Is Vyvanse (lisdexamfetamine) safe to use during pregnancy, particularly in patients with a history of substance abuse or Attention Deficit Hyperactivity Disorder (ADHD)?

Vyvanse Safety in Pregnancy

Vyvanse (lisdexamfetamine) does not appear to cause major congenital malformations and can be continued during pregnancy when required for daily functioning, though it carries small increased risks for gastroschisis, preeclampsia, and preterm birth that warrant informed discussion. 1

Evidence on Major Malformations

• Amphetamines, including lisdexamfetamine, do not appear to be associated with major congenital malformations, including cardiac malformations, or other significant adverse developmental outcomes. 1
• A 2023 registry study found no major malformations in infants exposed to lisdexamfetamine during the first trimester, with an odds ratio of 0.39 (95% CI, 0.09-1.61) for any stimulant compared to controls. 2
• A large 2023 Danish cohort study of 898 children exposed to ADHD medications in utero found no increased risk of neurodevelopmental disorders (adjusted HR 0.97,95% CI 0.81-1.17) after controlling for maternal psychiatric characteristics. 3
• A 2024 US study of over 4 million pregnancies found that amphetamine/dextroamphetamine exposure was not associated with autism spectrum disorder (HR 0.80,95% CI 0.56-1.14), ADHD (HR 1.07,95% CI 0.89-1.28), or any neurodevelopmental disorder (HR 0.91,95% CI 0.81-1.28) after adjustment. 4

Small but Measurable Risks

While major malformations are not increased, the American College of Obstetricians and Gynecologists identifies specific risks that require counseling:

• Gastroschisis: Adjusted odds ratio 3.0 (95% CI, 1.2-7.4), though the absolute risk remains small. 1
• Preeclampsia: Adjusted relative risk 1.29 (95% CI, 1.11-1.49) with lisdexamfetamine use. 1
• Preterm birth: Continued stimulant use in the second half of pregnancy carries an adjusted relative risk of 1.30 (95% CI, 1.10-1.55). 1

Clinical Decision-Making Algorithm

When ADHD medication is required for daily functioning:

• Continue lisdexamfetamine during pregnancy, as the functional impairment from untreated ADHD can significantly impact ability to care for oneself and prepare for a child. 1
• Counsel patients on the small increased risks of gastroschisis, preeclampsia, and preterm birth. 1
• Monitor for signs of preeclampsia throughout pregnancy, particularly in the second half. 1

When ADHD symptoms are mild or manageable without medication:

• Consider non-pharmacological interventions for ADHD during pregnancy as recommended by the American College of Obstetricians and Gynecologists. 1
• Attempt discontinuation before pregnancy if feasible. 1

Important Caveats

• Lisdexamfetamine crosses the placental barrier, as do all amphetamines, which is the biological basis for monitoring but does not indicate harm. 1
• Limited published information exists specifically on lisdexamfetamine use during pregnancy, so risk information is extrapolated from amphetamine class data. 1
• This guidance applies only to therapeutic use at prescribed doses, not to stimulant use disorder or non-prescribed amphetamine use. 1

Neonatal Monitoring

• Monitor infants carefully for irritability, insomnia, and feeding difficulties if the mother was taking amphetamines during pregnancy. 1
• These symptoms are typically transient and manageable with supportive care. 1

Substance Abuse History Considerations

The evidence on safety applies to therapeutic use in patients with ADHD, regardless of past substance abuse history, as long as the medication is being used as prescribed. 1 The prodrug formulation of lisdexamfetamine has lower abuse potential compared to other stimulants, making it a reasonable choice in this population. 1