Current Psychiatry Reports

, 21:114 | Cite as

Lithium Use and Non-use for Pregnant and Postpartum Women with Bipolar Disorder

  • Alison HermannEmail author
  • Alyson Gorun
  • Abigail Benudis
Bipolar Disorders (R Hirschfeld, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Bipolar Disorders


Purpose of Review

Despite being recognized as a first-line treatment for bipolar disorder, there is still inconsistent use of lithium in perinatal populations. This article will review data regarding lithium use during the peripartum and provide management recommendations for general psychiatric clinicians.

Recent Findings

In contrast to prior data, recent studies indicate that lithium use in pregnancy is associated with either no increased malformations risk or a small increase in risk for cardiac malformations including Ebstein’s anomaly. Limited data also show no significant effect on obstetric or neurodevelopmental outcomes. Data regarding infant lithium exposure via breastmilk remains limited.


Lithium is currently under-prescribed and is an important treatment for women with bipolar disorder in pregnancy and the postpartum. Clinicians must weigh the risk of lithium treatment versus the risk of withholding or changing lithium treatment when managing bipolar disorder in this population.


Lithium Pregnancy Postpartum Psychosis Bipolar Breastfeeding 


Compliance with Ethical Standards

Conflict of Interest

Alyson Gorun and Abigail Benudis each declare no potential conflicts of interest.

Alison Hermann has received personal fees from Sage Therapeutics and a co founder and CMO of Iris OB Health.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gentile S. Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers. Bipolar Disord. 2006;8(3):207–20. Scholar
  2. 2.
    Reich T, Winokur G. Postpartum psychoses in patients with manic depressive disease. J Nerv Ment Dis. 1970;151(1):60–8. Scholar
  3. 3.
    van Gent EM, Verhoeven WM. Bipolar illness, lithium prophylaxis, and pregnancy. Pharmacopsychiatry. 1992;25(4):187–91. Scholar
  4. 4.
    Wisner KL, Hanusa BH, Peindl KS, Perel JM. Prevention of postpartum episodes in women with bipolar disorder. Biol Psychiatry. 2004;56(8):592–6. Scholar
  5. 5.
    ••Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, et al. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164(12):1817–24; quiz 923. This prospective observational cohort study found that there was a much higher risk of recurrence of a mood episode for bipolar women who discontinued treatment with mood stabilizers as compared to those who continued it. These mood episodes were more likely to be depressive or mixed and early in pregnancy. CrossRefGoogle Scholar
  6. 6.
    Maina G, Rosso G, Aguglia A, Bogetto F. Recurrence rates of bipolar disorder during the postpartum period: a study on 276 medication-free Italian women. Arch Womens Ment Health. 2014;17(5):367–72. Scholar
  7. 7.
    Wesseloo R, Kamperman AM, Munk-Olsen T, Pop VJ, Kushner SA, Bergink V. Risk of postpartum relapse in bipolar disorder and postpartum psychosis: a systematic review and meta-analysis. Am J Psychiatry. 2016;173(2):117–27. Scholar
  8. 8.
    Grunze H, Vieta E, Goodwin GM, Bowden C, Licht RW, Moller HJ, et al. The world Federation of Societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2012 on the long-term treatment of bipolar disorder. World J Biol Psychiatry. 2013;14(3):154–219. Scholar
  9. 9.
    Geddes JR, Miklowitz DJ. Treatment of bipolar disorder. Lancet. 2013;381(9878):1672–82. Scholar
  10. 10.
    Bjorklund L, Horsdal HT, Mors O, Ostergaard SD, Gasse C. Trends in the psychopharmacological treatment of bipolar disorder: a nationwide register-based study. Acta Neuropsychiatr. 2016;28(2):75–84. Scholar
  11. 11.
    Broeks SC, Thisted Horsdal H, Glejsted Ingstrup K, Gasse C. Psychopharmacological drug utilization patterns in pregnant women with bipolar disorder - a nationwide register-based study. J Affect Disord. 2017;210:158–65. Scholar
  12. 12.
    McCrea RL, Nazareth I, Evans SJ, Osborn DP, Pinfold V, Cowen PJ, et al. Lithium prescribing during pregnancy: a UK primary care database study. PLoS One. 2015;10(3):e0121024. Scholar
  13. 13.
    Larsen ER, Damkier P, Pedersen LH, Fenger-Gron J, Mikkelsen RL, Nielsen RE, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;445:1–28. Scholar
  14. 14.
    Weinstein MR, Goldfield M. Cardiovascular malformations with lithium use during pregnancy. Am J Psychiatry. 1975;132(5):529–31. Scholar
  15. 15.
    Goldfield M, Weinstein MR. Lithium in pregnancy: a review with recommendations. Am J Psychiatry. 1971;127(7):888–93. Scholar
  16. 16.
    Nora JJ, Nora AH, Toews WH. Letter: Lithium, Ebstein's anomaly, and other congenital heart defects. Lancet. 1974;2(7880):594–5. Scholar
  17. 17.
    Gruber MF, The US. FDA pregnancy lactation and labeling rule - implications for maternal immunization. Vaccine. 2015;33(47):6499–500. Scholar
  18. 18.
    Clark CT, Wisner KL. Treatment of Peripartum bipolar disorder. Obstet Gynecol Clin N Am. 2018;45(3):403–17. Scholar
  19. 19.
    Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, et al. Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry. 2004;161(4):608–20. Scholar
  20. 20.
    Osborne LM. Recognizing and managing postpartum psychosis: a clinical guide for obstetric providers. Obstet Gynecol Clin N Am. 2018;45(3):455–68. Scholar
  21. 21.
    ••Poels EMP, Bijma HH, Galbally M, Bergink V. Lithium during pregnancy and after delivery: a review. Int J Bipolar Disord. 2018;6(1):26. Comprehensive review article with recommendations for lithium use during pregnancy and postpartum. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kendell RE, Chalmers JC, Platz C. Epidemiology of puerperal psychoses. Br J Psychiatry. 1987;150:662–73. Scholar
  23. 23.
    Grof P, Robbins W, Alda M, Berghoefer A, Vojtechovsky M, Nilsson A, et al. Protective effect of pregnancy in women with lithium-responsive bipolar disorder. J Affect Disord. 2000;61(1–2):31–9.CrossRefGoogle Scholar
  24. 24.
    •Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ. Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry. 2000;157(2):179–84. Retrospective study comparing mood episode recurrence after lithium discontinuation in women with bipolar disorder during pregnancy and postpartum to age-matched nonpregnant women. Their results showed that rates of mood episode recurrence were similar in the first 40 weeks after lithium discontinuation but postpartum recurrences were 2.9 times more likely in pregnant women in the postpartum period versus equivalent time period in nonpregnant women. CrossRefPubMedGoogle Scholar
  25. 25.
    Baldessarini RJ, Tondo L, Viguera AC. Discontinuing lithium maintenance treatment in bipolar disorders: risks and implications. Bipolar Disord. 1999;1(1):17–24.CrossRefGoogle Scholar
  26. 26.
    Llewellyn A, Stowe ZN, Strader JR Jr. The use of lithium and management of women with bipolar disorder during pregnancy and lactation. J Clin Psychiatry. 1998;59(Suppl 6):57–64 discussion 5.PubMedGoogle Scholar
  27. 27.
    Stevens A, Goossens PJJ, der Klein EAM K-v, Draisma S, Honig A, Kupka RW. Risk of recurrence of mood disorders during pregnancy and the impact of medication: a systematic review. J Affect Disord. 2019;249:96–103. Scholar
  28. 28.
    Nguyen TN, Faulkner D, Frayne JS, Allen S, Hauck YL, Rock D, et al. Obstetric and neonatal outcomes of pregnant women with severe mental illness at a specialist antenatal clinic. Med J Aust. 2013;199(3 Suppl):S26–9.Google Scholar
  29. 29.
    Orsolini L, Valchera A, Vecchiotti R, Tomasetti C, Iasevoli F, Fornaro M, et al. Suicide during perinatal period: epidemiology, risk factors, and clinical correlates. Front Psychiatry. 2016;7:138.
  30. 30.
    Taylor CL, van Ravesteyn LM, denBerg MP V, Stewart RJ, Howard LM. The prevalence and correlates of self-harm in pregnant women with psychotic disorder and bipolar disorder. Arch Womens Ment Health. 2016;19(5):909–15. Scholar
  31. 31.
    Jablensky AV, Morgan V, Zubrick SR, Bower C, Yellachich LA. Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am J Psychiatry. 2005;162(1):79–91. Scholar
  32. 32.
    Lee HC, Lin HC. Maternal bipolar disorder increased low birthweight and preterm births: a nationwide population-based study. J Affect Disord. 2010;121(1–2):100–5. Scholar
  33. 33.
    Khan SJ, Fersh ME, Ernst C, Klipstein K, Albertini ES, Lusskin SI. Bipolar disorder in pregnancy and postpartum: principles of management. Curr Psychiatry Rep. 2016;18(2):13. Scholar
  34. 34.
    MacCabe JH, Martinsson L, Lichtenstein P, Nilsson E, Cnattingius S, Murray RM, et al. Adverse pregnancy outcomes in mothers with affective psychosis. Bipolar Disord. 2007;9(3):305–9. Scholar
  35. 35.
    Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet. 2014;384(9956):1789–99. Scholar
  36. 36.
    Munk-Olsen T, Laursen TM, Mendelson T, Pedersen CB, Mors O, Mortensen PB. Risks and predictors of readmission for a mental disorder during the postpartum period. Arch Gen Psychiatry. 2009;66(2):189–95. Scholar
  37. 37.
    Jones I, Craddock N. Bipolar disorder and childbirth: the importance of recognising risk. Br J Psychiatry. 2005;186:453–4. Scholar
  38. 38.
    Di Florio A, Forty L, Gordon-Smith K, Heron J, Jones L, Craddock N, et al. Perinatal episodes across the mood disorder spectrum. JAMA Psychiatry. 2013;70(2):168–75. Scholar
  39. 39.
    Di Florio A, Gordon-Smith K, Forty L, Kosorok MR, Fraser C, Perry A, et al. Stratification of the risk of bipolar disorder recurrences in pregnancy and postpartum. Br J Psychiatry. 2018;213(3):542–7. Scholar
  40. 40.
    Di Florio A, Smith S, Jones I. Postpartum psychosis. Obstetrician Gynaecol. 2013;15(3):145–50. Scholar
  41. 41.
    ••Bergink V, Burgerhout KM, Koorengevel KM, Kamperman AM, Hoogendijk WJ, Lambregtse-van den Berg MP, et al. Treatment of psychosis and mania in the postpartum period. Am J Psychiatry. 2015;172(2):115–23. The authors outline a specific treatment algorithm for first-onset postpartum psychosis or mania including treatment response and remission outcomes at 9 months postpartum. A significantly lower rate of relapse occurred with lithium use versus antipsychotic monotherapy. CrossRefPubMedGoogle Scholar
  42. 42.
    Pariser SF. Women and mood disorders. Menarche to menopause Ann Clin Psychiatry. 1993;5(4):249–54.CrossRefGoogle Scholar
  43. 43.
    Spinelli MG. Maternal infanticide associated with mental illness: prevention and the promise of saved lives. Am J Psychiatry. 2004;161(9):1548–57. Scholar
  44. 44.
    McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8. Scholar
  45. 45.
    ••Diav-Citrin O, Shechtman S, Tahover E, Finkel-Pekarsky V, Arnon J, Kennedy D, et al. Pregnancy outcome following in utero exposure to lithium: a prospective, comparative, observational study. Am J Psychiatry. 2014;171(7):785–94. This prospective comparative observational study compared lithium exposed pregnancies to disease-matched nonteratogenic-exposed pregnancies and found no difference in major malformations, including cardiovascular, after exluding cardiovascular malformations that spontaneously resolved. CrossRefPubMedGoogle Scholar
  46. 46.
    ••Patorno E, Huybrechts KF, Bateman BT, Cohen JM, Desai RJ, Mogun H, et al. Lithium Use in Pregnancy and the Risk of Cardiac Malformations. N Engl J Med. 2017;376(23):2245–54. This large registry cohort study showed a dose-dependent increased risk of cardiovascular malformations with first trimester lithium exposure as well as increased risk for right ventricular outflow tract obstruction, though this risk is lower than previously described (.6 per 100 live births for exposed compared to .18 per 100 among unexposed). CrossRefGoogle Scholar
  47. 47.
    ••Munk-Olsen T, Liu X, Viktorin A, Brown HK, Di Florio A, D’Onofrio BM, et al. Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies. Lancet Psychiatry. 2018;5(8):644–52. Large international meta-analysis found a small increase risk in congenital malformations but no increase in cardiovascular malformations, though it lacks the power to correlate lithium use to this rare adverse event. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen LS, Stowe ZN. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry. 2005;162(11):2162–70. Scholar
  49. 49.
    Frassetto F, Tourneur Martel F, Barjhoux CE, Villier C, Bot BL, Vincent F. Goiter in a newborn exposed to lithium in utero. Ann Pharmacother. 2002;36(11):1745–8. Scholar
  50. 50.
    Krause S, Ebbesen F, Lange AP. Polyhydramnios with maternal lithium treatment. Obstet Gynecol. 1990;75(3 Pt 2):504–6.PubMedGoogle Scholar
  51. 51.
    Grandjean EM, Aubry JM. Lithium: updated human knowledge using an evidence-based approach: part III: clinical safety. CNS Drugs. 2009;23(5):397–418. Scholar
  52. 52.
    Kozma C. Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. Am J Med Genet A. 2005;132a(4):441–4. Scholar
  53. 53.
    Boden R, Lundgren M, Brandt L, Reutfors J, Andersen M, Kieler H. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. Bmj. 2012;345:e7085. Scholar
  54. 54.
    Frayne J, Nguyen T, Mok T, Hauck Y, Liira H. Lithium exposure during pregnancy: outcomes for women who attended a specialist antenatal clinic. J Psychosom Obstet Gynaecol. 2018;39(3):211–9. Scholar
  55. 55.
    Wisner KL, Sit D, O'Shea K, Bogen DL, Clark CT, Pinheiro E, et al. Bipolar disorder and psychotropic medication: impact on pregnancy and neonatal outcomes. J Affect Disord. 2019;243:220–5. Scholar
  56. 56.
    Cohen JM, Huybrechts KF, Patorno E, Desai RJ, Mogun H, Bateman BT, et al. Anticonvulsant Mood Stabilizer and Lithium Use and Risk of Adverse Pregnancy Outcomes. J Clin Psychiatry. 2019;80(4).
  57. 57.
    Feldman M. Lithium and pregnancy. Isr J Psychiatry Relat Sci. 2008;45(4):300–1 author reply 1.PubMedGoogle Scholar
  58. 58.
    van der Lugt NM, van de Maat JS, van Kamp IL, Knoppert-van der Klein EA, Hovens JG, Walther FJ. Fetal, neonatal and developmental outcomes of lithium-exposed pregnancies. Early Hum Dev. 2012;88(6):375–8. Scholar
  59. 59.
    Schou M. What happened later to the lithium babies? A follow-up study of children born without malformations. Acta Psychiatr Scand. 1976;54(3):193–7.CrossRefGoogle Scholar
  60. 60.
    Jacobson SJ, Jones K, Johnson K, Ceolin L, Kaur P, Sahn D, et al. Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester. Lancet. 1992;339(8792):530–3. Scholar
  61. 61.
    Forsberg L, Adler M, Romer Ek I, Ljungdahl M, Naver L, Gustafsson LL, et al. Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood. Acta Paediatr. 2018;107(8):1379–88. Scholar
  62. 62.
    Poels EMP, Schrijver L, Kamperman AM, Hillegers MHJ, Hoogendijk WJG, Kushner SA, et al. Long-term neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics: a systematic review and meta-analysis. Eur Child Adolesc Psychiatry. 2018;27(9):1209–30. Scholar
  63. 63.
    Horton S, Tuerk A, Cook D, Cook J, Dhurjati P. Maximum recommended dosage of Lithium for pregnant women based on a PBPK model for Lithium absorption. Adv Bioinforma. 2012;2012:352729. Scholar
  64. 64.
    Gentile S. Lithium in pregnancy: the need to treat, the duty to ensure safety. Expert Opin Drug Saf. 2012;11(3):425–37. Scholar
  65. 65.
    ••Wesseloo R, Wierdsma AI, van Kamp IL, Munk-Olsen T, Hoogendijk WJG, Kushner SA, et al. Lithium dosing strategies during pregnancy and the postpartum period. Br J Psychiatry. 2017;211(1):31–6. This retrospective observational cohort study measured lithium levels in pregnant and postpartum women and gives specific guidelines regarding obtaining lithium levels based on this. CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Westin AA, Brekke M, Molden E, Skogvoll E, Aadal M, Spigset O. Changes in drug disposition of lithium during pregnancy: a retrospective observational study of patient data from two routine therapeutic drug monitoring services in Norway. BMJ Open. 2017;7(3):e015738. Scholar
  67. 67.
    Deligiannidis KM. Therapeutic drug monitoring in pregnant and postpartum women: recommendations for SSRIs, lamotrigine, and lithium. J Clin Psychiatry. 2010;71(5):649–50. Scholar
  68. 68.
    Ward S, Wisner KL. Collaborative management of women with bipolar disorder during pregnancy and postpartum: pharmacologic considerations. J Midwifery Womens Health. 2007;52(1):3–13. Scholar
  69. 69.
    Galbally M, Roberts M, Buist A. Mood stabilizers in pregnancy: a systematic review. Aust N Z J Psychiatry. 2010;44(11):967–77. Scholar
  70. 70.
    Deligiannidis KM, Byatt N, Freeman MP. Pharmacotherapy for mood disorders in pregnancy: a review of pharmacokinetic changes and clinical recommendations for therapeutic drug monitoring. J Clin Psychopharmacol. 2014;34(2):244–55. Scholar
  71. 71.
    •Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfield T, Mogielnicki J, et al. Lithium in breast milk and nursing infants: clinical implications. Am J Psychiatry. 2007;164(2):342–5. This study measured serum lithium levels in nursing infants in 10 mother-infant pairs and found no significant adverse events. CrossRefPubMedGoogle Scholar
  72. 72.
    Galbally M, Bergink V, Vigod SN, Buist A, Boyce P, Chandra P, et al. Breastfeeding and lithium: is breast always best? Lancet Psychiatry. 2018;5(7):534–6. Scholar
  73. 73.
    Bogen DL, Sit D, Genovese A, Wisner KL. Three cases of lithium exposure and exclusive breastfeeding. Arch Womens Ment Health. 2012;15(1):69–72. Scholar
  74. 74.
    Frew JR. Psychopharmacology of bipolar I disorder during lactation: a case report of the use of lithium and aripiprazole in a nursing mother. Arch Womens Ment Health. 2015;18(1):135–6. Scholar
  75. 75.
    Moretti ME, Koren G, Verjee Z, Ito S. Monitoring lithium in breast milk: an individualized approach for breast-feeding mothers. Ther Drug Monit. 2003;25(3):364–6.CrossRefGoogle Scholar
  76. 76.
    Perlman CA, Johnson SL, Mellman TA. The prospective impact of sleep duration on depression and mania. Bipolar Disord. 2006;8(3):271–4. Scholar
  77. 77.
    Pacchiarotti I, Leon-Caballero J, Murru A, Verdolini N, Furio MA, Pancheri C, et al. Mood stabilizers and antipsychotics during breastfeeding: focus on bipolar disorder. Eur Neuropsychopharmacol. 2016;26(10):1562–78. Scholar
  78. 78.
    Wesseloo R, Liu X, Clark CT, Kushner SA, Munk-Olsen T, Bergink V. Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: a population-based cohort study. J Affect Disord. 2017;218:394–7. Scholar
  79. 79.
    Bergink V, Rasgon N, Wisner KL. Postpartum psychosis: madness, mania, and melancholia in motherhood. Am J Psychiatry. 2016;173(12):1179–88. Scholar
  80. 80.
    ••Bergink V, Bouvy PF, Vervoort JS, Koorengevel KM, Steegers EA, Kushner SA. Prevention of postpartum psychosis and mania in women at high risk. Am J Psychiatry. 2012;169(6):609–15. This study provides recommendations that women with a history of postpartum psychosis limited to the postpartum period should have medication prophylaxis immediately in the postpartum to reduce the risk of relapse of a mood episode, while women with bipolar disorder require medication prophylaxis throughout pregnancy. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PsychiatryWeill Cornell Medical CenterNew YorkUSA
  2. 2.Department of PsychiatryColumbia University Medical CenterNew YorkUSA

Personalised recommendations