Is Ketamine Safe for Breastfeeding Women?
I am taking care of a patient with a history of severe recurrent depression. Although she did relatively well during pregnancy on duloxetine 120 mg, she experienced recurrent, severe depressive symptoms after giving birth.
She has responded well to IV ketamine in the past. Can this treatment be used if she is breastfeeding?
Here's What We Know About Ketamine and Breastfeeding
Ketamine has been used as a general anesthetic for over 50 years, and more recently has been used for the treatment of depression, especially in individuals with severe or treatment-refractory depression. The use of ketamine for the treatment of postpartum depression has been considered but there is inadequate data regarding its effectiveness in this setting. While ketamine may present certain advantages, including its rapid onset of action, what do we know about its use in breastfeeding women?
Ketamine is metabolized to norketamine, dehydronorketamine and hydroxynorketamine. Pharmacokinetic studies have indicated that ketamine is rapidly metabolized and cleared from the bloodstream. After a single IV infusion of ketamine, peak levels of ketamine and its major metabolites in the blood peak at 3-4 hours.
We have less information regarding the pharmacokinetics of ketamine in breastfeeding women. In general, peak levels of medications in breast milk closely parallel levels measured in blood. In a study including four lactating women who received intramuscular ketamine, peak levels of ketamine and its metabolites were observed between 3 and 4 hours after dosing (Wolfson et al, 2022).
In this study, the relative infant dose (RID), defined as the infant’s daily dose divided by the mother’s daily dose (mg/kg/day) × 100, was calculated to be 0.650% for ketamine at 0.5 mg/kg and 0.766% for ketamine at 1 mg/kg. A RID of less than 10% is generally considered acceptable.
No studies have assessed ketamine blood levels in nursing infants. One retrospective chart review assessed 298 breastfeeding infants whose mothers had received ketamine tubal ligation surgery and noted no weight loss in infants. Further studies are needed to better characterize the impact of ketamine, if any, on breastfeeding infants.
While the information is limited, it is generally reassuring, with a small pharmacokinetic study demonstrating low and rapidly declining levels of ketamine and its metabolites in breast milk during the 12 hours after dosing. Based on these findings, Wolfson and colleagues speculate that it is unlikely that the nursing infant would experience clinically relevant symptoms as a result of ketamine ingested in the breast milk. In addition, oral bioavailability of ketamine is considerably lower than ketamine administered intravenously or intramuscularly.
Given the limited data, ketamine should be used with careful infant monitoring for sedation and poor feeding. Avoiding breastfeeding for 6 to 12 hours after a single dose will markedly decrease infant exposure to the drug in milk.
Ruta Nonacs, MD PhD
Ketamine – Drugs and Lactation Database (LactMed®)
Wolfson P, Cole R, Lynch K, Yun C, Wallach J, Andries J, Whippo M. The Pharmacokinetics of Ketamine in the Breast Milk of Lactating Women: Quantification of Ketamine and Metabolites. J Psychoactive Drugs. 2022 Jul 26:1-5.
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