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Weighing the Risks: the Management of Bipolar Disorder During Pregnancy

  • Bipolar Disorders (R Hirschfeld, Section Editor)
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Abstract

Purpose of Review

The management of bipolar disorder during pregnancy requires difficult treatment decisions be made by both women and their clinicians. There is little consensus on management despite the high prevalence of bipolar disorder in reproductive-aged women. In this review, we have summarized the available literature and discuss the balancing of risks associated with treatment decisions.

Recent Findings

Cohort studies have shown a high relapse rate in women with bipolar disorder who discontinue mood-stabilizing medications. The risks of fetal medication exposure have been assessed in multiple database studies.

Summary

Management decisions of bipolar disorder in pregnancy have been made difficult by inconsistencies in study outcomes. There were many confounding factors in the studies of medication discontinuation relapse risk. Inconsistencies in the findings of fetal risks from mood-stabilizing medications have further complicated management decisions. Larger studies are needed to clarify the risks of bipolar disorder relapse in pregnancy with and without treatment.

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References

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

  1. Pedersen CB, Mors O, Bertelsen A, Waltoft BL, Agerbo E, McGrath JJ, et al. A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry. 2014;71(5):573–81. https://doi.org/10.1001/jamapsychiatry.2014.16.

    Article  PubMed  Google Scholar 

  2. Sit D. Women and bipolar disorder across the life span. J Am Med Womens Assoc. 2004;59(2):91–100.

    Google Scholar 

  3. 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(nov07 6):e7085. https://doi.org/10.1136/bmj.e7085.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sharma V, Sharma S. Peripartum management of bipolar disorder: what do the latest guidelines recommend? Expert Rev Neurother. 2016;17:1–10.

    Google Scholar 

  5. • 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. This study showed comparable rates of postpartum bipolar disorder relapses following lamotrigine or lithium use during pregnancy.

    Article  CAS  PubMed  Google Scholar 

  6. 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. https://doi.org/10.1176/appi.ajp.2007.06101639.

    Article  PubMed  Google Scholar 

  7. Newport DJ, Stowe ZN, Viguera AC, Calamaras MR, Juric S, Knight B, et al. Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord. 2008;10(3):432–6. https://doi.org/10.1111/j.1399-5618.2007.00565.x.

    Article  CAS  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. 2007;64(5):543–52. https://doi.org/10.1001/archpsyc.64.5.543.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Merrill L, Mittal L, Nicoloro J, Caiozzo C, Maciejewski PK, Miller LJ. Screening for bipolar disorder during pregnancy. Arch Womens Ment Health. 2015;18(4):579–83. https://doi.org/10.1007/s00737-015-0527-y.

    Article  PubMed  Google Scholar 

  11. Munk-Olsen T, Laursen TM, Pedersen CB, Mors O, Mortensen PB. New parents and mental disorders: a population-based register study. JAMA. 2006;296(21):2582–9. https://doi.org/10.1001/jama.296.21.2582.

    Article  CAS  PubMed  Google Scholar 

  12. Brummelte S, Galea LA. Postpartum depression: etiology, treatment and consequences for maternal care. Horm Behav. 2016;77:153–66.

    Article  PubMed  Google Scholar 

  13. Viguera AC, Cohen LS, Bouffard S, Whitfield TH, Baldessarini RJ. Reproductive decisions by women with bipolar disorder after prepregnancy psychiatric consultation. Am J Psychiatry. 2002;159(12):2102–4. https://doi.org/10.1176/appi.ajp.159.12.2102.

    Article  PubMed  Google Scholar 

  14. Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S, et al. Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. Am J Psychiatry. 2007;164(8):1214–20. https://doi.org/10.1176/appi.ajp.2007.06111886.

    Article  PubMed  Google Scholar 

  15. Greene ND, Copp AJ. Development of the vertebrate central nervous system: formation of the neural tube. Prenat Diagn. 2009;29(4):303–11. https://doi.org/10.1002/pd.2206.

    Article  CAS  PubMed  Google Scholar 

  16. Delgado-Escueta AV, Janz D. Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy. Neurology. 1992;42(4 Suppl 5):149–60.

    CAS  PubMed  Google Scholar 

  17. Ban L, Fleming KM, Doyle P, Smeeth L, Hubbard RB, Fiaschi L, et al. Congenital anomalies in children of mothers taking antiepileptic drugs with and without periconceptional high dose folic acid use: a population-based cohort study. PLoS One. 2015;10(7):e0131130. https://doi.org/10.1371/journal.pone.0131130.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Toriello HV. Policy statement on folic acid and neural tube defects. Genet Med. 2011;13(6):593–6. https://doi.org/10.1097/GIM.0b013e31821d4188.

    Article  PubMed  Google Scholar 

  19. Leong C, Raymond C, Chateau D, Dahl M, Alessi-Severini S, Falk J, et al. Psychotropic drug use before, during, and after pregnancy: a population-based study in a Canadian cohort (2001-2013). Can J Psychiatr. 2017;62(8):543–50. https://doi.org/10.1177/0706743717711168.

    Article  Google Scholar 

  20. Ghouse AA, Sanches M, Zunta-Soares G, Swann AC, Soares JC. Overdiagnosis of bipolar disorder: a critical analysis of the literature. ScientificWorldJournal. 2013;2013:297087.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Smith DJ, Ghaemi N. Is underdiagnosis the main pitfall when diagnosing bipolar disorder? Yes. BMJ. 2010;340(feb22 1):c854. https://doi.org/10.1136/bmj.c854.

    Article  PubMed  Google Scholar 

  22. Peselow ED, Naghdechi L, Pizano D, IsHak WW. Polypharmacy in maintenance of bipolar disorder. Clin Neuropharmacol. 2016;39(3):132–4. https://doi.org/10.1097/WNF.0000000000000147.

    Article  CAS  PubMed  Google Scholar 

  23. Holmes LB, Mittendorf R, Shen A, Smith CR, Hernandez-Diaz S. Fetal effects of anticonvulsant polytherapies: different risks from different drug combinations. Arch Neurol. 2011;68(10):1275–81. https://doi.org/10.1001/archneurol.2011.133.

    Article  PubMed  Google Scholar 

  24. Sadowski A, Todorow M, Yazdani Brojeni P, Koren G, Nulman I. Pregnancy outcomes following maternal exposure to second-generation antipsychotics given with other psychotropic drugs: a cohort study. BMJ Open. 2013;3(7):e003062. https://doi.org/10.1136/bmjopen-2013-003062.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord. 2013;15(1):1–44. https://doi.org/10.1111/bdi.12025.

    Article  CAS  PubMed  Google Scholar 

  26. Schneck CD, Miklowitz DJ, Miyahara S, Araga M, Wisniewski S, Gyulai L, et al. The prospective course of rapid-cycling bipolar disorder: findings from the STEP-BD. Am J Psychiatry. 2008;165(3):370–7: quiz 410. https://doi.org/10.1176/appi.ajp.2007.05081484.

    Article  PubMed  Google Scholar 

  27. Ghaemi SN, Boiman EE, Goodwin FK. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. J Clin Psychiatry. 2000;61(10):804–8: quiz 9. https://doi.org/10.4088/JCP.v61n1013.

    Article  CAS  PubMed  Google Scholar 

  28. Valenti M, Pacchiarotti I, Rosa AR, Bonnin CM, Popovic D, Nivoli AM, et al. Bipolar mixed episodes and antidepressants: a cohort study of bipolar I disorder patients. Bipolar Disord. 2011;13(2):145–54. https://doi.org/10.1111/j.1399-5618.2011.00908.x.

    Article  PubMed  Google Scholar 

  29. Liu X, Agerbo E, Ingstrup KG, Musliner K, Meltzer-Brody S, Bergink V, et al. Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study. BMJ. 2017;358:j3668.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Driscoll KE, Sit DKY, Moses-Kolko EL, Pinheiro E, Yang A, Ciolino JD, et al. Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study. Bipolar Disord. 2017;19(4):295–304. https://doi.org/10.1111/bdi.12500.

    Article  CAS  PubMed  Google Scholar 

  31. Provencher MD, Hawke LD, Thienot E. Psychotherapies for comorbid anxiety in bipolar spectrum disorders. J Affect Disord. 2011;133(3):371–80. https://doi.org/10.1016/j.jad.2010.10.040.

    Article  PubMed  Google Scholar 

  32. Mazza M, Mandelli L, Di Nicola M, Harnic D, Catalano V, Tedeschi D, et al. Clinical features, response to treatment and functional outcome of bipolar disorder patients with and without co-occurring substance use disorder: 1-year follow-up. J Affect Disord. 2009;115(1–2):27–35. https://doi.org/10.1016/j.jad.2008.08.019.

    Article  PubMed  Google Scholar 

  33. Diaz FJ, James D, Botts S, Maw L, Susce MT, de Leon J. Tobacco smoking behaviors in bipolar disorder: a comparison of the general population, schizophrenia, and major depression. Bipolar Disord. 2009;11(2):154–65. https://doi.org/10.1111/j.1399-5618.2009.00664.x.

    Article  PubMed  Google Scholar 

  34. Sharma V, Pope CJ. Pregnancy and bipolar disorder: a systematic review. J Clin Psychiatry. 2012;73(11):1447–55. https://doi.org/10.4088/JCP.11r07499.

    Article  PubMed  Google Scholar 

  35. 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. https://doi.org/10.1016/S0165-0327(99)00197-4.

    Article  CAS  PubMed  Google Scholar 

  36. •• 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. This recent meta-analysis shows the high rate of postpartum relapse that occurs in women with bipolar disorder. In this study, women who continuned maintenance medications or started prophylactic medications immediately following childbirth had a much lower relapse rate than women who remained medication-free.

    Article  PubMed  Google Scholar 

  37. Veroniki AA, Rios P, Cogo E, Straus SE, Finkelstein Y, Kealey R, et al. Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis. BMJ Open. 2017;7(7):e017248. https://doi.org/10.1136/bmjopen-2017-017248.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Rasmussen MH, Strom M, Wohlfahrt J, Videbech P, Melbye M. Risk, treatment duration, and recurrence risk of postpartum affective disorder in women with no prior psychiatric history: a population-based cohort study. PLoS Med. 2017;14(9):e1002392. https://doi.org/10.1371/journal.pmed.1002392.

    Article  PubMed  PubMed Central  Google Scholar 

  39. National Institute for Health and Excellence Care. Antenatal and postnatal mental health 2016 https://www.nice.org.uk/guidance/qs115/resources/antenatal-and-postnatal-mental-health-75545299789765. Accessed 23 Sep 2017.

  40. Rosso G, Albert U, Di Salvo G, Scata M, Todros T, Maina G. Lithium prophylaxis during pregnancy and the postpartum period in women with lithium-responsive bipolar I disorder. Arch Womens Ment Health. 2016;19(2):429–32. https://doi.org/10.1007/s00737-016-0601-0.

    Article  PubMed  Google Scholar 

  41. Cohen LS, Sichel DA, Robertson LM, Heckscher E, Rosenbaum JF. Postpartum prophylaxis for women with bipolar disorder. Am J Psychiatry. 1995;152(11):1641–5. https://doi.org/10.1176/ajp.152.11.1641.

    Article  CAS  PubMed  Google Scholar 

  42. 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. https://doi.org/10.1176/appi.ajp.2012.11071047.

    Article  PubMed  Google Scholar 

  43. Nora JJ, Nora AH, Toews WH. Letter: Lithium, Ebstein's anomaly, and other congenital heart defects. Lancet. 1974;2(7880):594–5.

    Article  CAS  PubMed  Google Scholar 

  44. Cohen LS, Friedman JM, Jefferson JW, Johnson EM, Weiner ML. A reevaluation of risk of in utero exposure to lithium. JAMA. 1994;271(2):146–50. https://doi.org/10.1001/jama.1994.03510260078033.

    Article  CAS  PubMed  Google Scholar 

  45. • Patorno E, Huybrechts KF, Hernandez-Diaz S, et al. N Engl J Med. 2017;377:893–4. This large cohort study demonstrated an increased risk of cardiac defects following in utero lithium exposure. However, the rate of cardiac defects found in this study was much lower than that seen in previous studies.

    Article  PubMed  Google Scholar 

  46. 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. https://doi.org/10.1176/appi.ajp.2014.12111402.

    Article  PubMed  Google Scholar 

  47. Di Florio A, Munk-Olsen T, Bergink V, et al. N Engl J Med. 2017;377:893.

    Article  PubMed  Google Scholar 

  48. Holmes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL, et al. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology. 2008;70(22 Pt 2):2152–8. https://doi.org/10.1212/01.wnl.0000304343.45104.d6.

    Article  CAS  PubMed  Google Scholar 

  49. Deligiannidis KM. Therapeutic drug monitoring in pregnant and postpartum women: recommendations for SSRIs, lamotrigine, and lithium. J Clin Psychiatry. 2010;71(5):649–50. https://doi.org/10.4088/JCP.10ac06132gre.

    Article  CAS  PubMed  Google Scholar 

  50. Benoit R. Does lithium exposure warrant referral for fetal echocardiogram? Am J Obstet Gynecol. 2004;191(6):S127.

    Google Scholar 

  51. Uguz F, Sharma V. Mood stabilizers during breastfeeding: a systematic review of the recent literature. Bipolar Disord. 2016;18(4):325–33. https://doi.org/10.1111/bdi.12398.

    Article  PubMed  Google Scholar 

  52. • Pariente G, Leibson T, Shulman T, Adams-Webber T, Barzilay E, Nulman I. Pregnancy outcomes following in utero exposure to lamotrigine: a systematic review and meta-analysis. CNS Drugs. 2017;31(6):439–50. This systematic review and meta-analysis summarizes the safety data for lamotrigine use in pregnancy.

    Article  CAS  PubMed  Google Scholar 

  53. Chisolm MS, Payne JL. Management of psychotropic drugs during pregnancy. BMJ. 2016;532:h5918.

    Article  PubMed  Google Scholar 

  54. Dolk H, Jentink J, Loane M, Morris J, de Jong-van den Berg LT. Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations? Neurology. 2008;71(10):714–22. https://doi.org/10.1212/01.wnl.0000316194.98475.d8.

    Article  CAS  PubMed  Google Scholar 

  55. Uguz F. Prophylactic use of olanzapine and quetiapine from pregnancy to the postpartum period in women with bipolar disorder: a case series. J Matern Fetal Neonatal Med. 2017;30(21):2569–71. https://doi.org/10.1080/14767058.2016.1256991.

    Article  CAS  PubMed  Google Scholar 

  56. Persson M, Cnattingius S, Villamor E, Soderling J, Pasternak B, Stephansson O, et al. Risk of major congenital malformations in relation to maternal overweight and obesity severity: cohort study of 1.2 million singletons. BMJ. 2017;357:j2563.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Thomson M, Sharma V. Therapeutics of postpartum depression. Expert Rev Neurother. 2017;17(5):495–507. https://doi.org/10.1080/14737175.2017.1265888.

    Article  CAS  PubMed  Google Scholar 

  58. Fisher SD, Wisner KL, Clark CT, Sit DK, Luther JF, Wisniewski S. Factors associated with onset timing, symptoms, and severity of depression identified in the postpartum period. J Affect Disord. 2016;203:111–20. https://doi.org/10.1016/j.jad.2016.05.063.

    Article  PubMed  Google Scholar 

  59. Sharma V, Xie B. Screening for postpartum bipolar disorder: validation of the mood disorder questionnaire. J Affect Disord. 2011;131(1–3):408–11. https://doi.org/10.1016/j.jad.2010.11.026.

    Article  PubMed  Google Scholar 

  60. Frey BN, Simpson W, Wright L, Steiner M. Sensitivity and specificity of the mood disorder questionnaire as a screening tool for bipolar disorder during pregnancy and the postpartum period. J Clin Psychiatry. 2012;73(11):1456–61. https://doi.org/10.4088/JCP.12m07856.

    Article  PubMed  Google Scholar 

  61. Sharma V, Xie B, Campbell MK, Penava D, Hampson E, Mazmanian D, et al. A prospective study of diagnostic conversion of major depressive disorder to bipolar disorder in pregnancy and postpartum. Bipolar Disord. 2014;16(1):16–21. https://doi.org/10.1111/bdi.12140.

    Article  PubMed  Google Scholar 

  62. Blackmore ER, Rubinow DR, O'Connor TG, Liu X, Tang W, Craddock N, et al. Reproductive outcomes and risk of subsequent illness in women diagnosed with postpartum psychosis. Bipolar Disord. 2013;15(4):394–404. https://doi.org/10.1111/bdi.12071.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sit D, Rothschild AJ, Wisner KL. A review of postpartum psychosis. J Women's Health (Larchmt). 2006;15(4):352–68. https://doi.org/10.1089/jwh.2006.15.352.

    Article  Google Scholar 

  64. Brockington IF, Oates M, Rose G. Prepartum psychosis. J Affect Disord. 1990;19(1):31–5. https://doi.org/10.1016/0165-0327(90)90006-T.

    Article  CAS  PubMed  Google Scholar 

  65. Diav-Citrin O, Shechtman S, Ornoy S, Arnon J, Schaefer C, Garbis H, et al. Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study. J Clin Psychiatry. 2005;66(3):317–22. https://doi.org/10.4088/JCP.v66n0307.

    Article  CAS  PubMed  Google Scholar 

  66. Leiknes KA, Cooke MJ, Jarosch-von Schweder L, Harboe I, Hoie B. Electroconvulsive therapy during pregnancy: a systematic review of case studies. Arch Womens Ment Health. 2015;18(1):1–39. https://doi.org/10.1007/s00737-013-0389-0.

    Article  PubMed  Google Scholar 

  67. Ennis ZN, Damkier P. Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review. Basic Clin Pharmacol Toxicol. 2015;116(4):315–20. https://doi.org/10.1111/bcpt.12372.

    Article  CAS  PubMed  Google Scholar 

  68. Coughlin CG, Blackwell KA, Bartley C, Hay M, Yonkers KA, Bloch MH. Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy. Obstet Gynecol. 2015;125(5):1224–35. https://doi.org/10.1097/AOG.0000000000000759.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Western University, London, Canada

    Michael Thomson

  2. Department of Psychiatry, Department of Obstetrics and Gynecology, Western University, London, Canada

    Verinder Sharma

  3. Parkwood Institute, 550 Wellington Road, London, ON, N6C 0A7, Canada

    Verinder Sharma

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Michael Thomson declares no conflict of interest.

Verinder Sharma reports grants from Assurex, Genome Canada, Neurocrine Biosciences, Sage Therapeutics, Stanley Medical Research Institute and Sunovion Pharmaceuticals outside the submitted work.

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

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This article is part of the Topical Collection on Bipolar Disorders

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Thomson, M., Sharma, V. Weighing the Risks: the Management of Bipolar Disorder During Pregnancy. Curr Psychiatry Rep 20, 20 (2018). https://doi.org/10.1007/s11920-018-0882-2

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