BREASTFEEDING MEDICINEVolume 3, Number 1, 2008© Mary Ann Liebert, Inc.DOI: 10.1089/bfm.2007.9978 ABM Clinical Protocol #18: Use of Antidepressants in Nursing Mothers THE ACADEMY OF BREASTFEEDING MEDICINE PROTOCOL COMMITTEE A central goal of The Academy of Breastfeeding Medicine is the development of clinical proto-cols for managing common medical problems that may impact breastfeeding success. These pro-tocols serve only as guidelines for the care of breastfeeding mothers and infants and do not de-lineate an exclusive course of treatment or serve as standards of medical care. Variations intreatment may be appropriate according to the needs of an individual patient.
Volume 3, Number 1, 2008
Mary Ann Liebert, Inc.
ABM Clinical Protocol #18: Use of Antidepressants in Nursing Mothers THE ACADEMY OF BREASTFEEDING MEDICINE PROTOCOL COMMITTEE A central goal of The Academy of Breastfeeding Medicine is the development of clinical proto-cols for managing common medical problems that may impact breastfeeding success. These pro-tocols serve only as guidelines for the care of breastfeeding mothers and infants and do not de-lineate an exclusive course of treatment or serve as standards of medical care. Variations intreatment may be appropriate according to the needs of an individual patient. medication to the infant and mother, and thebenefits of treatment. This Protocol discusses With estimates of between 5% and 25% of the importance of actively screening for and, women experiencing depression in the post- when present, making the diagnosis of post- partum year,1–3 it is critical that healthcare partum depression, how treatment can be de- providers consider all treatment options, in- termined, and specifically addresses the med- cluding the risks and benefits for nursing moth- ications for which there is sufficient evidence ers. Many healthcare providers recognize the to make recommendations and provide data short- and long-term negative effects that post- (selective serotonin reuptake inhibitors [SSRIs] partum depression can have on mothers and and tricyclic antidepressants [TCAs]/hetero- infants.4–6 Despite this, postpartum depression cyclics). We recognize that this is a complex is- often goes undetected and untreated.2 Post- sue, and that there are many other factors that partum depression is a treatable illness. Treat- impact the care of women with postpartum de- ment options include psychotherapy (cognitive- pression, but which are beyond the scope of behavioral, interpersonal psychotherapy),7–9 this protocol to discuss.
antidepressants,8,10,11 or a combination of med-ication and therapy.8 The choice and approachto treatment can be influenced by many factors, CLINICAL APPROACH TO IDENTIFYING
including the mother's wish to breastfeed.
Women may not receive medication, or receiveinadequate doses, because they are breastfeed- Postpartum depression is often missed by ing, or may decide not to breastfeed because providers and mothers.2,12–14 The symptoms they are concerned about medication use dur- of depression—depressed mood, sleep disrup- ing lactation. Full consideration must be given tion, weight loss, fatigue, difficulty concentrat- to the risks of untreated depression, risks of the ing, anxiety, loss of interest in usual activities— can be difficult for mothers and providers to benefit of providing lasting changes in coping distinguish from the normal experiences of skills and adaptation to the new role of moth- new mothers. It is also important to differenti- ate mothers suffering from postpartum de- If psychotherapy is unavailable or unaccept- pression from those with postpartum blues as able to the mother, or the symptoms are severe, misdiagnosis of such mothers can lead to un- antidepressants are an effective option. The ap- necessary treatment. To distinguish symptoms proach to choosing an antidepressant is based of depression from the "baby blues," the tim- on a variety of factors. No antidepressant is ing (2 weeks in duration, all day nearly everyday) and the severity (functional impairment) TABLE 1. RECOMMENDATIONS FOR IDENTIFYING WOMEN must be evaluated.15 WITH POSTPARTUM DEPRESSION For many women, acknowledgement of feelings other than happiness following the • The preferred method for identifying women with postpartum depression is the systematic use of a birth of their infant can be devastating and validated screening tool such as the Edinburgh embarrassing. If mothers have thoughts of Postnatal Depression Scale16 or the Postpartum harming themselves or their infant, they are Depression Screening Scale17–19 at the obstetrical often afraid to bring these issues to their ob- postpartum visit and at well childcare visits in thepostpartum year.
stetrician, family physician, pediatrician, mid- • Ask mothers if they feel down or anxious. Many wife, child health nurse, or other healthcare women with postpartum depression report anxiety professional for fear that they will be labeled as a primary symptom rather than depressed moodor anhedonia. Excessive worrying about the baby's "crazy" or that their children will be taken or mother's health should be explored.
away. Therefore, many women will not bring • Ask mothers if they are having trouble sleeping even up their concerns or even identify them as a when they are exhausted and their child issleeping20 or if they are sleeping all the time and are problem unless providers ask specific ques- unable to get out of bed.
tions or use a screening tool (see Table 1). De- • Ask mothers if they are losing or gaining weight.
pending upon the setting or the country, it is Many women with postpartum depression report a common for women to receive their peripar- poor appetite, but they eat because they need tokeep their strength up or for nursing. Some mothers tum and postpartum care from healthcare will gain weight.
providers other than physicians. In these cir- • Ask mothers directly but in an open, non- cumstances, communication between physi- threatening manner about thoughts or fears ofharming their children. For example, "Many new cians and these other healthcare providers mothers experience anxiety about their new infants.
may be crucial to making an accurate diagno- They may have thoughts that are unusual or frighten sis and initiating timely treatment.
them such as fears that they may harm their baby.
Does this ever happen to you?"21 Mothers whoexperience intrusive thoughts do not wish to harmtheir children and avoid the topics of their fears (i.e., CLINICAL APPROACH TO TREATING
a mother is afraid her baby will drown therefore will not bathe the baby and has her partner bathe theinfant). It is important to distinguish the womanwith postpartum depression whose intrusive Once a woman is identified as suffering from thoughts or fears of harming the infant are postpartum depression, the choice of treatment incongruent with the mother's wish to keep herinfant safe from the woman with postpartum must be considered. While no treatment is an psychosis who is delusional and who may have option, it is not the preferred approach. Post- thoughts of harming her infant to "save the infant partum depression may last for months to from the devil or a life of torment." Delusional years and can have long-term effects for the mothers are at great risk of harming their infants orthemselves and must be immediately evaluated by a health and well-being of mothers and in- fants.4,5,9,23 In breastfeeding women with mild • Ask mothers if they have concerns or questions to moderate depression, the first-line treatment, about adapting to a new baby.
• Consider the mother's interactions with the infant, if available, is psychotherapy. Psychotherapy including the responsiveness of mom and baby.
can be an effective treatment for women with • Difficulty in breastfeeding, or not enjoying postpartum depression and carries no risks for breastfeeding, may be a warning sign that should befurther evaluated.
the infants. Psychotherapy may also have the proven safer or more effective than another in CLINICAL FACTORS AFFECTING
the postpartum period or during lactation. The majority of drugs including all antidepressantsare excreted in breastmilk. Data to inform clin- • There is no algorithm for antidepressant ical decisions are derived primarily from case treatment choices in postpartum or lactating reports or case series. Therefore, the initial women; however, articles by experts in the treatment choice should be based on an in- field provide clinical guidance.28,29 formed clinical approach that takes into account • Obtain a history of previous antidepressant the patient's previous treatments for depression, treatment. In general, if a treatment was ef- the targeted symptoms, family history of de- fective in the past and was tolerated, and pression and their experiences with antide- there are no current contraindications, it is pressants, current and past medical disorders, the likely first choice of treatment.
current medications, allergies, side effects of • Obtain a family history of treatment of de- the medications, and maternal wishes. An in- pression. An immediate family member's dividualized risk-benefit analysis of the treat- history may be indicative of the mother's ments must be conducted (see Table 2).28 treatment response.
• Consider the primary symptoms that the medication will be targeting and the poten-tial side effect profile of the antidepressant.
TABLE 2. RISKS AND BENEFITS OF ANTIDEPRESSANT For example, if the mother is particularly TREATMENT IN LACTATING WOMEN anxious, a medication that might heighten • The risks of untreated postpartum depression anxiety would not be the first choice. If the mother is experiencing hypersomnia, a med- ° persistence of symptoms ication with sedation as a side effect would ° possible increase in severity of symptoms, including deterioration in functioning, and not be the first choice. If a mother has so- thoughts (or even actions) of self-harm or harm to matic complaints such as nausea or diarrhea, a medication that may induce diarrhea ° relationship discord would not be the first-line treatment.
° impaired parenting ° effects on the child's development (including behavior, social, and cognitive).
• The risks of treatment with antidepressants include: CHOOSING AN ANTIDEPRESSANT
° Maternal: side effects of the medication, potential drug interactions ° Infant: exposure through breastmilk transmission; limited data on the long-term effects on child When considering the use of any medication in a lactating woman, providers must consider • The benefits of treatment include the resolution of the factors that influence infant serum levels, depressive symptoms that, in turn, will potentially the most accurate measure of infant exposure.
improve maternal self-esteem, parenting, maternal-infant interaction, and child outcomes.24 Factors affecting the passage of medication into • The medical and psychological benefits of breastmilk must be considered (route of ad- breastfeeding to infants and mothers are well ministration, absorption rate, half-life and peak established.25–27 Depressed mothers may benefitadditionally from breastfeeding because of the sense serum time, dissociation constant, volume of of accomplishment and active, positive participation distribution, molecular size, degree of ioniza- in their infant's care and development.
tion, pH of plasma [7.4] and milk [6.8], solu- • The risks of breastfeeding for depressed mothers should be considered and may include: bility of the drug in water and in lipids, greater ° Sleep deprivation due to total dependence on the binding to plasma protein than to milk pro- mother may exacerbate or precipitate depressive tein), factors affecting the amount of drug re- ceived by the infant (milk yield, colostrum vs.
° If mothers are nursing and taking medications, the feelings of guilt and anxiety associated with mature milk, concentration of the drug in the exposing their infant to medication may exacerbate milk, how well the breast was emptied during their depressive symptoms.
the previous feeding), and an infant's ability to absorb, detoxify, and excrete the drug. Up-to- testinal distress, headaches, sexual dysfunc- date information about medication use during tion, nervousness, or sedation. Except for flu- lactation is available on TOXNET lactmed at oxetine, which has a half-life of 4–6 days, most SSRIs have a half-life of 24–48 hours. A newer, Most antidepressant studies provide milk related class of antidepressants, selective sero- levels, or milk to mother's plasma ratio, that tonin and norepinepherine reuptake inhibitors are not constant and depend on factors such as (SSNRIs or SNRIs), are becoming more widely dose, frequency, duration of dosing, maternal used because of what appears to be better effi- variation in drug disposition, drug interac- cacy with fewer side effects, especially for neu- tions, and genetic background. Few studies ropathic pain. Since the SSRIs have been in use provide infant serum levels, although they are longer and there are more data concerning lac- the best measure of infant exposure. Most stud- tation, this discussion will focus on the SSRIs.
ies suggest that infant daily dosages (calculated All SSRIs have been detected in breastmilk, based on maternal dose and milk levels) are although paroxetine31–33 and sertraline33–38 safest if the level is 10% or less of the "thera- usually produced undetectable infant serum peutic dose for infants (or the adult dose stan- levels.30 Neither of these medications has been dardized by weight)." found to exceed the recommended 10% mater-nal level. In contrast, fluoxetine,39–44 in 22% ofcases, and citalopram,33,45,46 in 17% of cases, have exceeded the 10% maternal level.30 Thereare virtually no case reports of escitalopram Data from a recent meta-analysis indicated and few case reports of fluvoxamine47–52 in that all antidepressants were detected in breast- nursing mothers, most likely because escitalo- milk but not all were found in infant serum.30 pram is only recently available and fluvoxam- Infant serum levels of nortriptyline, paroxetine, ine was indicated for obsessive compulsive dis- and sertraline were undetectable in most cases.
order, not depression, and therefore is not used Infant serum levels of citalopram and fluoxe- as frequently. In most studies, no infant ad- tine exceeded the recommended 10% maternal verse events are reported for any of these level in 17% and 22% of cases, respectively. Few medications. The few infant adverse events adverse outcomes are reported for any of the reported include uneasy sleep, colic, irritabil- antidepressants. There were an insufficient ity, poor feeding, and drowsiness.53–55 In one number of cases for all other antidepressants to case, an infant seizure was reported during the make conclusions.
time that the mother was taking fluoxetine.56However, the relationship of fluoxetine to thereported seizure was confounded by other medication exposures, and infant serum con-centration was not obtained.
The SSRIs are the most widely prescribed Although the association between fluoxetine antidepressant class and include citalopram and observed effects is uncertain, the long-term (20–60 mg), escitalopram (10–20 mg), fluoxe- effects on neurobehavior and development tine (20–80 mg), fluvoxamine (50–300 mg), from exposure to this potent serotonin reup- paroxetine (20–60 mg), and sertraline (50–200 take blocker, or any of the SSRIs, during a pe- mg). SSRIs improve depression and anxiety by riod of rapid central nervous system develop- blocking the serotonin transporter and thereby ment have not been adequately studied.57 In increasing serotonin availability in the synapse.
addition, the reduced weight gain identified in The medications are usually prescribed for de- one study may have clinical significance in pressive or anxiety disorders but may be pre- some situations, and should be monitored care- scribed for fibromyalgia, neuropathic pain, and fully in any breastfeeding baby whose mother premenstrual symptoms and disorders. Com- is on fluoxetine.58 The U.S. Food and Drug Ad- mon maternal side effects include gastroin- ministration specifically advised the manufac- turer to revise the labeling of fluoxetine to con- tain a recommendation against its use by nurs- Other common antidepressants include mir- ing mothers.59 The current labeling contains tazapine, an antidepressant that works by block- this revision.
ing the presynaptic noradrenergic receptors that Bearing all this information in mind, sertra- control norepinephrine and serotonin release, line and paroxetine are often the most likely to venlafaxine33,64 and duloxetine, which are be prescribed, because of their low to zero con- SNRIs, and bupropion, which is a norepineph- centrations in breastmilk. This is based on a rine and dopamine reuptake inhibitor. Sporadic presumption that there will be lower central case reports were found for these medica- nervous system effects compared to some of tions,65,66 and there are an insufficient number to the other SSRIs with higher breastmilk con- report significant outcomes for nursing infants.
One case report of a seizure in an infant exposedto bupropion through breastmilk is published, but attributing causation is cautioned.67 The TCAs (amitriptyline, amoxapine, clomipramine, desipramine, doxepin, mapro-tiline, nortriptyline, protriptyline, and trim- St. John's Wort, an herbal medication, has ipramine) are one of the older classes of anti- been used for the treatment of mild to moder- depressants. They are effective for the treatment ate depression for many years, especially in Eu- of depressive and anxiety disorders and are of- rope. Its use as a treatment for depression is ten used in low doses for sleep and chronic pain.
controversial in the United States. Only one The therapeutic mechanisms are most likely re- study of sufficient numbers was available for lated to the blockade of the norepinephrine review.68 In this study there were increased transporter, which thereby increases norepi- rates of colic, drowsiness, and lethargy in the nephrine availability in the synapses. These St. John's Wort group compared to controls, medications also block the dopamine and sero- but this was confounded by concomitant anti- tonin pumps, which may contribute to their depressant treatment in the study group. No therapeutic mechanisms. Unfortunately, they long-term effects were noted, and no effect on also block muscarinic cholinergic receptors, H1 milk production.
histamine receptors, and alpha-1-adrenergic re- Omega-3 fatty acids are currently being stud- ceptors, which most likely account for their ied as a treatment for depression during preg- wide array of unpleasant side effects. Despite nancy and the postpartum period.69 Omega-3 being effective and inexpensive they are not fatty acids appear to be of little risk to mothers used as frequently as SSRIs because of their side and infants as they are natural essential ele- effects, which can include hypotension, seda- ments of one's diet and are often depleted dur- tion, dry mouth, urinary retention, weight gain, ing pregnancy and breastfeeding. The primary sexual dysfunction, and constipation. In addi- negative side effect is the "fishy smell" and the tion, in an overdose, these medications can lack of sufficient evidence at this time to con- cause cardiac arrhythmias and death. Among sider it a treatment for depression.
this class of medications, only nortriptyline has There is little or no evidence that ethnic or a sufficient number of reported cases to com- regional "medicines" are safe or effective; thus ment on its use during lactation. In most cases, their use by healthcare providers is strongly nortriptyline is undetectable in infant serum. Its metabolite has been detected, but no adverseevents have been reported.60–62 Insufficientnumbers of cases have been reported on the other medications; however, use of doxepin is ANTIDEPRESSANT TREATMENT
often cautioned because of a case report of hy- IN LACTATING WOMEN
potonia, poor feeding, emesis, and sedation ina breastfeeding infant that resolved after dis- • Current evidence suggests that the risks of continuation of nursing.63 untreated maternal depression can have se- rious and long-term effects on mothers and and benefits of the treatment to make an in- infants and that treatment may improve out- formed decision.
comes for mothers and infants. Therefore • Mothers should be monitored carefully in treatment is strongly preferred.
the initial stages of treatment for changes in • However, it is important not to label moth- symptoms, including worsening of symp- ers who are only suffering from mild cases toms. Specifically, women with histories of of "baby blues" as "depressed." We must bipolar disorder, which may be undiag- make a distinction. If symptoms are mild, nosed, are at increased risk of developing a there is no reason to initiate antidepressant mood episode of depression, mania, or psy- medication treatment in the first 2 weeks chosis in the postpartum period. While this is rare, mothers and partners should be • When available and when symptoms are in made aware of the symptoms to watch for the mild–moderate range, psychotherapy is such as increased insomnia, delusions, hal- the first line of treatment for lactating lucinations, racing thoughts, and talking/ women as it carries no known risk for the in- moving fast and contact their mental health fant. Mothers must be monitored and re- evaluated. If they are not improving or their • Infants should be evaluated prior to the ini- symptoms are worsening, antidepressant tiation of a new medication during breast- drug treatment must be considered.
feeding and monitored carefully by the pe- • Psychotherapy in addition to antidepressant diatrician, including carefully following medication is recommended for women with growth. Serum levels are not indicated on a severe symptoms.
regular basis without a clinical indication or • Women with moderate to severe symptoms may request only antidepressant drug treat- • Strategies that may be used to decrease in- ment, and this must be considered as the fant exposure, but for which there is little ev- benefits of treatment likely outweigh the idence, include medication administration risks of the medication to the mother or in- immediately after feedings and pumping and discarding the breastmilk obtained dur- • There is no widely accepted algorithm for ing the peak serum levels.
antidepressant medication treatment of de-pression in lactating women. An individual-ized risk-benefit analysis must be conducted CONCLUSIONS AND SUGGESTIONS
in each situation and take into account the FOR FUTURE RESEARCH
mother's clinical history and response totreatment, the risks of untreated depression, Despite many publications of antidepres- the risks and benefits of breastfeeding, the sants and breastfeeding, the scientific literature benefits of treatment, the known and un- lacks both the breadth and depth for clinicians known risks of the medication to the infant, and mothers to make confident decisions about and the mother's wishes.
individual medications. Multiple reviews of • If a mother has no history of antidepressant the literature broadly suggest TCAs and sero- treatments, an antidepressant, such as parox- tonin reuptake inhibitors are relatively safe, etine or sertraline, that has evidence of lower and all recommend individual risk-benefit as- levels in breastmilk and infant serum and few side effects is an appropriate first choice.
The literature suffers from a lack of any ran- • If mothers have been successfully treated domized clinical trials in lactating women for with a particular SSRI, TCA, or SNRI in the any class of antidepressant. The majority of past, the data regarding this particular anti- studies are case reports or case series, and most depressant should be reviewed, and it have small samples sizes. Those studies that re- should be considered as a first-line treatment port larger samples (n 25) primarily report if there are no contraindications.
a variety of medications. Only six controlled • Mothers should be provided the information studies (one retrospective,70 five prospec- regarding the known and unknown risks tive42,45,46,54,71) were found that used a variety of controls—some control for depression, while 7. O'Hara MW, Stuart S, Gorman LL, et al. Efficacy of others do not. None of the studies sufficiently interpersonal psychotherapy for postpartum depres- controlled for level of depression. In addition, sion. Arch Gen Psychiatry 2000;57:1039–1045.
8. Appleby L, Warner R, Whitton A, et al. A controlled the case reports are limited by confounding study of fluoxetine and cognitive-behavioral counsel- with in utero exposure, the range of infant ages, ing in the treatment of postnatal depression. BMJ inconsistencies in the timing of when samples were obtained, lack of information about the 9. Murray L, Cooper PJ, Wilson A, et al. Controlled trial amount of medication in foremilk versus of the short- and long-term effect of psychologicaltreatment of post-partum depression: 2. Impact on the hindmilk, and no information about infant con- mother-child relationship and child outcome. Br J Psy- sumption as average breastmilk volumes are not provided. The majority of studies provide 10. Cohen LS, Viguera AC, Bouffard SM, et al. Venlafax- information about the amount of medication ine in the treatment of postpartum depression. J Clin detected in breastmilk and maternal serum.
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the loss of smell in a visual culture susana cámara leret the loss of smell in a visual culture susana cámara leret Fig. 1 smell can provide a new understanding of nature I would like to thank the following people for their support and guidance throughout the project: Rodrigo Camara Leret; Maria Luisa Leret Verdu from the Department of Physiology (Animal Physiology II) University Complutense of Madrid, Spain; Jan Frits Veldkamp PhD from the National Herbarium of the Netherlands; Frans Krens PhD and Maarten A. Jongsma PhD from Plant Breeding International, Wageningen University and Research Center, The Netherlands; Yehuda Shoenfeld, Head of Department of Medicine B and Center for Autoimmune Diseases, Sheba Medical Center, Tel-Aviv, Israel; Professor Fabrizio Benedetti from the Department of Neuroscience, University of Turin Medical School, Italy; Andrea Evers, Investigator Clinical Psychology at the Medisch Centrum Radboud Universiteit Nijmegen, The Netherlands; Dirk Hermans from the Center for the Psychology of Learning and Experimental Psychopathology, University of Leuven, Belgium; Professor Berry M. Spruijt, Ethology and Welfare, Department of Biology, Faculty of Beta Sciences, University of Utrecht, The Netherlands.