Abstract / Summary
Ketamine is used in anaesthesia and analgesia, and esketamine nasal spray is licensed as a rapidly acting treatment for treatment-resistant depression; both uses overlap with the postpartum period. We synthesised human evidence on transfer into milk, infant exposure, infant outcomes and breastfeeding outcomes.
The review was registered in PROSPERO (CRD420261364557) and reported according to PRISMA 2020. Databases and registers were searched from inception in January 2026; supplementary sources and citation searching were completed on 21 August 2026. Eligible primary human reports measured drug or metabolite concentrations in human milk, outcomes in breastfed infants, or lactation outcomes after postpartum exposure. Certainty was rated with GRADE principles separately for each of these questions and for infant systemic exposure. Pooling was not undertaken because the studies were not comparable.
Sixteen reports were included. Three provided milk pharmacokinetic data from nine participants, all exposed to racemic ketamine; ketamine relative infant doses ranged from 0.34% to 0.77% and norketamine from 0.29% to 0.95%. No study measured infant plasma concentrations or long-term neurodevelopment. Perioperative studies showed no consistent adverse breastfeeding signal, but these secondary outcomes reflect maternal recovery and carry no information on infant exposure. No study quantified exposure during repeated intranasal esketamine.
Transfer of single or intermittent racemic ketamine into mature milk is below the conventional 10% threshold with moderate certainty, whereas certainty on infant systemic exposure and infant outcomes is very low. The findings do not cover chronic treatment and cannot be extrapolated to repeated intranasal esketamine.