Does risperidone (antipsychotic) transfer into breast milk and is it safe to breastfeed while taking it?

Risperidone Transfer into Breast Milk

Yes, risperidone does cross into breast milk, but at relatively low concentrations; however, serious adverse effects including respiratory depression have been reported in breastfed neonates, making this a high-risk medication that requires careful consideration of alternatives and, if used, close infant monitoring.

FDA Drug Label Position

The FDA label explicitly states that "risperidone and 9-hydroxyrisperidone are present in human breastmilk" and recommends that "because of the potential for serious adverse reactions in nursing infants from risperidone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother." 1

Pharmacokinetic Data on Milk Transfer

Milk-to-plasma ratio and infant exposure:

• The milk/plasma concentration ratio is <0.5 for both risperidone and its active metabolite 9-hydroxyrisperidone 2
• Drug levels in breast milk are approximately ten-fold lower compared to maternal serum 3
• The calculated relative infant dose (RID) ranges from 2.3% to 4.7% of the maternal weight-adjusted dose, which is below the arbitrary 10% safety threshold 2

Critical Safety Concerns

Case report of serious adverse event:

• A 2023 case report documented respiratory depression in a preterm neonate whose mother was taking only 1 mg/day of risperidone—well below typical therapeutic doses 4
• The respiratory depression occurred twice in this infant, with a Naranjo Adverse Drug Reaction Probability Scale score of 8 (probable causation) 4
• This represents the first reported case where such a low dose caused acute life-threatening effects 4

Variability in drug metabolism:

• Risperidone excretion depends on CYP2D6 enzyme activity, which varies significantly based on individual phenotype 4
• This genetic variability means some infants may be at higher risk regardless of maternal dose 4

Clinical Decision Algorithm

When risperidone use is being considered in a breastfeeding mother:

1. First-line approach: Explore alternative antipsychotics with better safety profiles in lactation, or consider discontinuing breastfeeding if risperidone is medically necessary 1

2. If risperidone must be used:

   • Use the lowest effective maternal dose 1
   • Time breastfeeding to occur just before the next maternal dose (maximum drug levels occur 2 hours post-administration) 4
   • Monitor the infant closely for sedation, poor feeding, respiratory depression, and developmental delays 1, 4

3. Infant monitoring parameters:

   • Respiratory rate and effort at each feeding 4
   • Level of alertness and feeding vigor 3
   • Weight gain and developmental milestones 3
   • Consider measuring infant plasma levels if any concerning symptoms develop 2

Evidence Quality and Limitations

While earlier studies from 2004-2005 suggested relative safety with no detectable plasma levels in infants and no adverse effects 3, 2, the 2023 case report of respiratory depression at very low maternal doses fundamentally changes the risk-benefit calculation 4. The genetic variability in CYP2D6 metabolism means that population-level RID calculations may not predict individual infant risk 4.

Common Pitfalls to Avoid

• Do not assume low RID guarantees safety: The 2023 case demonstrates serious toxicity can occur despite favorable pharmacokinetic parameters 4
• Do not overlook preterm or low-birth-weight infants: These populations have immature drug metabolism and are at higher risk 4
• Do not fail to counsel on timing: Advise mothers that peak drug levels occur 2 hours after dosing 4