Title:

Taking Antidepressants While Breastfeeding: Duration, Risks, and Long-term Effects
Purpose: The purpose of this activity is to educate healthcare providers on how to assess, screen, diagnose, treat, and refer patients with postpartum depression.
Target Audience: This activity is intended for healthcare providers (pediatricians, obstetrics-gynecology, psychiatry, nursing, social workers) who provide care to patients of childbearing age and/or pregnant patients.
Presenter: Ruth A. Lawrence, MD, FAAP, FACCT, FABM
Panel: Debra Bogen, MD, FAAP; Laura Miller, MD; Katherine L. Wisner, MD, MS
Reviewer(s): Caroline Hewitt, RNC, MSN, WHNP, ANP; Cheryl Smith, MD; Melanie Steilen, BSN, RN, ACRN
Description: Dr. Lawrence discusses issues regarding pharmacologic treatments for postpartum depression. She specifically addresses taking medications while breastfeeding, and provides data on breast milk and blood serum concentrations of drugs currently being used to treat postpartum depression.
Credits: 1 CME credit(s)
Learning Objectives: Upon completion of this activity, participants should be able to:
1. Discuss the merits of breastfeeding for depressed and nondepressed women.
2. Evaluate various antidepressant options, potential side effects, and implications for use while lactating.
3. Use a model of risk-benefit decision making for antidepressant use during lactation.
4. Cite the evidence base to address concerns regarding short- and long-term development of infants exposed to antidepressants through breastfeeding.
5. Identify drugs of choice for breastfeeding as defined by nonquantifiable breastfed infant serum levels, and the number and types of reported adverse events in infants.
Accreditation(s):
CME: This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through Cicatelli Associates Incorporated (CAI). CAI is accredited by the ACCME to provide continuing medical education for physicians and takes responsibility for the content, quality and scientific integrity of this activity.

CAI designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Nursing Contact Hours: CAI is an approved provider of continuing nursing education by the New York State Nurses Association Council on Continuing Education, which is accredited as an approver of continuing education in nursing by the American Nurses Credential Commission on Accreditation. It has been assigned code: 653NHU-PRV-04-152 -- 1.5 Nursing Contact Hours will be awarded.

If you wish to receive CME non-physician credit, please complete the Physician Program. If you wish to receive Nursing Contact Hours, please complete the Nurse Program.
Disclosure(s): The "Faculty Disclosure Policy" of the ACCME requires that faculty participating in a CME activity disclose to the audience any relationship with a pharmaceutical or equipment company which might pose a potential, apparent, or real conflict of interest in regard to their contribution to the activity, and any discussions of unlabeled or investigational use of any commercial product or device not yet approved in the United States.

Ruth A. Lawrence, MD, FAAP, FAACT, FABM has no relationships to disclose. Debra L. Bogen, MD has no relationships to disclose. Laura Miller, MD has no relationships to disclose. Katherine L. Wisner, MD, MS is on the speaker?s bureaus of Pfizer and Glaxo Smith Kline.

There are no commercial supporters of this activity.
 
Release Date: November 1, 2006; Valid for credit through October 31, 2008

Copyright 2006 Cicatelli Associates Inc. Provider Number: 0007155

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Follow these steps to earn CME/CE credit:
  1. Read the target audience, learning objectives, and author disclosures
  2. Study the educational content online or printed out.
  3. Online, choose the best answer to each test question. To receive a certificate, you must receive a passing score of 80% or higher. In addition, you must complete the activity evaluation to provide feedback for future programming.
You may view or print the certificate upon completion of the activity evaluation. You may print the certificate but you cannot alter it. Credits will be tallied and archived with your profile for 6 years. At any point within this time period you can print out the tally as well as the certificates. The credit that you receive is based on your user profile.
   
NASW Credit
(Social Workers):
This program was approved by the National Association of Social Workers (provider #886471152) for 1 contact hour.




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.

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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 itís 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 itís brain growth or general growth or protection or whatever it is, weíve 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 doesnít contain any cholesterol. Taurine is an amino acid specific to human milk, and of course DHA (docosahexaenoic acid); youíve 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, itís 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 Crohnís 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 itís another one of the great reasons to consider providing human milk for the infant.




Slide 8. We know that when thereís 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: Itís 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 donít 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, Iím going to give you a terrible drug, so stop breastfeeding today -- thatíll precipitate a psychiatric crisis. So itís not recommended.




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




Slide 14. Itís the risk/benefit ratio. Weíve 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 isnít 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; itís very different than just considering the drug for the mother. Can the infant absorb the drug? If this is a medication thatís poorly absorbed in the gut or poorly absorbed with food, the baby isnít 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 somebodyís 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 weíre talking about ambulatory women who are taking their medications by mouth, but sometimes theyíre given intravenously or intramuscularly, and now that the transdermal delivery system has become very common, Iím sure many of the medications you use will soon be available as a patch. What youíre 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 itíll 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 weíre not going to be clearing most of these medications, but we will be assuming a steady state. And when youíve 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, letís 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 hasnít much left in the plasma, hasnít 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 donít 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; thatís 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 donít 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 itís 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 wonít reach the milk?




Slide 19. Pharmacologists like to look at drugs in a scheme like this, so I thought Iíd 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 itís 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 youíre 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 donít use them very much anymore, but I keep this slide because itís such a good demonstration of the fact that hereís a whole family of medications that youíd 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 thereís just as much in the milk as there is in the plasma. Well, if you can take your choice, youíre 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 weíll 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, itís going to be absorbed with food, and then itís 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 itís long-acting for 12 hours for an adult, itís 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 isnít 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 youíre trying to reach a steady state for postpartum depression, it isnít 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 infantís serum, and there were no adverse effects; this is actually one of the drugs of choice for treating postpartum depression, and itís usually the one our lactation study center drug center would suggest.




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




Slide 30. Most of the time we donít 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 babyís growth curve just went down. And he said: Do you think thereís any correlation? We discussed it for a few minutes and recommended that he change the motherís 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 donít 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 donít think we can say absolutely that thereís 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 youíll notice on this graph that the left-hand figure is what happened to the mothersí 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 itís 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, itís certainly a possibility. And then thereís 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 (contíd)




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 theyíve studied that use of the drug. Nowhere in the PDR does it say itís appropriate to use a medication during lactation, because they havenít studied it, and they are not going to study it because theyíre not going to invest money -- theyíd just as soon lose that market as spend money to explore it. And if they donít explore it, they canít say anything about it.




Slide 41. So the PDR has never said a drug was good in lactation and itís almost true for pregnancy, although theyíve done some studies and met the requirements. So the fact that the PDR doesnít 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 donít say anything they canít 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 donít 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. Johnís wort vs amitriptyline, and for mild depression, apparently the clinical impact was very effective with St. Johnís 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. Johnís wort you want. This is a problem; that many mothers think if you can buy it across the counter, itís okay; and probably the biggest problem is that they need to have an appropriate diagnosis. Iíve 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, itís 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 youíve written so much on this subject, maybe youíd like to comment.




Slide 47. Katherine L. Wisner, MD, MS: Well, I actually have a somewhat different first response when Iím asked the question: What is the best drug for a depressed woman to take for postpartum depression if sheís breastfeeding? And my usual response is: The antidepressant that works for her. One of the major issues is you donít want to pick a theoretical ďbest drugĒ 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 thatís such a negative choice for breastfeeding that you should use another drug over it. Letís say fluoxetine -- which is in theory the least desirable drug to use for breastfeeding as Dr. Lawrence points out because itís got a long half-life, and itís 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 sheís 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 ďno.Ē So if thereís a drug that works, I use that. If thereís no treatment history, thereís 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 womanís 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 youíre saying; if I switch to a different drug, thereís a risk that I might not respond. But, you know, that stuff I heard scares me, so Iím 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 theyíre reasonable to do so. In a greater context, I think weíre incredibly lucky to have the amount of data about antidepressants for use in breastfeeding that we do. Itís 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 weíre actually rather lucky in this arena.

Debra Bogen, MD, FAAP: Iím going to approach this from a pediatricianís point of view because thatís what I am, so itís 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 canít 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 theyíre missing out on a wonderful opportunity. So I try to encourage women to get treatment. Thatís 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 donít want to take drugs a lot of the time. Itís a real barrier for them. They just feel like they want to keep it pure; they avoided medications during pregnancy, and theyíre 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 theyíre not getting better, encourage them to take a medication; that itís perfectly safe. And I think thatís one thing I can tell women is based on the literature, based on my experience, itís perfectly safe for them to take antidepressant medications during pregnancy. I donít prescribe them myself. I donít think thatís 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 babyís 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 thatís 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 Iím going to take out of my life. Among that subset, itís 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 thatís 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 babyís baseline, then one can get a serum level. If the level is nondetectable, as it frequently is, itís going to key people in to look for other causes of that whatever-it-is symptom, and not automatically assume that itís the medication and that the breastfeeding has to abruptly stop.

A third issue I want to underscore is youíre talking about the limitations of looking to the PDR as a source of information about medications during pregnancy and breastfeeding, but then again, if weíre going to point out the limitations, we need an alternative place to look, and one product that weíve 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 thatís 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 wouldnít, 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 itís before they start, then I would really wonder if itís because they anticipate that the woman might need a medication, and theyíre 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 Ruthís 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 canít take an antidepressant and breastfeed. And we feel like weíre being told to do something like turn off a spigot, and itís 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 thatís something we still forget; so often itís: 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 Iíve 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 donít tend to think like that.

But related to that, I want to ask my pediatric colleagues, thereís 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 ďletís look and see what the baby does before you start the breastfeedingĒ 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: Iíve been telling you the babyís been like that all along! So this idea of really getting a sense of what the babyís like -- but babies change; theyíre different day to day, week to week. So from a pediatric standpoint, if youíve got a mom taking a drug, letís say fluoxetine, in your practice, what would cue you to get a level, or that monitoring should include X? Because itís something that the pediatricians ask a lot. And thereís 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 childís 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 didnít 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 isnít well? But thatís also mixed with the momís 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 donít realize you can do both: breastfeed and bottle feed. What Iíve seen for a lot of the women who have depression is that sleep is really important for them, and if they miss their sleep, itís 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 thatís 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 youíre going to give your baby a bottle of formula at night or even better, why donít 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. Thatís part of the problem. If they donít, what do you do for the mom whoís a single mom and doesnít have that kind of support? But I tell her itís 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 theyíre rapidly gaining, trying to get the momís 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 babyís just been at the breast constantly or rapidly increasing? If itís 1-2 days and then it goes away, you can just say: Well, maybe that was a growth spurt. But if itís 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 theyíre going to wear, and then have the mom nurse, and then see how the weight gain is when you repeat the weight. And thatís 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 itís going well can help. But in terms of change in length, again, if itís brief, Iím fine with it; if itís 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 canít say that Iíve ever really thought about the change in behavior related to the drug per se. I donít 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 donít 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 itís not that dramatic, but I think it does help to schedule the dosing. Most of the time, youíre using once a day and itís about 2 hours post-dosing to peak plasma time. So just donít 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 Iíd 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 donít mind that, and others are very averse to change and will refuse a bottle or get very fussy just because youíre asking them to transition from one to the other. Some babies who might be abruptly weaned donít really care a whole lot because they just want to eat, and they donít really care how they get it, but other babies care deeply and have an intense interpersonal experience at the breast that doesnít happen in quite the same way at the bottle. Mothers typically know this about their babies; doctors often donít inquire, and a doctor might advise a person to abruptly wean because sheís 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 babyís temperament.




Slide 54. Hilda B. Templeton, MD: Iím Hilda Templeton. Iím a psychiatrist who was in private practice for 22 years dealing primarily with antepartum and postpartum issues, and Iím 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, itís certainly happening, and Iíve 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, Iím usually the last to use a new drug or a different drug thatís 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 havenít 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 didnít say is, we have a study to look at the pharmacokinetics of ziprasidone during pregnancy; itís an issue that the FDA is very anxious to get addressed. And if weíre going to use drugs in pregnancy, why donít we have pharmacokinetic data on these agents? We kind of just wing it and use doses for nonpregnant patients. So itís 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 youíre saying, for the same exact reasons, I donít 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. Itís not a lot of data, but itís a really good start.




Slide 55. Linda H. Chaudron, MD, MS: I have a comment and a question. Iím 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-naÔve, so you donít 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. Iím just wondering what other peopleís 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, Iíve had episodes where the insurance company, through the pharmacy, has refused the medication, and Iíve 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 Iíve gotten approval. I havenít 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 thereís not really one that is better in either case, again, based on the personís personal history? But I think thatís a critical issue because there isnít a statement in any way, and Iíve had many moms who come to me and they say: Iím on this in pregnancy, but I want that safe breastfeeding drug. And which one was that? Well, my obstetrician told me youíll tell me the safe drug. Well, there isnít one! So I think thatís 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 theyíve 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 didnít 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 motherís own valuation of that risk/benefit process is that I think it results in some of these decisions that to us donít seem very scientifically based, but then again the whole process isnít very scientifically based! I think that the comment that I made at the very beginning about whatís the best drug, itís a drug that works for you really plays out here and thatís my primary approach. But again, in this risk/benefit decision-making, they read the Internet, and they talk to their pediatrician who says youíve got to take sertraline, and theyíre on fluoxetine in pregnancy because thatís 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, Iím going to taper off fluoxetine to avoid that neonatal syndrome, and then start back on some other drug postpartum because thatís the way I want to manage it. And I donít think itís ideal, and unless theyíve had experience with it, theyíre risking taking a drug that doesnít 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 didnít 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, theyíre more likely, not always -- but theyíre more likely to really trust what you have to say and to follow the recommendations. If itís a new patient that you havenít treated before, that relationship hasnít been established. I also think itís surprising there havenít 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 Iím surprised that there hasnít been. Iím 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 whatís toxic and whatís 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 itís an absolute contraindication, but itís 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, itís 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 donít think itís an absolute contraindication, but I think itís 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 donít routinely check serum levels unless the babyís 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 Lauraís 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. Weíve 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 whoís 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 theyíve put the babies to the breast -- some of them it happens almost immediately; others itís taken as long as a month for them to present to us with these symptoms of depression. And itís only because Kathy is extremely astute at weeding out whatís 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 theyíre 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 itís 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 weíre trying to treat depression in this much more holistic way, some of the examples that Irene gave and Deb talks about: Letís problem-solve, letís 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 weíre 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 werenít on the track of: Oh, my Lord, youíre going to stick a needle in a babyís arm and draw blood! They were much more reasonable: Letís look at the whole picture, letís 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 Iíve had positive experiences.

Dr. Bogen: Iíve 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 Iíve 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 Kathieís office trying to figure out what women know and donít know thatís accurate. They have so much misinformation; itís unbelievable. And more than half of it comes from the medical community. Iíve 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 wonít take acetaminophen because theyíre 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 itís just sort of data gathering: What have you heard, and where have you heard that, and do you believe that? What do you think? Itís 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 thatís 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 itís nursing or dietetics.



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