There’s nothing like a close friend suffering psychiatric difficulties to motivate a psychiatrist to do some serious reading. Recently, your humble editor encountered this situation.

The patient is a young woman with no psychiatric history who noted more than a normal amount of anxiety after the birth of her child. She found herself worrying constantly about her child’s welfare, which interfered with her already limited amount of sleep, leading to daytime fatigue and increasing demoralization. She sought formal psychiatric consultation, was prescribed Celexa and Ativan, and was given a fair amount of complicated information about risks vs. benefits of medication while breast-feeding.

Her dilemma (and the dilemma of the millions of women who suffer postpartum depression or anxiety every year) was that, on the one hand, she wanted to breast-feed, because of the well known benefits. These include bonding between mother and infant, some measure of protection against infections, and possibly some benefit in terms of the child’s cognitive development in subsequent years. On the other hand, she was concerned about the possible detrimental effects on her infant of exposure to medication.

So what should she do?

In making decisions about the safety of breast-feeding on psychiatric medication, we’ve come a long way since 1996, when the first critical review of antidepressants during breast-feeding was published in the American Journal of Psychiatry (1). At that time, only 15 published reports were located on the topic; the most recent review, in the same journal in 2001 (2), cited 44 such studies, and much important research has been reported since then.

Before reviewing these findings, here are two helpful pearls on newborn physiology. First, newborns metabolize drugs slowly, because their cytochrome P-450 activity is about half that of adults. This effect is even more pronounced in preterm babies, who are likely to be at much higher risk of toxic exposure if the mother is breast-feeding while taking medications. The good news is that after the first two months of life, a baby’s liver gets revved up, to the point that it can metabolize drugs two or three times faster than adults. So, all things being equal, it’s better for a new mother to wait a couple of months before beginning meds.

A second point is that the infant blood-brain barrier is less mature than in adults, meaning that CNS meds tend to concentrate in the infant brain much more so than in the adult brain. This effect is amplified by the fact that infants have very little fat, and thus have fewer “parking places” for lipophilic drugs (which include all SSRIs) to hang out, other than the brain. Why is this especially relevant? Because even though breast-fed infants have miniscule blood levels of antidepressants, there may be higher levels hidden from the assay in the CNS.

With that as background, here are the most clinically relevant findings to have emerged over the past several years:

1. Unfortunately, it is now clearer than ever that any medication that mom ingests will find its way into breast milk, and thus, ultimately, into the baby. While this may seem obvious to many, it was not demonstrated for some SSRIs until quite recently.

2. Among the SSRIs, the amount of drug that has been quantified in infant serum has been exceedingly low, to the point of being undetectable. For example, one of the most rigorous studies was conducted by Stowe and colleagues who measured levels of Paxil in breast milk and in the serum of nurslings (3). Using high performance liquid chromotography, no paroxetine was detected in any of the 16 infants studied, meaning that their levels were less than 2 nanograms per ml. For those rusty on their chemistry, this means less than 2 millionths of a gram per mililiter. There have been similar findings for Celexa, Zoloft, and Luvox. The exception to this trend is Prozac, which, because of its long half-life and the long half-life of its metabolite, has been detected in significant quantities in infants. For example, one case reported nursling serum levels of 340 ng/ml of fluoxetine and 208 ng/ml of norfluoxetine—significantly higher than the levels documented in the mother’s breast milk.

3. Well documented adverse events in exposed infants have been exceedingly rare, with two exceptions: Prozac and doxepin. In the recent American Journal review (2), 10 of 190 fluoxetine-exposed babies showed adverse events such as irritability and colic vs. 0 of 93 infants exposed to other SSRIs (mostly Zoloft and Paxil). Of course, Prozac has been around the longest, and has been used the most in breast-feeding women, so this higher incidence of Prozac-related problems may be partly artifactual. On the plus side for Prozac, the only study to have looked at long-term outcome of exposed infants was done with Prozac, and found that 4 exposed infants were developmentally normal at 1 year of age (4).

4. Zoloft is the only antidepressant that shows a clear time course between ingestion and high peak levels in breast milk (5). This means that it makes sense for mothers to pump and discard a feeding 7-10 hours after their dose of Zoloft, when the breast milk level peaks. Doing this will reduce an infant’s overall exposure to medication by about 25%, assuming that feedings occur about every 3 hours.

5. There is almost no useful information available on benzodiazepine safety in breast-feeding. There has been one reported case of persistent cyanosis in an infant exposed to Klonipin (this infant was fine by day 10), and one case of lethargy and weight loss in a Valiumexposed infant. Small case series of exposure with shorter half-life benzodiazepines have not reported any adverse events, leading to the usual practice of choosing shorter-acting meds such as Ativan when anxiety needs treatment. But not too short-acting: one case of xanax withdrawal in an infant has been reported.

The upshot? All of the SSRI’s except for Prozac appear to be quite safe in breast-feeding. This is good news for mothers and their babies.

 

TCR VERDICT: SSRIs in Breastfeeding? Fine…except for Prozac!

 

References

1. Wisner KL, Perel JM, and Findling RL: Antidepressant treatment during breast-feeding. Am J Psychiatry 1996; 153:1132-1137. 2. Burt VK, Suri R, Altshuler L: The use of psychotropic medications during breastfeeding. Am J Psychiatry 2001; 158:1001-1009.

3. Stowe ZN, Cohen LS, Hostetter A, et al: Paroxetine in human breast milk and nursing infants. Am J Psychiatry 2000; 157:185-189.

4.Yoshida K, Smith B, Craggs M, et al: Fluoxetine in breast milk and developmental outcome of breastfed infants. Br J Psychiatry 1998; 172:175-178.

5. Stowe ZN, Owens MJ, Landry JC, et al: Sertraline and desmethylsertraline in human breast milk and nursing infants. Am J Psychiatry 1997; 154:1255-1260.


 

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This article was published in print 5/2003 in Volume:Issue 1:5.