsible rather than treatment failure or akathisia. 2

3. Dose increases of 20-40 mg daily may be necessary during the second half of pregnancy to maintain therapeutic effect. 2

4. Ensure lurasidone is taken at night with food, as absorption is reduced by 50% on an empty stomach, which could further compromise efficacy. 4

Postpartum Management

1. Reduce lurasidone to pre-pregnancy doses immediately postpartum, as concentrations increase substantially (from 0-4.7 ng/mL during pregnancy to 10-12 ng/mL postpartum). 2

2. Monitor breastfed infants for diminished suck, sleep disturbances, decreased growth, irritability, and feeding difficulties. 3

3. Arrange early follow-up after initial hospital discharge for infants exposed to lurasidone in utero. 3

Common Pitfalls to Avoid

• Do not assume anxiety worsening during pregnancy represents treatment failure or disease progression without considering declining drug levels as the primary cause. 2

• Do not mistake akathisia for anxiety disorder worsening, as akathisia requires dose reduction or adjunctive treatment (beta-blockers, benzodiazepines), while true anxiety may require dose increases. 4

• Do not maintain the same dose throughout pregnancy expecting consistent therapeutic effect, as physiologic changes predictably reduce lurasidone concentrations. 2

• Do not continue pregnancy doses postpartum, as this may lead to excessive drug exposure and adverse effects given the rapid normalization of pharmacokinetics. 2

• Do not discontinue treatment solely due to pregnancy if the medication is required for daily functioning, as untreated psychiatric illness carries its own substantial risks. 6