Expert: Ivan Goldberg, M.D. - 5/5/2007

Question
Hi Dr. Ivan,
 it is so cool to find that I can ask you a question personally as your website is one of my favorites!

I have Bipolar 1 and am 7 months pregnant.  I have been doing OK so far without my meds, but I fear that I will fall apart post-partem.  I have heard so much about the benefits of breastfeeding and would love to try, but I would also really like to get back on my Lithium, which was the med that seemed to work the best for me. (Depakote also worked but I gained 80 lbs).

Are there any mood stabilizers that you would recommend for women breastfeeding?  I read the abstract you posted; "Mood stabilizers during breastfeeding: a review" by Chaudron and Jefferson.  It looks to me like they all have problems.  Would I be safer bottle feeding? Or just staying off the meds for as long as I can while breast feeding?

Thanks,
 Danielle

Answer
Hi, Danielle . . .

I am delighted that you find Depression Central to be useful.

When it comes to lithium and pregnancy. There is clearly some, but little risk to the fetus if lithium is taken during the first trimester of pregnancy. The actual risk is much less than most people think.

When it comes to breastfeeding I generally advise my patients who have done well on lithium to continue it throughout the period of lactation, unless some difficulty is observed in the infant.

Below you will find some old and new abstracts on the topic. If you want to see the actual articles, the intralibrary loan of your local library should be able to get them for you.

Best regards . . .

Ivan
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1: Am J Psychiatry. 2007 Feb;164(2):342-5.    Related Articles, Links
   Click here to read
   Lithium in breast milk and nursing infants: clinical implications.

   Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfield T, Mogielnicki J, Baldessarini RJ, Zurick A, Cohen LS.

   Perinatal and Reproductive Psychiatry Clinical Research Program, Department of Psychiatry, Massachusetts General Hospital, Simches Research Bldg., Second Fl., Suite 2200, 185 Cambridge St., Boston, MA 02114, USA. aviguera@partners.org

   OBJECTIVE: Current practice guidelines discourage use of lithium during breast-feeding, despite limited data. This study aimed to quantify lithium exposure in nursing infants. METHOD: In 10 mother-infant pairs, the authors obtained assays of lithium in maternal serum, breast milk, and infant serum and indices of infant renal and thyroid function. RESULTS: Maternal serum, breast milk, and infant serum daily trough concentrations of lithium averaged 0.76, 0.35, and 0.16 meq/liter, respectively, each lithium level lower than the preceding level by approximately one-half. No serious adverse events were observed, and elevations of thyroid-stimulating hormone, blood urea nitrogen, and creatinine were few, minor, and transient. CONCLUSIONS: Serum lithium levels in nursing infants were low and well tolerated. No significant adverse clinical or behavioral effects in the infants were noted. These findings encourage reassessment of recommendations against lithium during breast-feeding and underscore the importance of close clinical monitoring of nursing infants.

   Publication Types:

       * Research Support, N.I.H., Extramural
       * Research Support, Non-U.S. Gov't


   PMID: 17267800 [PubMed - indexed for MEDLINE]

2: Encephale. 2006 Mar-Apr;32(2 Pt 1):224-30.    Related Articles, Links

   [Pregnancy, breast feeding and mood stabilisers: review and recommendations for practice]

   [Article in French]

   Even C, Dorocant ES, Thuile J, Kalck-stern M, Guelfi JD.

   Clinique des Maladies Mentales et de l'Encephale, Centre Hospitalier Sainte-Anne, Paris.

   INTRODUCTION: The high prevalence of bipolar affective disorder, the early age of onset and the even sex ratio imply that numerous women of childbearing age raise the question of mood stabilisers during pregnancy and breast feeding. LITERATURE FINDINGS: Some data suggest that giving appropriate answers to bipolar women who want to have children is an unmet need. We reviewed the risks and therapeutic options of this period of life in women with bipolar disorder. The generally accepted idea that pregnancy protects from relapses in bipolar disorders may be untrue and even deceitful. Lithium is the only mood stabiliser that can be prescribed in some cases during the first three months of pregnancy. DISCUSSION AND GUIDE LINES: We give explicit criteria that allow to consider this option: a severe illness prior to lithium prescription, a highly favourable outcome since initiation of lithium, no relapse during the last 18 months. When such conditions are satisfied, a reflection of the patient and at best of the couple must be proposed and associated with very complete information, both oral and written when possible, on the risks and benefits of the interruption and/or continuation of lithium. The teratogenic risks with anticonvulsants have been demonstrated and their prescription during the first three months of pregnancy should be avoided. Besides, there is some concern about the psycho-motor development of children born from women who were under anticonvulsants during pregnancy. The more recent mood stabilisers are not recommended either due to insufficient data. Breast feeding is not recommended under lithium, but seems safe under carbamazepine or valproate and its derivatives.

   Publication Types:

       * English Abstract
       * Review


   PMID: 16910623 [PubMed - indexed for MEDLINE]

3: Bipolar Disord. 2006 Jun;8(3):207-20.    Related Articles, Links
   Click here to read
   Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers.

   Gentile S.

   Department of Mental Health ASL Salerno 1, Operative Unit District n 4, Salerno, Italy. salvatore_gentile@alice.it

   OBJECTIVES: Bipolar disorders are reported to have a high incidence during childbearing years and the need may arise to start or continue a pharmacological treatment during pregnancy and the postpartum period. In the last few years several investigations have evaluated the efficacy of emerging mood-stabilizing agents in the treatment of bipolar disorders, such as lamotrigine, olanzapine, risperidone, quetiapine, aripiprazole and ziprasidone. A number of studies, which examined the use of oxcarbazepine, point to its potential usefulness in prophylactic treatment. The aim of this review is to compare information from the literature on the safety of lamotrigine, oxcarbazepine, risperidone, olanzapine, and quetiapine to the safety data on classic mood stabilizers during pregnancy and the postpartum period. METHODS: A computerized search carried out from 1980 to April 5, 2006 led to the summarization of the results. (References were updated after acceptance and prior to publication.) RESULTS: Emerging mood stabilizers show uncertain safety parameters in pregnancy and lactation. Limited information on lamotrigine and oxcarbazepine does not suggest a clear increase in teratogenicity, while olanzapine appears to be associated with a higher risk of metabolic complications in pregnant women. Data about risperidone and quetiapine are still inconclusive. Finally, the literature on the safety of these compounds in breastfeeding is anecdotal. CONCLUSIONS: Untreated pregnant bipolar women are at an increased risk of poor obstetrical outcomes and relapse of affective symptoms. On the other hand, classic antiepileptic drugs are well-known human teratogens, whereas data on lithium are partially ambiguous. The safety of emerging mood stabilizers in pregnancy and breastfeeding has not been examined extensively. Therefore, when approaching bipolar disorder, if possible, each episode must be considered separately.

   Publication Types:

       * Review


   PMID: 16696822 [PubMed - indexed for MEDLINE]

4: CNS Drugs. 2006;20(3):187-98.    Related Articles, Links

   Use of psychotropic medications in treating mood disorders during lactation : practical recommendations.

   Eberhard-Gran M, Eskild A, Opjordsmoen S.

   Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. malin.eberhard-gran@fhi.no

   Many new mothers who need antidepressant or mood-stabilising drug treatment may wish to breastfeed their infants, but are hesitant to do so because of possible harmful effects of the medication on the infant. This article reviews current data on drug excretion into breast milk and the effects on the breast-fed child, and provides recommendations for the use of the different psychotropic drugs in lactating women.Relevant literature was identified through systematic searches of MEDLINE, EMBASE and the Science Citation Index Expanded (ISI) from 1966 to February 2005. The present knowledge is based on the accumulation of case studies. No randomised controlled trials in breast-fed infants have been performed and there is a lack of long-term follow-up studies.Use of SSRIs and TCAs (except doxepin) is compatible with breastfeeding. However, if treatment with an SSRI is started in the postpartum period, fluoxetine and citalopram may not be drugs of first choice. With regard to other antidepressants, such as venlafaxine, trazodone, mirtazapine, reboxetine, moclobemide and other MAOIs, very little knowledge exists. Breastfeeding should be avoided while using lithium. Carbamazepine and sodium valproate (valproic acid) are generally better tolerated by the breast-fed infant than lithium. Data on lamotrigine are still sparse. Knowledge is also scarce on the novel antipsychotics and thus recommendations in lactating women cannot be made for these agents. It is unwise to expose infants unnecessarily to drugs that may have severe adverse effects. As such, clozapine should probably be avoided because of the risk of agranulocytosis.Our knowledge of the impact of drug exposure through breast milk is still limited. Infant drug exposure is, however, generally higher during pregnancy through placental passage than through breast milk. Despite the low dosage transferred to the infant through breast milk, premature infants and infants with neonatal diseases or inherited disturbances in metabolism may be vulnerable to such exposure.

   Publication Types:

       * Practice Guideline
       * Research Support, Non-U.S. Gov't
       * Review


   PMID: 16529525 [PubMed - indexed for MEDLINE]

5: Can J Clin Pharmacol. 2004 Fall;11(2):e257-66. Epub 2004 Dec 8.    Related Articles, Links
   Click here to read
   When breastfeeding mothers need CNS-acting drugs.

   Rubin ET, Lee A, Ito S.

   Department of Pediatrics, The Hospial for Sick Children, University of Toronto.

   BACKGROUND: Breastfeeding is the ideal method of infant nutrition. However, if mothers need medications such as the central nervous system (CNS) acting drugs, infant safety concerns arise. Summarized information on infant exposure levels to drugs in milk and associated side effect profiles will help clinicians to rationalize and justify important drug therapy for a breastfeeding patient. METHODS: Electronic searches of MEDLINE and PsycINFO from 1966-2003, and of EMBASE from 1980-2003, were conducted for studies on breastfeeding or breast milk and medications in the following categories: antidepressants, antipsychotics, antiepileptics (or anticonvulsants) and anxiolytics. The infant exposure level (%) was defined as follows: [Drug concentration in milk (mg/mL)] x [Daily milk intake (mL/kg/d)] x 100 / Maternal dose (mg/kg/d). RESULTS: A total of 129 papers were eligible for analyses. Our findings indicate that the majority of the CNS-acting drugs, if taken by nursing women, result in average exposure levels to their breast-fed infants of less than 10% of the therapeutic doses per kg body weight. Exceptions are lithium, ethosuximide, phenobarbital, primidone, lamotrigine and topiramate. Adverse effect profiles do not always correlate with a higher exposure level. Overall, most reported adverse effect profiles appear benign. Where adverse effects were reported, they were often confounded by intrauterine exposure. CONCLUSIONS: CNS-acting drugs taken by the mother do not appear to pose any major risks of immediate adverse effects to the breastfeeding infant, although with most of the newer drugs further research is needed to be conclusive.

   Publication Types:

       * Meta-Analysis
       * Research Support, Non-U.S. Gov't


   PMID: 15591613 [PubMed - indexed for MEDLINE]

6: Ther Drug Monit. 2003 Jun;25(3):364-6.    Related Articles, Links
   Click here to read
   Monitoring lithium in breast milk: an individualized approach for breast-feeding mothers.

   Moretti ME, Koren G, Verjee Z, Ito S.

   The Motherisk Program and Division of Clinical Pharmacology, Hospital for Sick Children, Toronto, Ontario, Canada.

   Lithium is a drug of choice for the management of bipolar disorder, a disease frequently affecting women in their childbearing years. Unfortunately, this drug has typically been contraindicated in nursing women. Data in humans are limited with respect to the use of this drug in lactating women, and early reports suggest high excretion into milk. The purpose of this report was to verify the excretion of lithium into human milk and to assess infant safety after breast-feeding. The authors found wide interpatient variability in lithium dose offered to the infant through breast milk (from 0% to 30% of maternal weight-adjusted dose), indicating that therapeutic drug monitoring of lithium in milk and/or in infant's blood, coupled with close monitoring of adverse effects, is a rational approach. Since therapeutic drug monitoring of lithium is routine, physicians caring for these women and infants should be encouraged to individualize their recommendations.

   Publication Types:

       * Research Support, Non-U.S. Gov't
       * Review


   PMID: 12766565 [PubMed - indexed for MEDLINE]

7: J Toxicol Clin Toxicol. 2001;39(4):381-92.    Related Articles, Links

   The effects of lithium, valproic acid, and carbamazepine during pregnancy and lactation.

   Iqbal MM, Sohhan T, Mahmud SZ.

   Department of Psychiatry & Behavioral Neurobiology, The University of Alabama at Birmingham, 35294-0017, USA. miqbal@uabmc.edu

   The chronic, complex, and episodic course of bipolar mood disorder presents a particularly formidable challenge to the clinician making a treatment plan for the onset or recurrence of the illness during pregnancy and lactation. Women treated with anti-manic drugs who become pregnant are commonly considered to be at high risk for fetal complications during the pregnancy or during lactation. The risks of antimanic drug use during pregnancy include teratogenic effects, direct neonatal toxicity, and the potential for longer-term neurobehavioral sequela. The use of medications during pregnancy and lactation requires critical attention to the timing of exposure, dosage, duration of use, and fetal susceptibility. The postnatal period is a time of increased onset and relapse of mental illness. No antimanic drug can be proven completely safe. Prescribing antimanic medications with a long safety record, avoiding exposure in the first trimester; avoiding multidrug regimens, and prescribing the lowest dose for the shortest duration will minimize the fetal risk. This review considers treatment with lithium, valproic acid, and carbamazepine. It assesses the risk to the fetus, the perinatal risks for the infant, the risks associated with treatment during the puerperium and breast-feeding, and the risks to the later development of the child.

   Publication Types:

       * Review


   PMID: 11527233 [PubMed - indexed for MEDLINE]

8: Can Fam Physician. 1999 May;45:1173-5.    Related Articles, Links

   Continuing drug therapy while breastfeeding. Part 2. Common misconceptions of physicians.

   Koren G, Moretti M, Ito S.

   University of Toronto.

   QUESTION: Is there any way to predict whether a drug taken by a mother is safe for a suckling baby, or is it just trial and error? One of my patients is receiving lithium for manic depression. She wishes to breastfeed, but clinically there is no way she can discontinue the drug. My sources say the drug is incompatible with breastfeeding. ANSWER: The amount of drug available to a baby through breastmilk is estimated as the percentage of maternal dose per kg ingested by the baby. Because infants' clearance rate of many drugs is slower than adults', however, the true level of the drug circulating in the infant's blood might be much higher. Because lithium can be measured in plasma, it is prudent to measure it in milk and to estimate the "baby dose." If a baby shows any adverse effects, lithium levels should be measured in its blood.

   Publication Types:

       * Case Reports


   PMID: 10349056 [PubMed - indexed for MEDLINE]

9: J Clin Psychiatry. 1998;59 Suppl 6:57-64; discussion 65.    Related Articles, Links

   The use of lithium and management of women with bipolar disorder during pregnancy and lactation.

   Llewellyn A, Stowe ZN, Strader JR Jr.

   Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.

   The introduction of lithium salts almost a century ago and the subsequent approval of lithium carbonate for the treatment of patients with bipolar disorder represent one of the cornerstones of modern psychopharmacology. The onset of bipolar disorder in women often occurs during the childbearing years, which complicates the treatment decisions secondary to the possibility of conception while taking medication. The establishment of the lithium registry for fetal teratogenesis in the late 1960s ushered in a heightened level of concern for the use of lithium during the reproductive years; although, in the years to come, it has become apparent that alternative pharmacologic treatments for bipolar disorder may exceed the teratogenic risk of lithium monotherapy. In this paper, the available data on the use of antimanic medications during pregnancy and lactation are reviewed with an emphasis on providing a realistic risk/benefit assessment for medication selection and management of these patients. Treatment strategies are discussed for (1) women who are contemplating pregnancy (2) women who inadvertently conceive while taking medications (3) women who choose to become pregnant while taking medication, and (4) women who intend to breastfeed while taking medications.

   Publication Types:

       * Research Support, Non-U.S. Gov't
       * Research Support, U.S. Gov't, P.H.S.
       * Review


   PMID: 9674938 [PubMed - indexed for MEDLINE]

10: J Clin Psychiatry. 1990 Oct;51(10):410-3.    Related Articles, Links

   Lithium treatment during pregnancy, delivery, and lactation: an update.

   Schou M.

   Psychiatric Hospital, Risskov, Denmark.

   Because prophylactic lithium treatment is often given to manic depressive women of fertile age, the answers to five questions are pressing: (1) Does lithium administration during pregnancy expose the unborn child to risk of malformations? (2) Does such exposure lead to later developmental anomalies? (3) Do changes in the pharmacokinetics of lithium during pregnancy and delivery require special precautions? (4) Does lithium treatment during pregnancy exert other effects? (5) Is it advisable that women in lithium treatment breastfeed their infants? The author discusses these questions in the light of present-day knowledge and proposes guidelines for lithium treatment during pregnancy, delivery, and lactation.

   Publication Types:

       * Review


   PMID: 2211538 [PubMed - indexed for MEDLINE]

11: Encephale. 1989 Mar-Apr;15(2):283-6.    Related Articles, Links

   [Lithium, pregnancy and breast feeding]

   [Article in French]

   Villeneuve A, Lajeunesse C, Pires A.

   Departement de Psychiatrie, Faculte de Medecine, Universite Laval, Quebec, Canada.

   Due to its teratogenic potential and its passage in the maternal milk, the administration of lithium during pregnancy and post-partum, if breast-feeding is contemplated, raises specific issues. The kinetics of lithium during pregnancy is reviewed, as well as its influence on the foetus during this period and during breast-feeding. Its teratogenicity affects particularly the cardiovascular system, the Ebstein's anomaly being the most typical and frequent malformation. As a general rule, the administration of lithium should be avoided during pregnancy, at least during the first trimester. However, pregnancy and breast-feeding do not represent an absolute contraindication for the continuation of lithium therapy if it is deemed necessary, in spite of the risks that can be incurred and of which the patient should be informed.

   Publication Types:

       * English Abstract
       * Review


   PMID: 2666104 [PubMed - indexed for MEDLINE]

12: J Clin Psychiatry. 1983 Oct;44(10):358-61.    Related Articles, Links

   The use of lithium during pregnancy and lactation.

   Linden S, Rich CL.

   Because of possible teratogenicity, lithium should be used during the first trimester only if clinically essential. Lithium levels should be monitored throughout pregnancy and dosage adjusted as necessary. Sodium-restricted diets and diuretics should be used with caution. Lithium dose should be reduced with the onset of labor. Mothers who choose to breast-feed should watch for signs of toxicity in their babies. With their consent, pregnant women on lithium should be reported to the American Register of Lithium Babies.

   Publication Types:

       * Review


   PMID: 6358200 [PubMed - indexed for MEDLINE]