What are the risks of using Adzenys (amphetamine) during pregnancy?

Adzenys (Amphetamine) Risk in Pregnancy

Adzenys can be continued during pregnancy if required for daily functioning, as amphetamines are not associated with major congenital malformations, and the documented risks are very low in magnitude. 1

Overall Safety Profile

Amphetamines do not appear to be associated with major congenital malformations, including cardiac malformations, or other significant adverse obstetrical or developmental outcomes. 2, 1 The research on potential teratogenicity of ADHD medications, particularly stimulants, is largely reassuring with a low risk of major malformations. 1

A recent, large, well-controlled study demonstrated no increased risks for amphetamine use during pregnancy on long-term outcomes including neurodevelopmental psychiatric disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment. 2

Small Potential Risks to Monitor

While overall reassuring, there are several small potential risks that warrant monitoring:

Gastroschisis

• Possible increased risk (adjusted OR 3.0; 95% CI, 1.2-7.4), but this comes from one study with possible confounding, and the absolute risk remains extremely small given the population prevalence of only 0.05%. 1

Preeclampsia

• Possible small increased risk (adjusted RR 1.29; 95% CI, 1.11-1.49), though other studies have not found this association. 1, 3
• Monitor blood pressure regularly throughout pregnancy. 1

Preterm Birth

• Possible small increased risk when stimulant use continues in the second half of pregnancy (adjusted RR 1.30; 95% CI, 1.10-1.55). 1, 3
• In the worst case scenario, the number needed to harm is about 63 for amphetamine exposure and preeclampsia, and larger (>500) for other adverse outcomes. 3

Spontaneous Abortion

• Possible increased risk for spontaneous abortion, but confounding by indication cannot be ruled out. 2

Risks of Discontinuing Treatment

Discontinuing psychostimulant treatment during pregnancy leads to worse mental health outcomes and significant functional impairments in the pregnant individual. 1 Untreated ADHD is associated with increased risks for spontaneous abortion and preterm birth. 1

The functional impairment from untreated ADHD can significantly impact the ability to care for oneself safely during pregnancy, overall mental health, and management of co-occurring conditions. 4

Management Algorithm

Continue Treatment If:

• The medication is required for daily functioning of the pregnant person. 1
• The magnitude of documented risks is very low compared to the risks of untreated ADHD. 1

Dosing Strategy:

• Use the lowest effective dose that maintains adequate daily functioning. 1
• Consider intermittent use on an as-needed basis to maximize functioning while reducing overall fetal exposure, given that stimulants have rapid effects. 1

Required Monitoring:

• Blood pressure checks regularly for preeclampsia risk. 1
• Fetal growth monitoring throughout pregnancy. 1
• Ensure appropriate maternal weight gain. 1
• Monitor infant carefully for irritability, insomnia, and feeding difficulty at birth. 1

FDA Labeling Information

The FDA classifies dextroamphetamine as Pregnancy Category C. 5 Dextroamphetamine has shown embryotoxic and teratogenic effects in mice at doses approximately 41 times the maximum human dose, but embryotoxic effects were not seen in rabbits at 7 times the human dose nor in rats at 12.5 times the maximum human dose. 5

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight, and may experience symptoms of withdrawal including dysphoria, agitation, and significant lassitude. 5

Important Caveats

This information applies to therapeutic use of amphetamines during pregnancy and does not apply to non-prescribed amphetamine use in persons with stimulant use disorder. 1, 6 Amphetamines cross the placental barrier. 6

The treating physician should engage in a risk-benefit discussion regarding continuing the currently well-tolerated, effective dose versus considering intermittent use. 1

Alternative Considerations

• Switching to bupropion is a possibility, particularly for individuals requiring treatment for co-occurring depression, given available safety data in the perinatal period, though bupropion is not as efficacious as stimulants for ADHD treatment. 1
• Dialectical Behavior Therapy (DBT) can be considered as an adjunct or alternative, with demonstrated decreased ADHD symptoms, improved neuropsychological functioning, and reduction of co-existing anxiety and depression. 1