Zuranolone and Breastfeeding: Emerging Data and Clinical Implications

Zuranolone is a novel treatment FDA-approved for the treatment of postpartum depression: an oral neuroactive steroid and positive allosteric modulator GABA-A receptors. Approved for adults with postpartum depression in the United States, it represents an important advance for rapid symptom relief. However, since 83% of postpartum individuals in the United States initiate breastfeeding and 60% continue for at least six months, information regarding the safety of antidepressants during antidepressants is essential. Despite excitement about zuranolone, current manufacturer recommendations advise suspension of breastfeeding during treatment. In our clinical practice, this limitation is often a deal breaker. Breastfeeding mothers with PPD will instead opt for treatment with traditional selective serotonin reuptake inhibitor (SSRI) antidepressants, a class of medications which have well-established safety data in lactation. Zuranolone Transfer into Breast Milk A phase 1 open-label study evaluated zuranolone transfer into breast milk. A total of 15 healthy, nonpregnant, lactating individuals received 30mg daily for five days. The mean relative infant dose (RID, or the weight-adjusted percentage of the maternal dose ingested by an infant) was 0.357% at a maternal dose of 30mg. A 50mg dose produced an estimated RID of 0.984%. In general, an RID under 10% is considered compatible with breastfeeding, and the measured values for zuranolone taken at standard doses were under 1% and comparable to or lower than many SSRIs. Notably, breast milk concentrations of zuranolone were below quantifiable levels 4 to 6 days after the last dose. Impact on Milk Production In this report, women experienced, on average, an 8.3% reduction in breast milk volume; however, the authors note that this was likely unrelated to zuranolone and could be attributed to other factors such as (lack of) infant demand and maternal stress. Effects of Infant Exposure to Zuranolone in Breast Milk There are, however, no published articles systematically studying and detailing the effects of zuranolone on breastfed infants or on long-term milk production. In an outpatient clinic, Price and colleagues reported on their real-world experience with zuranolone in a cohort of patients including 25 nursing infants. Notably, they found zuranolone was well tolerated and did not observe sedation or any other side effects in the nursing infants exposed to zuranolone via breast milk. Although this emerging clinical data is reassuring, the authors emphasize that ongoing, careful monitoring remains important, given the small sample size and lack of published prospective studies. Ideally, we would like to have a study that systematically assesses the amount of zuranolone detected in the infant’s serum and uses standard rating scales to monitor sleep, feeding patterns, and behavior. Guidance for Clinicians In practice, the lack of robust safety data remains a barrier for prescribing zuranolone to patients who are breastfeeding. While some centers have observed good tolerability in a small number of nursing infants, caution is required in the absence of systematic studies and detailed published data on zuranolone exposures in nursing infants. While available pharmacokinetic data suggest that infant exposure to zuranolone via breast milk is low, clinical vigilance remains essential, particularly during the critical early months of life. Newborns and preterm infants are at a higher risk for adverse drug effects due to their immature hepatic and renal function, limited ability to metabolize medications, and greater neurological vulnerability. If zuranolone is necessary for treatment of PPD in the mother, its use may not be a reason to discontinue breastfeeding; however, at least for now, we would recommend pumping to maintain milk supply and discarding breast milk during the 14-day course of treatment with zuranolone. Ruta Nonacs, MD PhD References: Deligiannidis KM, Bullock A, Nandy I, Dunbar J, Lasser R, Witte M, Leclair B, Wald J. Zuranolone Concentrations in the Breast Milk of Healthy, Lactating Individuals: Results From a Phase 1 Open-Label Study. J Clin Psychopharmacol. 2024 Jul-Aug 01;44(4):337-344.