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Serum Concentrations of Antidepressants and Benzodiazepines in Nursing Infants: A Case Series Carol S. Birnbaum, MD*; Lee S. Cohen, MD*; Jennie W. Bailey, BA*; Lynn R. Grush, MD*; Laura M. Robertson, BA*; and Zachary N. Stowe, MD‡ ABSTRACT. Objective. The relative risk of psycho- Conclusions. These data support the low incidence of tropic medication use in women with puerperal psychi- infant toxicity and adverse effects associated with anti- atric illness who are breastfeeding has yet to be quanti- depressant and benzodiazepine use during breastfeed- fied adequately. Although the emotional and medical ing. These data also suggest that infant serum monitoring benefits of breastfeeding and adverse effects of maternal is helpful in the assessment of medication exposure in depression on infant development are well described, children of mothers who breastfeed while using psych- how these absolute benefits weigh against the potential otropic medications. Given the limited accumulated data effects of psychotropic drug use during lactation to ulti- regarding serum concentrations of psychotropic medica- mately guide clinical decisions is still unclear. The ob- tions in breastfeeding infants, no single agent seems to jective of this report was to evaluate the extent that be safer than another. Therefore, choice of pharmacologic psychotropic medications were present in the serum of treatment should be guided by the likelihood that it will infants breastfed by mothers treated with antidepres- result in restoration of maternal psychiatric well-being. sants and benzodiazepines. Pediatrics 1999;104(1). URL: http://www.pediatrics.org/ Design. Serum samples were obtained from 35 nurs- cgi/content/full/104/1/e11; breastfeeding, antidepressants, ing infants whose mothers were treated with psycho- benzodiazepines. tropic medications while breastfeeding. When a detect- able concentration of medication was reported, information regarding infant behavior was obtained by ABBREVIATION. SSRI, selective serotonin reuptake inhibitor. maternal report. Setting. The Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital serves as a everal investigators describe a high prevalence regional consultation center for the treatment of psychi- of psychiatric disorders during the postpartum atric disorders during pregnancy and the postpartum pe- period. Major depression, which occurs in riod. S; 10% of postpartum women, is of primary con- Patients. Subjects were mothers referred to the Peri- cern.1,2 In addition, the puerperium may be a time of natal Psychiatry Program for consultation regarding the particular risk for women with a history of mood relative safety of psychotropic medication use while 3,4 breastfeeding. disorder. Anxiety disorders, including panic disor- Primary Outcome Measures. Presence of detectable der and obsessive compulsive disorder, as well as levels of medication in infants whose mothers breastfed postpartum psychosis, are less prevalent but also while taking psychotropic medications during pregnancy may have a significant impact on maternal function- and/or during the puerperium and the well-being (based ing.5,6 The high prevalence of postpartum psychiatric on maternal report) of infants who had detectable serum illness and the extent to which psychotropic medica- concentrations of medication. tions are prescribed to postpartum women under- Results. Seventy-four percent (n 5 26) of infants had serum medication concentrations below the laboratory score the need to develop treatment guidelines for limit of detection (assay sensitivity 5–50 ng/mL). In the women who suffer from psychiatric disorders during remaining 26% of the sample (n 5 9), serum concentra- the postpartum period. For postpartum women who tions of psychotropic medications and/or active metabo- choose to breastfeed, little exists in the way of scien- lites were detected. In each of these cases, infants had tifically derived guidelines that address the use of been exposed to the medication during pregnancy. Med- psychotropic medications during lactation and ap- ications were not detected in infant serum when mothers propriate monitoring of infant serum concentrations had taken these agents solely during the postpartum of psychotropic medication. Nonetheless, postpar- period. No readily apparent difficulties with the infants were reported by mothers. tum women are counseled routinely not to breast- feed when prescribed psychotropic medications. These recommendations are made without data re- From the *Perinatal Psychiatry Program, Massachusetts General Hospital, garding the safety of treatment with a given medi- Harvard Medical School, Boston, Massachusetts; and ‡Pregnancy and Post- cation during breastfeeding or are based on anec- partum Mood Disorders Program, Emory University School of Medicine, Atlanta, Georgia. dotal data that describe symptoms such as colic, Received for publication Sep 11, 1998; accepted Feb 10, 1999. irritability, and sedation in infants whose mothers Reprint requests to (L.S.C.) Perinatal Psychiatry Clinical Research Program, have ingested a particular psychotropic medication Massachusetts General Hospital, 15 Parkman St, WACC 812, Boston, MA while breastfeeding.7,8 Despite these anecdotal re- 02114. E-mail: [email protected] PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- ports, professional guidelines established by the emy of Pediatrics. American Academy of Pediatrics do not preclude the http://www.pediatrics.org/cgi/content/full/104/1/Downloaded from www.aappublications.org/newse11 by guestPEDIATRICS on September 24, Vol. 2021 104 No. 1 July 1999 1of6 use of psychotropic medications in women who untreated maternal illness and the benefits of breastfeeding. When breastfeed.9 mothers elect to take psychotropic medications during lactation, infant monitoring typically includes the determination of infant The positive medical and emotional benefits of serum concentrations of psychotropic medication and is part of 10 breastfeeding are well described. In addition, grow- routine follow-up. ing evidence suggests that untreated maternal mood The current investigation was undertaken after approval by the disorder may have a significant impact on mother– institutional review board at Massachusetts General Hospital. All infant attachment and child development11–13 and participants gave informed verbal consent to participate. Subjects typically were patients of community psychiatrists who were re- may increase the risk for chronic depressive illness in ferred to the Perinatal Psychiatry Program for consultation regard- the mother.14,15 Thus, relative risk assessment in cases ing perinatal psychiatric care. Several subjects were followed pri- of women who wish to breastfeed while using psy- marily by clinicians within the program (L.S.C., C.B., L.G.). All chotropic medications such as antidepressants and patients who were seen by physicians in the program and who elected to breastfeed while taking psychotropic medications were benzodiazepines warrants additional investigation. invited to participate in the study. Of these patients, 10% to 20% Reports of adverse effects after infant exposure to declined because of logistic reasons or refusal to have the infant medications via breast milk are described for a broad undergo venipuncture. range of compounds. Specific reports of antidepres- The concentrations of psychotropic medications and their me- sant treatment during breastfeeding were reviewed tabolites, if any, were measured in serum samples obtained from 16 35 infants of mothers referred to the Perinatal Psychiatry Program by Wisner and associates. These case reports or who elected either 1) to continue pharmacologic therapy begun small uncontrolled case series describe the amount of during pregnancy (n 5 25) or 2) to initiate psychopharmacologic medication present in breast milk or infant serum at treatment during the puerperium (n 5 10). Five infants were a given point in time and associated infant symp- tested on a second occasion either after an increase in maternal 7,17 daily dose of psychotropic medication or in situations in which toms such as colic, irritability, and sedation. These detectable concentrations of psychotropic medications were re- symptoms are offered frequently as examples of tox- ported in an initial sample of infant serum. Serum samples were icity, although symptoms such as colic, irritability, obtained either by antecubital venous sampling or by lateral heel and a range of alertness are also noted in infants stick. Mothers were treated with a number of psychotropic med- 5 5 whose mothers do not breastfeed while taking psy- ications including clomipramine (n 1), desipramine (n 4), imipramine (n 5 2), nortriptyline (n 5 4), fluoxetine (n 5 12), chotropic medications. In addition, the concurrent paroxetine (n 5 2), sertraline (n 5 3), clonazepam (n 5 11), use of nonpsychotropic medications for pain relief or trifluoperazine (n 5 1), and valproic acid (n 5 2). Several of these infection control makes assignment of a causal rela- women (n 5 6) were treated with a combination of psychotropic tionship between maternal use of a psychotropic agents. Infant serum was assayed at 11 different hospital and commu- drug and observed infant symptoms even more nity laboratories, and test results were forwarded to the Perinatal problematic. Psychiatry Program. Sensitivities of assays used in different labo- The extent to which infant exposure to psycho- ratories varied (10–25 ng/mL for tricyclic antidepressants,