Drs. Stowe and Owens Reply

To the Editor: We appreciate the acknowledgment of the detail provided in our earlier manuscript and share the concern raised about the unknown sequelae of infant antidepressant exposure during breast-feeding (1). The focus of the study was not to demonstrate that sertraline does or does not have an impact on nursing infants, but rather to provide some scientifically derived mechanism for minimizing infant exposure to the medication. Previous studies have reported that the milk-plasma ratio is a method of determining infant exposure (1). This method, laden with the potential confounds of aliquot of breast milk (gradient) and time after dose (time course), does not provide a method for reducing infant daily dose. Determination of the time course allows the clinician and patient to reduce infant dose of sertraline up to 24% by discarding a single breast-feeding. It also provides a medication-specific formula, currently not available for any other medication, for calculating, not estimating, the maximum infant daily dose. Defining the exposure provides the basis for future infant follow-up studies in assessing “cause and effect.” Until detailed follow-up studies have been completed, we feel that every effort should be made to minimize infant exposure to medications while maintaining maternal mental health.

Epperson and colleagues made a significant contribution in assessing the potential effects of sertraline exposure in nursing infants (2). This group would have been surprised to see any effects on peripheral measures of serotonin beyond population variation with a maximum calculated infant daily dose of 0.124 mg per day of sertraline (pair 11). We are cautious about the reliability of peripheral markers to determine whether or not a medication has an effect in an infant because the possibility exists for rapid sequestering in lipophilic tissue, such as the brain, without measurable peripheral effects beyond the standard deviation. The emphasis on serotonin is warranted on the basis of the selectivity of the newer agents, yet these medications can affect other neurotransmitter systems as well. This is particularly true for the tricyclic antidepressants.

Perhaps, the terminology in the letter could be revisited, since sometimes this terminology becomes confusing in the literature about medications in breast-feeding. Terms such as “undetectable,” “negligible exposure,” “no significant exposure,” and “harmless” are misleading, and we must remember that the infant is exposed whether or not we can detect the medication or measure an effect. We do not think that we will ever be in a position to state that a medication is “safe or harmless” in either pregnancy or lactation; this is a relative determination for each individual. Further, we think that we need to be mindful not to apply these terms—ensuring that a comprehensive risk/benefit assessment is completed on a case by case basis.