What is the recommended management for a pregnant patient taking Aripiprazole, Fluoxetine, Ondansetron, and prenatal vitamins with iron?

Management of Aripiprazole, Fluoxetine, Ondansetron, and Prenatal Vitamins in Pregnancy

Continue all medications at their current doses with close monitoring, as the risks of untreated psychiatric illness and severe nausea outweigh the potential fetal risks, but implement specific neonatal monitoring protocols at delivery. 1, 2, 3

Fluoxetine (40 mg daily) - Continue

• The American Academy of Pediatrics recommends continuing SSRI treatment during pregnancy at the lowest effective dose, because withdrawal of medication may have harmful effects on the mother-infant dyad. 2, 3

• Discontinuing psychiatric medications during pregnancy leads to worse mental health outcomes and significant functional impairment. 2

• Untreated anxiety and mood disorders during pregnancy carry their own risks to both mother and fetus. 2

• Neonates exposed to SSRIs late in the third trimester commonly develop neonatal adaptation syndrome (agitation, irritability, tremors, poor feeding, respiratory distress) requiring prolonged hospitalization, respiratory support, and tube feeding. 2, 3

• These symptoms typically onset within several hours to several days after birth and resolve within 1-2 weeks. 2, 3

• Intrauterine antidepressant exposure does not substantially increase risk for autism spectrum disorder or ADHD. 2

• Arrange early neonatal follow-up after delivery, as infants are at risk for withdrawal or toxicity symptoms over the first week of life. 3

Aripiprazole (5 mg daily) - Continue with Caution

• The FDA label warns that aripiprazole may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder) in neonates. 4

• Limited data exist on aripiprazole use in pregnancy, but recent well-designed studies do not report fetal risk, therefore where clinically justifiable it can be used in pregnancy, ideally with the lowest effective dose. 5

• Abrupt withdrawal should be avoided. 5

• Inform the pediatric team about maternal aripiprazole exposure so they can anticipate and manage neonatal symptoms if they occur. 3

Ondansetron (4 mg every 6 hours PRN) - Use with Specific Counseling

Ondansetron is compatible with all trimesters of pregnancy per the 2023 EASL guidelines, but requires informed consent about the small absolute risk of orofacial clefting. 5

Risk-Benefit Context:

• Ondansetron use in pregnancy has been associated with an increased rate of orofacial clefting, but the absolute risk increases from a background risk of 11 cases per 10,000 births to 14 cases per 10,000 births. 5

• This risk should be put into context when advising women regarding this medication versus the risk of untreated disease. 5

• The 2023 EASL guidelines list ondansetron as compatible with first, second, and third trimesters and breastfeeding. 5

Critical Drug Interaction Warning:

• Be aware of potential serotonin syndrome risk when combining ondansetron (a serotonergic antiemetic) with fluoxetine (an SSRI). 1

• Monitor for signs of serotonin syndrome: agitation, confusion, fever, tachycardia, tremor, hyperreflexia, and hypertonia. 1

• Ondansetron has stronger serotonergic properties than metoclopramide, making this combination higher risk. 1

Alternative Antiemetic Options:

• If nausea control is inadequate or serotonin syndrome concerns arise, switch to metoclopramide as the preferred second-line agent, which has fewer side effects and weaker serotonergic properties. 1

• Metoclopramide showed no significant increase in major congenital defects in a meta-analysis of 33,000 first-trimester exposures (odds ratio 1.14,99% CI 0.93-1.38). 1

• Promethazine is an acceptable alternative H1-receptor antagonist with extensive clinical experience and no increased risk of congenital defects. 5, 1

• Drug-induced extrapyramidal symptoms and oculogyric crises can occur with phenothiazines and metoclopramide; if these symptoms occur, withdraw the drug immediately. 5

Prenatal Vitamins with Iron - Continue

• The USPSTF recommends 27 mg of elemental iron daily during pregnancy, which both prenatal formulations provide. 5

• The patient is receiving duplicate prenatal vitamins (28 mg and 27 mg iron formulations). 5

• Consolidate to a single prenatal vitamin containing 27-30 mg of elemental iron to avoid excessive iron intake and gastrointestinal side effects. 5

• Iron deficiency anemia prevalence in pregnant women is estimated at 18.6%, with higher rates in later trimesters. 5

Neonatal Monitoring Protocol at Delivery

Inform the obstetric and pediatric teams about all maternal medications to ensure appropriate neonatal monitoring for: 2, 3, 4

• Neonatal adaptation syndrome from fluoxetine exposure (irritability, feeding difficulties, respiratory symptoms) 3
• Extrapyramidal symptoms and withdrawal from aripiprazole exposure 4
• Respiratory depression monitoring if prolonged benzodiazepine-like effects occur 5

Postpartum Considerations

• The postpartum period is the highest-risk period for mood and anxiety disorder relapse. 2

• Close monitoring is essential, and consideration should be given to resuming full therapeutic dosing immediately postpartum if any dose reductions were made. 2

• Fluoxetine is excreted in human milk, but this must be weighed against benefits of breastfeeding and risks of untreated maternal psychiatric illness. 2

• Ondansetron is compatible with breastfeeding per EASL guidelines. 5