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Question:Breastfeeding and maternal SSRI use: is it safe?
Answer: Depression is becoming one of the major health issues of our time. Young women have significant rates of depression, and pregnancy and the post-partum period are very high-risk times for depression. The SSRIs (selective serotonin reuptake inhibitors) have become the first-line treatment for depressive disorders in women. These facts, combined with the higher rates of breastfeeding in the last decade have made the safety profile of SSRI use in breastfeeding a hot topic.
The numerous benefits of breastfeeding to both mother and baby require us to use caution in our recommendations about the infant effects of maternal medication. There are increasing amounts of data about the levels of these medications in mothers milk and breastfeeding infants. We have some good information about the safety of these medications in terms of observable effects in infants. However, there is little information about the neurodevelopmental effects in babies, and almost no data about long-term effects in children (such as a predisposition to depression) who were exposed to these medications in utero or through breastfeeding. What follows is a brief discussion of the milk and infant levels of SSRIs, observed side effects and our current recommendations.
Dr. Phil Anderson of UCSD's Drug Information Service recommends that we look at how much medication the infant is exposed to by calculating the weight adjusted percent of maternal dosage; milk to plasma ratios just don't tell you how much the baby may actually get. The weight adjusted percent maternal dosage is equal to infant daily dosage (mg/kg) / mat daily dosage (mg/kg) x 100. Keep in mind that there are several variables here: how much medication the mother takes, how much the mother weighs, how much medication is excreted into her milk, the characteristics of drug concentration in her milk (hindmilk often has more drug due to its higher fat content), how much milk the baby takes, how much he weighs, how old he is, etc. Even when infants have a low or undetectable level, we know that there is medication in the milk and that the baby is exposed. We don't know if there will be subtle effects on susceptible organs such as the central nervous system.
It is generally felt that if the wt adjusted % maternal dosage is less than 10% this is an acceptable level of exposure, unlikely to cause side effects. Dr. Anderson also has data (about to be published in Clinical Pediatrics) to suggest that of infant adverse reactions to medications in breastmilk, 79% occur in the first 2 months of breastfeeding, and 97% in the first 6 months of breastfeeding. Also, remember that any time the mother has been taking a medication during her pregnancy, the infant's exposure is much greater in utero than during breastfeeding.
Here are the average wt adjusted % of maternal doses for our common antidepressants:
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| Antidepressant |
Trade |
Wt adj. % mat dose |
Use during BF OK? |
| Fluoxetine |
Prozac |
6.5% |
Least desirable SSRI |
| Bupropion |
Wellbutrin |
<3.0% |
Probably OK |
| Citalopram |
Celexa |
4.4% |
Probably OK |
| Nefazodone |
Serzone |
<1.0% |
Probably OK |
| Paroxetine |
Paxil |
2.0% |
Preferred |
| Sertraline |
Zoloft |
1.8% |
Preferred |
| Venlafaxine |
Effexor |
4.6% |
Probably OK |
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Some recent studies on the subject confirm the above information, and give us more information about low infant levels and the safety of these medications in the post-partum period. In 2001 Epperson et al. looked at the effect of sertraline on breastfeeding mothers by checking platelet levels of serotonin (a measure of transporter blockade to assess medication effect). The mothers had marked declines in their platelet serotonin levels, but the infants had little or no change during breastfeeding. Blood levels in the infants (who had been breastfed for 6-16 weeks of medication administration of the mothers) had low or undetectable blood levels of the sertraline. Ilett et al. in 2002 checked mother's milk and baby levels in mothers taking venlafaxine. Milk levels were 2.5-2.7x maternal serum levels, but the weight-adjusted % of maternal dosage was only 6.5%. There were no adverse infant effects noted. A recent paper by Heikkinen et al. reviewed their experience with citalopram.
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They looked at 11 mother-baby pairs. At delivery the infants had approximately 60% of their mothers' blood level. Milk concentrations were 2-3x higher than maternal blood levels, but the infant blood levels were very low or undetectable. In 2001, Hendrick et al. at UCLA, looked at 50 mother-baby pairs taking paroxetine, fluvoxamine or sertraline. The infants exposed to paroxetine and fluvoxamine had undetectable levels. Of the infants whose mothers took sertraline, only 24% had detectable levels, and these tended to be mothers taking more than 100 mg/day. No adverse effects were noted in any of the study infants. Paroxetine has also been shown to have variable amounts excreted into breastmilk, and undetectable levels in infants. Stowe et al. in 2000 nicely documented variability in breastmilk concentrations from the foremilk (lower levels) to the hindmilk (higher levels).
Fluoxetine, on the other hand is known to be a problem. It has an extremely long half-life, higher milk levels, and there have been reports of infant toxicity. Infant colic, GI symptoms, a seizure-like episode and poor weight gain have all been reported (Chambers et al., 1999). However, most of the infants do well. What is important to remember is that each mother is different; some excrete as little as 3% of the fluoxetine dose in their milk and others as much as 12%. Furthermore, if a mother has been on fluoxetine throughout her pregnancy, the post-partum period is probably not the time to make a medication change. We would recommend that these children be watched closely for adverse effects and weight gain.
In summary, most SSRIs are felt to be safe to use during pregnancy and breastfeeding. Sertraline and paroxetine are the safest due to
low milk levels, and lack of reported side effects in the infant. Fluoxetine is probably best avoided if possible, but we don't recommend changing maternal medication during the vulnerable post-partum period. Close follow up of mothers and babies is important due to variations in maternal dose, milk levels, baby intake and baby sensitivity. There are still many unknowns, and health providers need to take the time to counsel families about the risk-to-benefit ratio of taking needed medication while breastfeeding.
References:
- Chambers, C.D., Anderson, P.O., Thomas, R.G., Dick, L.M., Felix, R.J., Johnson, K.A., Jones, K.L., (1999). Weight gain in infants breastfed by mothers who take fluoxetine. Pediatrics; 104 (5), e61.
- Epperson, N., Czarkowski, K.A., Ward-O'Brien, D., Weiss, E., Gueorguieva, R., Jatlow, P., Anderson, G.M., (2001). Maternal sertraline treatment and serotonin transport in breastfeeding mother-infant pairs. Am J Psychiatry; 158 (10), 1631-7.
- Heikkinen, T., Ekblad, U., Kero, P., Ekblad, S., Laine, K., (2002). Citalopram in pregnancy and lactation. Clin Pharmacol Ther; 72 (2), 184-91.
- Hendrick, V., Fukuchi, A., Altshuler, L., Widawski, M., Wertheimer, A., Brunhuber, M.V., (2001). Use of sertraline, paroxetine, and fluvoxamine by nursing women. The British Journal of Psychiatry; 179, 163-6.
- Ilett, K.F., Kristensen, J.H., Hackett, L.P., Paech, M., Kohan, R., Rampon, J., (2002). Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants. Br J Clin Pharmacol; 53 (1), 17-22.
- Stowe, Z.N., Cohen, L.S., Hostetter, A., Ritchie, J.C., Owens, M.J., Nemeroff, C.B., (2000). Paroxetine in human breastmilk and nursing infants. Am J Psychiatry; 157, 185-9.
Lisa Stellwagen, MD, trained in general pediatrics at Mass General Hospital, fulfilled a National health service corps obligation in Ramona, and then was in private practice in Vista for 7 years. She was also the medical director of the level 1&2 nurseries (96-99) in Boston and has been the medical director of the newborn service at UCSD for 2 years.
Written with the assistance of: Phil Anderson, Pharm.D. (UCSD Drug Information Service), & Eyla Boies, MD (Medical Director of UCSD Lactation Taskforce).
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