Ketamine and Esketamine Safety During Breastfeeding: Systematic Review Insights

Systematic Review Sheds Light on Ketamine and Esketamine Use in Breastfeeding

A systematic review published on October 9, 2026 (OpenAlex W7220949603) compiles and analyzes available data on the safety of ketamine and esketamine use during breastfeeding. This review addresses a critical knowledge gap for clinicians and researchers, focusing on pharmacokinetics—how the drugs are metabolized and transferred to breast milk—and infant outcomes following maternal exposure. The review does not introduce new clinical trial data but synthesizes existing human studies to inform clinical practice and future research priorities.

Pharmacokinetics and Mechanisms of Exposure in Lactation

Ketamine and its S-enantiomer, esketamine, are dissociative anesthetics increasingly investigated for treatment-resistant depression and other neuropsychiatric conditions. Both compounds are known to cross the blood-brain barrier and, by extension, may transfer into breast milk. The review finds that available pharmacokinetic data are limited and primarily derived from case reports or small cohort studies. Measured concentrations of ketamine or esketamine in breast milk tend to be low, but the timing of dosing relative to breastfeeding and individual metabolic differences can significantly affect infant exposure. The review highlights that infant plasma levels, when measured, are typically undetectable or very low, but these findings are based on sparse data.

Infant Outcomes and Clinical Context

Current evidence suggests that short-term infant outcomes following maternal ketamine or esketamine use during breastfeeding are generally benign, with no consistent reports of acute toxicity or developmental harm. However, the review emphasizes that most studies involve single or short-term exposures, such as perioperative use, rather than chronic administration for psychiatric indications. There is a notable absence of long-term neurodevelopmental follow-up data, and the diversity of study designs complicates direct comparisons. The review also notes that existing guidelines from agencies such as the U.S. Food and Drug Administration (FDA) and the American Academy of Pediatrics (AAP) classify ketamine as a substance to be used with caution during lactation, reflecting these uncertainties.

Policy, Research Implications, and Clinical Decision-Making

The systematic review underscores the urgent need for robust, prospective studies on the safety of ketamine and esketamine during breastfeeding, especially as off-label and investigational use expands in mental health care. Regulatory agencies and professional societies may use these findings to update risk assessments and inform clinical guidelines. For prescribers, the review suggests a cautious, individualized approach: weighing maternal mental health needs against potential, but largely unquantified, infant risks. Notably, the review identifies a real-world failure mode: many existing pharmacovigilance systems do not systematically track lactation outcomes in mothers treated with psychedelics, leading to persistent data gaps even as clinical use grows.

Risks, Unknowns, and the Path Forward

While available data do not indicate acute harm to breastfed infants, the absence of long-term safety data and the variability in dosing regimens present significant unknowns. The review warns that extrapolating from single-dose or perioperative exposures to chronic psychiatric treatment is not evidence-based. Researchers are encouraged to design studies that include lactating participants, with careful monitoring of both maternal and infant outcomes. Clinicians are advised to document exposures and outcomes in registries where possible, contributing to a more robust evidence base for future policy and practice.

Conclusion: Balancing Maternal and Infant Health in a Rapidly Evolving Field

This systematic review provides a timely synthesis of what is—and is not—known about ketamine and esketamine use during breastfeeding. As clinical and research interest in these compounds expands, the findings highlight the need for targeted data collection and nuanced clinical decision-making. For now, the lack of definitive evidence means that risk-benefit assessments must be individualized, and both researchers and regulators should prioritize filling these evidence gaps to support safe, effective care for mothers and infants.

How we research: This article was written and reviewed by Dr. Alex Morgan, MD, PhD (psychiatry, perinatal pharmacology), on 2026-10-12. Primary source: OpenAlex systematic review W7220949603.