80% of women in the U.S. will experience at least one pregnancy and 84% of babies will be breastfed. In addition, more than half of women use medications during lactation. There are many reasons for using medications during breastfeeding, but the post-partum period is a time of high vulnerability to mood and anxiety episodes, and the effects of a mood episode on both the mother and the infant can be catastrophic if untreated.
In other words, decisions about taking medications and breastfeeding are important ones and should be discussed before childbirth. This blog post summarizes what we know and don’t know about the subject.
Assessing Infant Exposure
There are two ways of assessing infant exposure to a medication that the mother is taking during breastfeeding:
- Milk to Plasma Ratio. This is a general measure of potential infant exposure. The milk-to-plasma ratio is often reported in the published literature. For example it is often found in LactMed.
- Relative Infant Dose (RID). This is a value that is calculated for each individual mother and infant pair based on infant and maternal weight and amount of breastmilk consumed by the infant.
Milk to Plasma Ratio
The amount of a drug present in breast milk depends on a few factors.
- The size (or molecular weight) of the drug molecule. At the very beginning and very end of breastfeeding, large molecules can pass into breast milk easily but during most of breastfeeding only small molecules get into breast milk.
- Concentration in the mother’s blood. Most medicines get into breast milk by passive diffusion, relatively few require active transport.
- Lipid solubility of the drug. More lipid soluble drugs pass into breast milk more easily.
Other Pharmacokinetic Factors
The milk to plasma ratio is a good measure of relative exposure of the infant to the drug. But other factors, specific to the mother and the infant, determine blood level in the infant.
Maternal factors. The dose the mother takes and her weight (or dose per kilogram) as well as the mother’s metabolism of the drug.
Infant factors. The amount of breast milk the infant consumes, the infant’s weight (dose per kilogram), as well as the infant’s metabolism of the drug. Premature babies may not have the same clearance abilities as full-term babies. And all babies tend to have less active cytochrome P450 systems and less effective renal clearance. In addition, the blood-brain barrier is much more permeable in a newborn than in an adult.
Risk Benefit Estimates
As with many aspects of medical practice, available literature tends to describe risks much better than benefits. In particular, no research weighs the relative risk to the infant against the relative risk to the mother or baby of not using the drugs.
There was a major change in FDA labeling. The old risk categories were retired. It was felt that the risk categories A, B, C, D, and X were misleading. There’s now much more comprehensive pregnancy and lactation labeling that replaces those categories. It contains a risk summary that includes both the effects on the infants and effects on milk production. It includes clinical considerations such as information on how to minimize exposure and offers a summary of the existing data.
SSRI medications in general have low passage into the breastmilk and all of them are considered compatible with breastfeeding.
Fluoxetine has a longer half-life which led to early anecdotal concern about increased half-life and increased case reports early on about adverse reactions but that doesn’t mean there’s reason to stop it for breastfeeding if it’s the medication that works well for the patient.
Sertraline has the lowest milk to plasma ratio.
In general, all of the other newer antidepressants have low milk to plasma ratios and appear to be safe.
For bupropion which is used frequently in women of childbearing age, there’s a theoretical concern that it could lower the seizure threshold when used in high doses. And in fact, we have one published case report of an infant who had a seizure but it’s only one published case report. What that leads you to do in the clinical situation is use this drug with caution in a baby who has other reasons for being at risk for seizure but it’s not a reason not to use the drug in babies who don’t have an excess seizure risk.
We actually have limited evidence about stimulants. They are drugs that have not been used during pregnancy and postpartum until fairly recently but that limited evidence, we have indicates that for both the methylphenidate class and the amphetamine class there’s low passage into the breastmilk. There are theoretical concerns about appetite suppression and infant growth, but these issues have not been well studied.
The use of benzodiazepine is not contraindicated but it’s something that we have to do with caution because of these possible effects on the child.
Buspirone, we know produces low levels in the breastmilk but there are very limited data about any long-term or adverse effects.
And hydroxyzine, we know that small occasional doses are considered compatible. There are some case reports of adverse effects chiefly sedation for more long-term usage.
First-generation antipsychotics are considered compatible with breastfeeding.
The same is true for most second-generation antipsychotics but we have no data on the newest drugs, for example, brexpiprazole and cariprazine. Quetiapine is the atypical that has the lowest passage into the breastmilk due to the large size of the molecule.
It’s always better to use an older drug with more data if it’s possible to keep the mother well that way.
The one antipsychotic that’s nearly always contraindicated in breastfeeding is clozapine due to the risk for agranulocytosis.
Antiepileptic drugs are all considered compatible with breastfeeding.
Regarding lithium, studies show quite variable passage into the breastmilk with an average relative infant dose of about 14%. So, it’s a little bit higher than what we said was the 5% to 10% ratio that most people consider compatible with breastfeeding. But remember that it’s still much lower than placental transfer. So, if a woman has been on lithium during pregnancy, the amount the baby will be exposed to afterward is much lower than during pregnancy.
Drugs and lactation database: (LactMed). (2006). National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/?report=reader
Mother to Baby. (2021, February 2). http://www.mothertobaby.org/.
Reprotox. (n.d.). https://reprotox.org/.
Begg, E. J., Duffull, S. B., Hackett, L. P., & Ilett, K. F. (2002). Studying drugs in human milk: Time to unify the approach. Journal of Human Lactation, 18(4), 323-332.
Poels, E. M., Bijma, H. H., Galbally, M., & Bergink, V. (2018). Lithium during pregnancy and after delivery: A review. International Journal of Bipolar Disorders, 6(1).
Pacchiarotti, I., León-Caballero, J., Murru, A., Verdolini, N., Furio, M. A., Pancheri, C., Valentí, M., Samalin, L., Roigé, E. S., González-Pinto, A., Montes, J. M., Benabarre, A., Crespo, J. M., De Dios Perrino, C., Goikolea, J. M., Gutiérrez-Rojas, L., Carvalho, A. F., & Vieta, E. (2016). Mood stabilizers and antipsychotics during breastfeeding: Focus on bipolar disorder. European Neuropsychopharmacology, 26(10), 1562-1578.