Please take a moment to complete this brief pretest. While taking the pretest is optional, your answers will help us determine whether the content provided in this presentation either mirrors or enhances your knowledge of this particular postpartum depression topic.

Physician Program: To take the pretest, please click here.

Nurse Program: To take the pretest, please click here.

Social Worker Program: To take the pretest, please click here.

Taking Antidepressants While Breastfeeding: Duration, Risks, and Long-Term Effects

Presenter & Moderator: Ruth A. Lawrence, MD, FAAP, FAACT, FABM
Panel: Katherine L. Wisner, MD, MS; Debra Bogen, MD, FAAP; Laura Miller, MD






Slide 1. I think the introduction of this topic was an invitation to escape, so for those of you who remained, thank you very much!




Slide 2. We did of course do the usual objectives, and hopefully we will fulfill all those objectives.




Slide 3. One of my main objectives is to remind all of you of the compelling reasons to breastfeed. Breastfeeding is a health goal of the United States, the goal having been set way back in 1978 -- not achieved yet -- and it’s similar to the health goal of decreasing hypertension, obesity, and stopping smoking; but increasing breastfeeding. We just finished a 3-year national campaign to the public to encourage breastfeeding, and it was based on the risks of not breastfeeding. The tag line was: Babies are born to breastfeed. These 6 items are the main reasons why a mother would breastfeed her baby. Actually the first reason is the only one you need: species specificity. Human milk is made for the human infant. And for all of its needs, whether it’s brain growth or general growth or protection or whatever it is, we’ve heard a lot about the impact of human milk on brain growth in recent years, starting with the work of Alan Lucas in London on a group of prematures where he gave mothers milk by feeding tube to remove the impact of the mother nursing the baby and compared it with infant formula, and showed that in 7-8 years, the children had a 10-point advantage on the Wechsler scale. Many other studies have shown the advantage in development, auditory and visual acuity for those who receive human milk. Why?




Slide 4. Probably because human milk contains cholesterol; formula doesn’t contain any cholesterol. Taurine is an amino acid specific to human milk, and of course DHA (docosahexaenoic acid); you’ve heard a lot about DHA. The formula companies are now dumping DHA into their formula, trying to close the gap with human milk.




Slide 5. We know the psychological and cognitive benefits as well. These were studied over 30 years ago by Niles Newton, and the infection protection qualities of human milk will probably be the best documented, because in developing countries the death rate in the first year of life for children who are not breastfed is 50%.




Slide 6. Human milk is protective, and even in the United States, it’s protective against diarrhea and respiratory infection, otitis media, pneumonia, urinary tract infection, necrotizing enterocolitis (which is one of the great fears in the neonatal intensive care unit among prematures), and any invasive bacterial infection.




Slide 7. We also have very good data on the protective effects against some chronic diseases in childhood. Work done on the 10-year perinatal follow-up study showed that children who were breastfed for at least 4 months have a reduced risk of childhood cancers in the first 10 years of life, a reduced risk of Crohn’s disease, celiac disease, and diabetes. In Scandinavia, they saw an inordinate rise in childhood-onset diabetes, and noted at the same time a drift downward in the incidence of breastfeeding. When they did a prospective study in Finland on 10,000 children, they were able to demonstrate that if children were breast fed for at least 4 months, it reduced the onset of childhood diabetes. And as you know, this is almost a pandemic in the United States as well, so it’s another one of the great reasons to consider providing human milk for the infant.




Slide 8. We know that when there’s a decrease in illness, it decreases clinic visits, there is a decrease in the severity of the illness, which decreases hospitalizations, and decreases the need for medical care.




Slide 9. And it decreases the cost.




Slide 10. Most people forget that there are benefits to breastfeeding for the mother, and here are a few. First, it improves postpartum recovery; there is less blood loss. The uterus returns to normal more quickly. The other events around the postpartum period are much more physiologic. As we like to say: It’s not nice to fool Mother Nature! She thought you were going to breastfeed! There are psychological benefits. The feeling of empowerment; of being able to feed this baby, and have this baby grow just on what you can provide. A decreased risk of osteoporosis in the long range: that seems a little counterintuitive, but studies have shown that for women who breastfeed, after they have weaned, their bone densities are much improved over their prepregnancy levels, and this is true in long-range studies for women 70 and 80 years old; the lowest incidence of osteoporosis is among those who breastfed. The next highest incidence is among those who at least had a pregnancy. The highest risk is among those women who have never been pregnant and never lactated. There is a reduced risk of premenopausal breast cancer and ovarian cancer, if mothers have breastfed, and a reduced incidence of pregnancy-initiated long-term obesity. Many women are very svelte until they have their first baby. And if they don’t breastfeed, they never get rid of that baby fat. This can herald the onset of obesity for many women in this country, and obesity, of course, is a major health dilemma today.




Slide 11. Well, you always have to ask the question: Is the pressure to breastfeed a dilemma for the 10% or 15% of women who may be vulnerable to postpartum depression?




Slide 12. I would always be very alarmed if a mother suddenly weaned, because in the rare cases of child infanticide and child abuse in mothers who have been lactating, a sudden weaning -- and when the physician intervenes and says: Well, I’m going to give you a terrible drug, so stop breastfeeding today -- that’ll precipitate a psychiatric crisis. So it’s not recommended.




Slide 13. But one of the issues is the pharmacology of postpartum depression; the drugs that one has to use.




Slide 14. It’s the risk/benefit ratio. We’ve already heard about the tremendous benefit of being breastfed. What is the risk of this particular medication to the baby? Particularly, you would select the drug so it is as benign as possible, and as effective as possible for the mother.




Slide 15. Well, this isn’t just hocus pocus; we do have information. There are pitifully few specific clinical studies on given drugs and given clinical situations, but we know a lot about the pharmacology. We know about the properties of the drugs; we know about the plasma/milk ratios. What we always need to consider is the infant; it’s very different than just considering the drug for the mother. Can the infant absorb the drug? If this is a medication that’s poorly absorbed in the gut or poorly absorbed with food, the baby isn’t going to absorb it very much. Can the baby detoxify it? Can the baby excrete it? So you never can answer the question unless you know the age and the maturity of the baby. Just looking it up in the book and taking somebody’s word about the drug is not adequate. Most of the time, when you know the age of the baby and those properties, it turns out to be safer.




Slide 16. And it makes a difference in the route of administration. Most of the time we’re talking about ambulatory women who are taking their medications by mouth, but sometimes they’re given intravenously or intramuscularly, and now that the transdermal delivery system has become very common, I’m sure many of the medications you use will soon be available as a patch. What you’re looking for is a steady state; a patch is good for that.




Slide 17. So the drug characteristics that we look at are the absorption rate, the half-life, and the peak plasma time. The half-life gives us an idea of how long it’ll take to clear a particular drug because 5 times the half-life will totally clear the drug. If you have a half-life of 7 days, 5 times that is 35 days, so we’re not going to be clearing most of these medications, but we will be assuming a steady state. And when you’ve done that, when you medicate the mother maybe once a day, she will have a peak plasma time and then return to steady state. Well, let’s not breastfeed at peak plasma time. Time the dosing around the feeding so that the baby at least avoids that peak. So there are ways that we can modify things.

Volume distribution is another drug characteristic that we rely on quite heavily. Volume distribution essentially says: When the drug enters the body, where does it go? Does it stay in the plasma? Does it distribute everywhere? A drug with a large volume of distribution hasn’t much left in the plasma, hasn’t much left to get in the breast milk. Most of the medications that you will be using -- the SSRIs (selective serotonin reuptake inhibitors) -- all have very large volumes of distribution, so that even though we don’t have the study per se or the milk volumes, we know these drugs will not be in high levels in the milk. The dissociation constants, too, are a very important factor; that’s a very fancy way of saying: What was the pH?




Slide 18. And then of course the size of the molecule; there are some molecules like insulin and heparin and a number of others that are so big, they don’t pass into the milk. The degree of ionization and the pH: you notice that plasma has a pH of 7.4, but human milk has a pH of 6.8, so that it’s slightly acidic. One also needs to know the solubility in water, and the solubility in lipids of a given drug, as well as the protein binding. Is it all bound up in the plasma and won’t reach the milk?




Slide 19. Pharmacologists like to look at drugs in a scheme like this, so I thought I’d show it to you, demonstrating the various ways a drug can get into the body; it all ends up in the blood stream and is either bound or unbound to albumin. And then it’s distributed to various tissues; the liver will metabolize it. Does it go to the brain? Is it excreted by the kidney? And in this diagram, the breast is a portal of excretion. Some is deposited in the bone, and some is deposited in the fat like some of the environmental toxins we worry about. So in the end, the drug is either stored or excreted.




Slide 20. An example of one of the things you can do when you’re trying to select a medication that will be safest during lactation, is to take the drug that has the lowest milk/plasma ratio -- this is the family of sulfa drugs. We don’t use them very much anymore, but I keep this slide because it’s such a good demonstration of the fact that here’s a whole family of medications that you’d pretty much use for the same purpose. And yet the one at the top of the column, sulfacetamide, has a milk/plasma ratio of 0.08. You work down through the family and sulfanilamide has a milk/plasma ratio of 1.0, which means there’s just as much in the milk as there is in the plasma. Well, if you can take your choice, you’re going to take the one at the top of the column.




Slide 21. And we know that high lipid solubility means that the ratio between milk and plasma is pretty nearly 1.0. Small molecules cross the membrane, if you remember your osmosis studies in sixth grade. But a very important parameter is that weak acids are not attracted into the slightly acidic milk.




Slide 22. And therefore, their milk/plasma ratios are always under 1.0, whereas weak bases are attracted and go into the milk. So we’ll keep that in mind while we look at some other information.




Slide 23. What about the effect on the nursing infant? Absorption from the gastrointestinal tract: remember, it’s going to be absorbed with food, and then it’s a question whether the infant can detoxify it and excrete it.




Slide 24. So how are we going to minimize the effect of these medications if we accept the premise that these mothers are going to be medicated, and we would like them to continue to breastfeed as long as we can select a drug that is safe for the infant? We try to avoid the long-acting forms of drugs; the reason is that what makes a drug long-acting is slow liver metabolism. If it’s long-acting for 12 hours for an adult, it’s going to be 3 days for a baby. Schedule the dose so the least amount gets into the milk; as we mentioned before, stay with a steady state, and keep away from the peak plasma times. Always watch the infant for any unusual signs or symptoms, and as Dr. Wisner has pointed out in her many wonderful articles, you ought to observe the child prior to medicating the mother so you know what is normal for the child. If the baby is fussy and colicky from 6:00 to 10:00 every night, and then the mother starts taking medication, if the baby is still fussy and colicky from 6:00 to 10:00 every night, that isn’t the fault of the drug. And choose the drug that has the least amount in the milk; in some cases, one may need to pump and discard the milk. When you’re trying to reach a steady state for postpartum depression, it isn’t going to be just a flash of drug here; that is more effective for drugs that you take once or twice or for 2 or 3 days.




Slide 25. We do know that all antidepressants are excreted in the milk, and we do want to observe the infant behavior beforehand. There have been some studies done where nursing mothers have been given the drug, or not given the drug, and then followed for adverse effects on the baby, sometimes even milk and infant levels.




Slide 26. Good studies have been done for a selected group of medications.




Slide 27. In general, under infant levels in multiple studies of fluoxetine --




Slide 28. -- and this is a study of sertraline -- the drug was not detected within the level of detection in the infant’s serum, and there were no adverse effects; this is actually one of the drugs of choice for treating postpartum depression, and it’s usually the one our lactation study center drug center would suggest.




Slide 29. Paroxetine: here’s another one, reflecting a series of studies. In the infants’ serum levels, no drug was detected, and no adverse effects were noted.




Slide 30. Most of the time we don’t recommend a tricyclic antidepressant; however, nortriptyline has been studied, and you will notice that infant serum levels, if they exist, are below the detectable level, and no adverse effects have been noted.




Slide 31. There is a concern for certain antidepressants causing a failure of weight gain in breastfed infants, and probably foremost, fluoxetine has been noted for that. I had a case just the other day where a physician in one of our suburbs medicated the mother with fluoxetine and the baby’s growth curve just went down. And he said: Do you think there’s any correlation? We discussed it for a few minutes and recommended that he change the mother’s medication -- wean her off the fluoxetine and move to sertraline -- which changed the picture entirely.




Slide 32. So inadequate weight gain is seen for some of these medications.




Slide 33. And just to show you what the weight gain looked like, I show this to you just to prove that some good studies have been done.




Slide 34. We don’t know about the short and long-term effects on infants. There have been some short studies, some small studies in which they did not find any impact on development, but until we have 20 years of controlled studies following these medications, I don’t think we can say absolutely that there’s no effect. The good news is that none have been reported so far.




Slide 35. However, there is a very nice study done by Epperson looking at the impact of SSRIs on platelet 5HT (5-hydroxytryptamine) concentrations, and you’ll notice on this graph that the left-hand figure is what happened to the mothers’ levels who were on the SSRIs, which is one of the measurements of the impact of an SSRI. The right-hand graph shows the same measurements in the infant of those mothers who were receiving the medication, and you see it had no effect on their platelet 5HT, which is very reassuring.




Slide 36. So the potential effects are colic and irritability, but this is why it’s so important to observe the child before you start the medication, because some babies are colicky anyway. It could have a sedating effect on the infant. We mentioned weight gain. We do occasionally see withdrawal in the infant when mothers have taken the medication, postpartum. I have never seen a case reported on coma, but if you take enough of anything, it’s certainly a possibility. And then there’s some slight association with one drug or another like colic or something of that nature, but in general, there are very few side effects.




Slide 37. This is just comparing SSRIs with bupropion -- a whole group of them -- and that is another medication that has been looked at.




Slide 38. General Recommendations




Slide 39. Recommendations (cont’d)




Slide 40. Looking at references, I just want to say a word about this, because people often quote the PDR (Physicians' Desk Reference). The PDR can only make statements about use of their drug when they’ve studied that use of the drug. Nowhere in the PDR does it say it’s appropriate to use a medication during lactation, because they haven’t studied it, and they are not going to study it because they’re not going to invest money -- they’d just as soon lose that market as spend money to explore it. And if they don’t explore it, they can’t say anything about it.




Slide 41. So the PDR has never said a drug was good in lactation and it’s almost true for pregnancy, although they’ve done some studies and met the requirements. So the fact that the PDR doesn’t say anything is no testimony, one way or the other. The AAP (American Association of Pediatricians) list is now about 5 years old, so that there are newer drugs and newer preferences. The AAP drug list is very conservative; they don’t say anything they can’t back up, but they have done a magnificent job of reviewing a lot of medications, many of which are not SSRIs but they help us anyway. And it is interesting, of the many other drug lists that are popular and available, they never make a really strong statement unless the AAP already made a strong statement about the safety of that drug.




Slide 42. Decision-Making: Options for Breastfeeding Women




Slide 43. So, a few questions.




Slide 44. If a woman is taking fluoxetine during pregnancy and she wishes to breastfeed while continuing the treatment, when would you prefer to have her blood tested to rule out drug accumulation? In most cases, I don’t think too many people are measuring the levels on the baby unless the baby is showing some effect, is not gaining weight appropriately, or is having many other signs and symptoms.




Slide 45. There are a number of herbals that are presented as doing the same thing as an SSRI. In mild depression, they have done some clinical studies on mothers taking St. John’s wort vs amitriptyline, and for mild depression, apparently the clinical impact was very effective with St. John’s wort. For serious depression, it was not effective. But this brings up the whole issue that you can go down to the local drugstore and buy all the St. John’s wort you want. This is a problem; that many mothers think if you can buy it across the counter, it’s okay; and probably the biggest problem is that they need to have an appropriate diagnosis. I’ve been concerned about when people screen for thyroid disease, because probably the most common disease that presents like depression is thyroid disease. And the most common disease that occurs postpartum is thyroid disease; so that now that you can screen for thyroid disease so easily with just a finger stick of blood, it’s appropriate to screen fairly frequently.




Slide 46. Our breastfeeding and human lactation study center drug call line receives dozens and dozens of calls on these medications. With this question, we might turn to the panel and see what sort of comments they might like to make on any and all of these medications. Dr. Wisner, since you’ve written so much on this subject, maybe you’d like to comment.




Slide 47. Katherine L. Wisner, MD, MS: Well, I actually have a somewhat different first response when I’m asked the question: What is the best drug for a depressed woman to take for postpartum depression if she’s breastfeeding? And my usual response is: The antidepressant that works for her. One of the major issues is you don’t want to pick a theoretical “best drug” for her if the one that works is X; you want to go with X. And there really is, in my opinion, not enough damning information about any one antidepressant to say that’s such a negative choice for breastfeeding that you should use another drug over it. Let’s say fluoxetine -- which is in theory the least desirable drug to use for breastfeeding as Dr. Lawrence points out because it’s got a long half-life, and it’s got an active metabolite with an even longer half-life -- I would have to ask myself: Is the risk of using another drug which then incurs the risk that she’s not going to respond to it, and that the baby might have to wait weeks before we find that out and be exposed to depression, is that worth the difference in theoretical safety? And my response to that is “no.” So if there’s a drug that works, I use that. If there’s no treatment history, there’s no question that I would use or recommend sertraline or paroxetine, or a third choice, nortriptyline, based on exactly the choices that Dr. Lawrence gave. And I probably would use the woman’s individual clinical symptoms and a risk/benefit discussion of each of the drugs and the side effects, and really engage her in that discussion.

That said, there are a number of women who do respond to fluoxetine (Prozac) who have heard negative things about it, who say to me: I understand what you’re saying; if I switch to a different drug, there’s a risk that I might not respond. But, you know, that stuff I heard scares me, so I’m willing to take that risk. So I think the important point is not to get wedded to any one drug, and really maximize the chance that the woman is going to respond and not expose her baby to depression, and use these theoretical parameters when they’re reasonable to do so. In a greater context, I think we’re incredibly lucky to have the amount of data about antidepressants for use in breastfeeding that we do. It’s an entirely different question when you get to drugs used to treat bipolar disorder, which have much greater penetration into breast milk, into the baby, and essentially more toxicity, so we’re actually rather lucky in this arena.

Debra Bogen, MD, FAAP: I’m going to approach this from a pediatrician’s point of view because that’s what I am, so it’s hard to speak about treating women with psychiatric drugs. But my role really as a pediatrician is to recognize if a mom has depression or needs to be referred. But if she already has the diagnosis, to really support her to get treatment. I spend a lot of time talking to moms about the fact that we want them to enjoy their parenting, and that it should be an enjoyable experience, and if they feel miserable inside, they can’t enjoy their parenting experience. They may be a good mother anyway; they may function and feed their baby well, and clothe their baby well and bathe their baby well, but they may not be enjoying that interaction and they’re missing out on a wonderful opportunity. So I try to encourage women to get treatment. That’s sort of my role, and then to give an option for what kind of treatments they want to get.

I do a lot of breastfeeding support in my office, so I tend to see the women who are breastfeeding, and they don’t want to take drugs a lot of the time. It’s a real barrier for them. They just feel like they want to keep it pure; they avoided medications during pregnancy, and they’re going to continue to do that. So I try to give them a balanced point of view. But again, refer them to both options: for cognitive behavioral therapy or for treatment, whatever they want. But again, if they’re not getting better, encourage them to take a medication; that it’s perfectly safe. And I think that’s one thing I can tell women is based on the literature, based on my experience, it’s perfectly safe for them to take antidepressant medications during pregnancy. I don’t prescribe them myself. I don’t think that’s my role, but I do think my role is to support a woman to get better so she can care for her baby and enjoy her baby’s childhood, instead of letting it pass by and then in hindsight say: I wish I had been able to enjoy it more.




Slide 48. Laura Miller, MD: I want to underscore your point about the pressure to breastfeed, in that a number of women who are depressed do get tremendous pleasure out of breastfeeding, and some say that that’s the most pleasurable thing that they do. By contrast, another subset of women finds breastfeeding to be quite stressful and among that subset, there are some who with breastfeeding support can come to experience breastfeeding as something that works very well for them and is very helpful, and others who really just feel pressured and who really need to be let off the hook to say: Well, this is one stress I’m going to take out of my life. Among that subset, it’s also important to underscore that some percentage of those women have been sexually abused as children, and sometimes the breastfeeding can serve as a trigger of memories of early childhood sexual abuse, and can be worked through in a way that’s very therapeutic and empowering. But in other cases, a woman is simply not ready to do that, and again, needs to be let off the hook. So a careful evaluation of the reasons why breastfeeding feels stressful, and whether or not it makes sense to intervene to try to assist the breastfeeding or let the woman off the hook, is really important.

Another thing to underscore is the communication between the pediatrician and the prescribing physician of the mother, and ideally a third part of the triad for support of this endeavor could be identifying a lab which can do serum levels in a baby if and when they become necessary, not as a routine occurrence (not all labs do it). So if one in advance of prescribing establishes communication between the prescribing physician and the pediatrician and has this lab ready, then everything is all set; so that if the baby does indeed experience something that looks not developmentally expected or not expected from that baby’s baseline, then one can get a serum level. If the level is nondetectable, as it frequently is, it’s going to key people in to look for other causes of that whatever-it-is symptom, and not automatically assume that it’s the medication and that the breastfeeding has to abruptly stop.

A third issue I want to underscore is you’re talking about the limitations of looking to the PDR as a source of information about medications during pregnancy and breastfeeding, but then again, if we’re going to point out the limitations, we need an alternative place to look, and one product that we’ve created for the providers that we work with is a chart that is online, and also in printed form, that really runs through each of the commonly used antidepressants and risks and benefits during pregnancy and breastfeeding.




Slide 49. Medication Prescribing Resources




Slide 50. Medication Prescribing Resources (II)




Slide 51. Ruth A. Lawrence, MD, FAAP, FAACT, FABM: One question that’s come to our drug line recently has been that women have called up and said that their physician has told them that because they are depressed, they cannot breastfeed. Now why would one say that?

Dr. Wisner: I sure wouldn’t, but just think about possibilities. There are clinicians who worry about what my colleagues have spoken about in terms of, are symptoms due to breastfeeding?

Dr. Lawrence: This is before they start. This is: You cannot breastfeed, period.

Dr. Wisner: Oh, okay. If it’s before they start, then I would really wonder if it’s because they anticipate that the woman might need a medication, and they’re worried about that; that would be the other possibility. In the 1980s, now 20 years ago, is when I started to look at mother and baby serum levels (then it was nortriptyline), and the reason I did it, I was reminded in Ruth’s talk that there were several women from La Leche League in Pittsburgh, some of whom had postpartum depression, and they asked to meet with me and they came into my office and they said: Some of us have had postpartum depression; women we counsel have postpartum depression, and the pediatricians routinely tell us we can’t take an antidepressant and breastfeed. And we feel like we’re being told to do something like turn off a spigot, and it’s not that easy. And I said: Well, there are 3 cases in the world literature. But their question that was poignant is really what you started with, Ruth, which was: Is there enough information that says that the amount of drug that gets across to my baby is worth depriving my baby of the breast milk? And that’s something we still forget; so often it’s: Well, you have to take a drug, just stop breastfeeding. You have formula; no big deal. And progressively, more information is available to show that we might avoid an error of commission. We give a drug to a woman, maybe the baby has an allergic reaction (which I’ve never seen), or some odd event, but the error of omission -- not allowing the breastfeeding, particularly the health outcomes -- are I think criminal. But we don’t tend to think like that.

But related to that, I want to ask my pediatric colleagues, there’s a constant pressure to say: Okay, fine, what do I look for in the kid? And certainly growth across time is one issue. The reason that I started out with “let’s look and see what the baby does before you start the breastfeeding” was my own panic experience of the first woman I treated with nortriptyline who was breastfeeding her baby. She called me several days later and said the baby was really groggy. I asked her to bring the baby in. We got a serum; nothing in the serum level. The husband comes in and says: I’ve been telling you the baby’s been like that all along! So this idea of really getting a sense of what the baby’s like -- but babies change; they’re different day to day, week to week. So from a pediatric standpoint, if you’ve got a mom taking a drug, let’s say fluoxetine, in your practice, what would cue you to get a level, or that monitoring should include X? Because it’s something that the pediatricians ask a lot. And there’s the long-term weight gain, but what about more short-term? From your standpoint, what would warrant getting a level?

Dr. Bogen: Moms are the best observers of their babies; way better than the pediatrician. We see them for a snippet in time, so I rely mostly on history and what the mother tells me; if the child’s had a dramatic change in behavior; like sleeping more, irritable, crying and not relieved by holding and cuddling, change in muscle tone, things where the baby just didn’t seem the same as before. Gassiness is probably one I would try to avoid because that seems to be a very common complaint for babies. Is it related to the food the mom ate? Maybe. But I would look at more general neurologic function. Are they irritable? Are they fussy? Is there some sense that the child isn’t well? But that’s also mixed with the mom’s anxiety and anxiousness about her treatment, so you have to balance that. But again, they would be more general things than change in tone.




Slide 52. The other thing is a lot of women don’t realize you can do both: breastfeed and bottle feed. What I’ve seen for a lot of the women who have depression is that sleep is really important for them, and if they miss their sleep, it’s really hard for them to function. So sometimes, what I tell women is: Do you know that you can do both? You can breastfeed all day long, and you can go to bed at midnight and get up at 6:00 in the morning and have someone feed the baby at night. Would that make your life better? Would that make you want to continue to breastfeed? Give her permission to give that formula, and try to let her come up with a plan, for example, what is it about breastfeeding that’s so difficult? Is it the daytime feeds? Is it the nighttime feeds? If you can get 6 or 8 hours of continuous sleep, would that work for you?

So trying to have her problem solved around her issues and giving her permission to say: You know, if you’re going to give your baby a bottle of formula at night or even better, why don’t you take a breast pump, pump it before you go to bed, at 3:00 in the morning, your significant other can give it to the baby, if they have one. That’s part of the problem. If they don’t, what do you do for the mom who’s a single mom and doesn’t have that kind of support? But I tell her it’s not all or none; the more breast milk, the better. But there are other options that women have than just completely feeding at the breast. You can store milk; first thing in the morning, women can pump. Almost all women can pump out extra milk in the morning when they wake up, and they can save that for the night time feed the next night. So there are lots of options for them.




Slide 53. Dr. Wisner: One of the things that I often say is that the baby, especially the little babies, their main job is feeding. So one of the behavioral things I ask them to watch is the intensity of the suck during breastfeeding, and the length of time on the breast. If there are changes that are dramatic, is that reasonable? As opposed to being more irritable, which are much more judgmental.

Dr. Bogen: With time, babies should get more efficient and not less efficient as they breastfeed, as they age. But they also have growth spurts where they’re rapidly gaining, trying to get the mom’s milk supply to increase. So you have to ask: Is this a 1 or 2 day event, or has this been a week-long event where the baby’s just been at the breast constantly or rapidly increasing? If it’s 1-2 days and then it goes away, you can just say: Well, maybe that was a growth spurt. But if it’s persisting, the other question for me is then: Is it really a milk supply issue or is it a baby behavior? And so we do test weights in our office a lot to reassure moms that the babies are getting enough to eat. We weigh the baby a couple of times in the clothing they’re going to wear, and then have the mom nurse, and then see how the weight gain is when you repeat the weight. And that’s very reassuring for mothers who are worried. What I see most in my office for women with depression is that they have a lot of worry. They worry about their baby getting enough to eat. They worry about whether they are doing things right, and anything we can do to reassure them that it’s going well can help. But in terms of change in length, again, if it’s brief, I’m fine with it; if it’s longer, I think more about milk supply. Is the baby latched properly? Is there thyroid disease, or other things that can cause low milk supply in the mom? But I can’t say that I’ve ever really thought about the change in behavior related to the drug per se. I don’t know if other people have.

Dr. Lawrence: Except for being a little sleepy, and this one I mentioned earlier was a fluoxetine issue which we don’t normally recommend, but I guess it was the only drug the clinician could think of. And the baby, instead of feeding every 2-3 hours was eating only five times a day. Cause and effect was clear when they were able to maneuver the medication, and then the mother was settled in on her sertraline. The baby was fine, went back to feeding every 3 hours, was gaining weight and so forth. Usually it’s not that dramatic, but I think it does help to schedule the dosing. Most of the time, you’re using once a day and it’s about 2 hours post-dosing to peak plasma time. So just don’t feed in that 2-hour time and you can keep the levels lower and not measurable, as we saw in most of the studies.

I just want to mention that another part of the equation for some women seems to be -- and I’d be curious what my colleagues, especially pediatric colleagues observe about this as well -- the temperament of the infant, because some infants are very happy to flexibly go from breast to bottle and back again and don’t mind that, and others are very averse to change and will refuse a bottle or get very fussy just because you’re asking them to transition from one to the other. Some babies who might be abruptly weaned don’t really care a whole lot because they just want to eat, and they don’t really care how they get it, but other babies care deeply and have an intense interpersonal experience at the breast that doesn’t happen in quite the same way at the bottle. Mothers typically know this about their babies; doctors often don’t inquire, and a doctor might advise a person to abruptly wean because she’s about to start a medication, or just be cavalier about that, often failing to take into account the nature of the relationship or the nature of the baby’s temperament.




Slide 54. Hilda B. Templeton, MD: I’m Hilda Templeton. I’m a psychiatrist who was in private practice for 22 years dealing primarily with antepartum and postpartum issues, and I’m presently a medical director with Pfizer. I would like to ask you to comment about the increasing widespread use off-label of atypicals in the treatment of major depression. I am aware that pharmaceutical companies are presently doing studies looking at the atypicals in major depression, whether it be treatment-resistant or not.

Dr. Wisner: Well, it’s certainly happening, and I’ve seen some of the studies with atypicals used specifically for depression, and not only treatment-resistant, but non-treatment-resistant depression. For so much of the work I do with childbearing women, I’m usually the last to use a new drug or a different drug that’s used for a new indication because I want it to have a lot of experience in the general population of women and really get the bugs worked out before I introduce it into my childbearing group of women. So I certainly haven’t used it for either depression or treatment-resistant depression in childbearing women, and would be relatively reluctant to for straight depression.

Where we are getting some experience is in patients who have bipolar disorder who are being managed with atypicals as anti-manic agents, and also with women with chronic psychosis, like schizophrenia, who are being managed and who are doing well and they generally have very good reason to continue their atypical antipsychotic. So we are now beginning to collect data, and part of what Hilda didn’t say is, we have a study to look at the pharmacokinetics of ziprasidone during pregnancy; it’s an issue that the FDA is very anxious to get addressed. And if we’re going to use drugs in pregnancy, why don’t we have pharmacokinetic data on these agents? We kind of just wing it and use doses for nonpregnant patients. So it’s a very compelling issue to think about. How are we going to get the data to inform these decisions? And Laura probably uses more atypicals than I do.

Dr. Miller: Yes. Similarly to what you’re saying, for the same exact reasons, I don’t use them for unipolar depression, but do use them as alternatives for people that have bipolar disorder during pregnancy when the conventional mood stabilizing medications pose too many risks, or sometimes in cases of postpartum psychosis that are bipolar in nature where a mood stabilizing property and an antipsychotic property can be had with one medication instead of with two. So those are the kinds of indications that are beginning to be reasonable, particularly after the publication of the Motherisk study of the atypical antipsychotics during pregnancy, which was a prospective controlled study of a group of people contacting the Motherisk program in Canada or the Israeli Teratogen Information Service. It’s not a lot of data, but it’s a really good start.




Slide 55. Linda H. Chaudron, MD, MS: I have a comment and a question. I’m wondering, as we think about systems, I have run up against the scenario where you may choose sertraline as your first choice because we have the most data, or you feel the most comfortable with it in breastfeeding, and the patient is antidepressant-naïve, so you don’t have a history. The insurance company says: Sorry, not on your formulary. And you have no argument, really, I would say, unless other people can think of a way to do anything but give fluoxetine or citalopram. I’m just wondering what other people’s experiences have been, and is there any movement, or should we consider any movement around perinatal women to be addressing these issues at yet another level with our insurance companies?

Jeanne Watson-Driscoll, PhD, APRN, BC: In my own clinical practice, I’ve had episodes where the insurance company, through the pharmacy, has refused the medication, and I’ve been able to use a prior authorization request, giving documentation of the use of sertraline in breastfeeding and the data, if they were refusing to use that one, and I’ve gotten approval. I haven’t had any trouble.




Slide 56. Dr. Chaudron: My other comment is the issue of use of medication during pregnancy and then transitioning to breastfeeding. So many times you run into OB/GYNs feeling comfortable with fluoxetine, and pediatricians feeling comfortable with sertraline, and moms feeling caught between the differing opinions. And are we at a point (which I think we are), to be able to say there’s not really one that is better in either case, again, based on the person’s personal history? But I think that’s a critical issue because there isn’t a statement in any way, and I’ve had many moms who come to me and they say: I’m on this in pregnancy, but I want that safe breastfeeding drug. And which one was that? Well, my obstetrician told me you’ll tell me the safe drug. Well, there isn’t one! So I think that’s a critical question. I also would be interested in your comments on often moms will feel comfortable using a medication in pregnancy, and then not want to breastfeed, even though they’ve exposed their baby throughout pregnancy, and how people are addressing that to help moms make an informed choice.

Dr. Wisner: Well, I can take that second piece about moms who take a particular medication in pregnancy but choose not to breastfeed, which throws me in the same way because the amount of exposure across the placenta is dramatically more than what gets into the baby through breast milk. But when the situation has happened -- and it happens with more frequency than I wish -- what typically comes up in the discussion is something like: Well, I needed the medicine and I took it in pregnancy because I felt that was best for me and the baby for the baby to grow, and I didn’t have a choice about exposing the baby. With breastfeeding, I have a choice. In that whole risk/benefit piece are these attitudes and feelings and belief sets that some women have; there are other ways of thinking that they identify themselves as good moms. And so going back to the mother’s own valuation of that risk/benefit process is that I think it results in some of these decisions that to us don’t seem very scientifically based, but then again the whole process isn’t very scientifically based! I think that the comment that I made at the very beginning about what’s the best drug, it’s a drug that works for you really plays out here and that’s my primary approach. But again, in this risk/benefit decision-making, they read the Internet, and they talk to their pediatrician who says you’ve got to take sertraline, and they’re on fluoxetine in pregnancy because that’s what the OB wanted, and you present the information and despite my whatever-works-for-you stance, I do have a number of women who say: Well, you know, I’m going to taper off fluoxetine to avoid that neonatal syndrome, and then start back on some other drug postpartum because that’s the way I want to manage it. And I don’t think it’s ideal, and unless they’ve had experience with it, they’re risking taking a drug that doesn’t work. However, again, some women seem to make those choices and I think to some extent, we have fed into some of that with some of the earlier publications. And even in my own work, I wish I had made the statement that I now make in my papers, which is a drug that has known efficacy for that patient must be the primary consideration. I didn’t make that blatant a statement before in my career either and I think that was a mistake.




Slide 57. Seth Rubin, MD, MSCP: I think that also the provider/patient relationship -- if you have an established relationship with a patient, they’re more likely, not always -- but they’re more likely to really trust what you have to say and to follow the recommendations. If it’s a new patient that you haven’t treated before, that relationship hasn’t been established. I also think it’s surprising there haven’t been more pharmacokinetic studies of atypicals during pregnancy, because particularly with the effects on glucose metabolism in people in general, but particularly in pregnancy, that would be a huge issue; so I’m surprised that there hasn’t been. I’m wondering if any of you can make any comments about the use of mood stabilizers in breastfeeding. It was mentioned a couple of times, but not too much about specifics of the use of valproic acid or other types of medications.

Dr. Miller: In terms of mood stabilizers during breastfeeding, there are a few that concern me more than others. One of them is lithium in the sense that it does get into baby serums in appreciable levels, and the problem is not just so much the level in and of itself, but the ratio between what’s toxic and what’s therapeutic is relatively narrow. So that if a baby gets dehydrated, as babies are apt to do because they spit up or because they get a fever or because they have diarrhea or what have you, the ability to become toxic from what was not a toxic level is worse in the case of lithium than in some others. Not that it’s an absolute contraindication, but it’s a real cautionary note.

The other 2 that I have particular concern about with babies and breastfeeding are Lamictal^® (lamotrigine) and Trileptal^® (oxcarbazepine) because these are 2 that can in quite rare cases cause fatal rashes. Babies all get rashes; almost all the rashes that babies get are very benign, but at the beginning, it’s not so easy to tell whether a rash that has developed in a baby is a benign normal baby rash, or whether it could be the beginning of a very serious medication-induced rash. And just the anxiety level that mothers experience from wondering whether it might be a medication-induced rash is in and of itself problematic, along with the need to confer with pediatricians frequently. Again, I don’t think it’s an absolute contraindication, but I think it’s a cautionary note.

Depakote^® (valproic acid) is one that because it is a weak acid and breast milk is acidic, gets into breast milk less than many other medications do, so while there are quite a few cautions about its use during pregnancy, less so with its use during breastfeeding.

Dr. Wisner: Do you have the same worry about carbamazepine with the rash?

Dr. Miller: Yes. Carbamazepine is very comparable chemically to oxcarbazepine, but so far, to my knowledge, it has not been as much associated with rashes. But that could be accidental, because when something is that rare, it just takes a while to notice an association.

Dr. Wisner: What about atypicals?

Dr. Miller: With atypicals, as many have already pointed out, there are so few data so far in terms of breastfeeding, but the difference in general I think with breastfeeding and pregnancy is that the breastfeeding baby is not a black box. You can observe the baby and you can check a serum level. So with antidepressants, I don’t routinely check serum levels unless the baby’s looking like something has dramatically changed. With a medication that a woman really appears to need and that is very effective for her but is unstudied in breastfeeding babies, it remains an option to go ahead and breastfeed, to watch the baby, and to check a serum level on a more routine basis, because if the level is nondetectable and the baby appears to be thriving, even in the absence of more systematic data, some women will still choose to breastfeed. So it still remains an option.

Dr. Lawrence: When do you screen the baby? What age range do you screen the baby, get a blood level on the baby?

Dr. Miller: Usually just when the medication would have reached steady state in the mother. I would be more concerned about a younger baby (less than 2 weeks old), than with a baby who was 8 weeks old or older.




Slide 58. Irene Frederick, MD: I want to comment on Laura’s comment, which is a really good one, about the relationship between sexual abuse in an individual, and the whole breastfeeding thing, and how that relates specifically to depressive symptoms. We’ve had in the past 3 years about a half a dozen patients who during the pregnancy were very positive-feeling about breastfeeding, had counseling with our lactation person who’s also our perinatal social worker. Kathy McGrath and Penny Simpkin are probably two of the most significant doulas in the country, and together they have written a book about the impact of sexual abuse on the childbearing experience, and this is one of the things that they have actually identified and bring up in the book; this relationship between a very adverse physical reaction which gets translated into depressive symptoms most of the time when the mother actually puts the baby to the breast. And these have all been prima gravidas with no prior history of trying to breastfeed.

And when they’ve put the babies to the breast -- some of them it happens almost immediately; others it’s taken as long as a month for them to present to us with these symptoms of depression. And it’s only because Kathy is extremely astute at weeding out what’s really going on and has actually traced this back to being that the mother had this history of sexual abuse; it was somehow breast-centered, which it often is in children, especially young peripubertal girls who are starting to get breast development, and that is how they’re abused. In all of these situations, Kathy was able to walk them through options and about half of them chose to pump and give the baby the breast milk that way, and that was a very effective way of avoiding the whole issue of getting that baby to the breast; the baby still got the breast milk. And in all 3 of those cases, all the depressive symptoms went away. So this was not depression causing the problem; this was the problem causing depression. And the other 3 just opted, for various reasons, not even to pump. But that is something to always consider; that pumping and giving the baby the milk that way is still getting breast milk into the baby.




Slide 59. Cynthia Logsdon, DNS, ARNP: I just want to ask the panel what your experience has been with lactation consultants and La Leche League with providing accurate information to women being treated with antidepressants who choose to breastfeed.

Dr. Wisner: Well, our lactation consultant is Dr. Debra Bogen. Deb works with the women in our research project, and it’s been a real eye-opener for me to hear some of them interact with her, and the kinds of questions they ask and the kind of support that she provides. This has been a real eye-opener because if we’re trying to treat depression in this much more holistic way, some of the examples that Irene gave and Deb talks about: Let’s problem-solve, let’s do this, try this. This whole interactive piece that says I care about you as a woman, a mother, a person in the world, is really a fantastic thing, but we’re very lucky to have Deb.

Prior to Deb, my experience in Pittsburgh and Cleveland both has been fairly positive about lactation consultants and the La Leche League in general in that they were some of the early people who were even interested and even gave a darn about the research that I was doing and weren’t on the track of: Oh, my Lord, you’re going to stick a needle in a baby’s arm and draw blood! They were much more reasonable: Let’s look at the whole picture, let’s get the information. So I have seen them largely as allies and important folks to help get real information, scientific data out rather than lore. So I’ve had positive experiences.

Dr. Bogen: I’ve had experience with a lot of lactation consultants, not so much with La Leche League because I serve mostly an inner-city population, and La Leche League is wonderful in the outlying communities of Pittsburgh, but not so much in the city. The lactation consultants that I’ve worked with have all been very positive about treatment; they are just happy that the women are breastfeeding. The biggest problem for breastfeeding in general is that there is so much misinformation out there from all sources -- from doctors, from nurses, from the lay community. I spend half my time in Kathie’s office trying to figure out what women know and don’t know that’s accurate. They have so much misinformation; it’s unbelievable. And more than half of it comes from the medical community. I’ve had women stop breastfeeding because they were put on Synthroid^® (levothyroxine); because they were having an upper GI and needed to swallow some barium; because they thought that their medication was not compatible; because they smoke 5 cigarettes a day -- the list is extensive. And I think just educating people about the fact that you can breastfeed and take medications -- even Tylenol^® (acetaminophen), is important. I have women who will bear enormous amounts of pain and they won’t take acetaminophen because they’re breastfeeding. The misinformation is enormous, so again, I spend half my time when I do a lactation consult, trying to undo misinformation that people have received from various sources; so it’s just sort of data gathering: What have you heard, and where have you heard that, and do you believe that? What do you think? It’s amazing. But the lactation consultants in general have been fabulous in supporting women to breastfeed across all medications, really trying to figure out a way, like Dr. Lawrence said, of giving the medication in a way that’s as safe as possible.

Dr. Lawrence: Well, just on a final note, all lactation consultants are not equal. You want a certified lactation consultant who is licensed to practice something, whether it’s nursing or dietetics.