PHARMACOLOGICAL STRATEGIES FOR THE TREATMENT OF BIPOLAR DISORDER IN PREGNANT WOMEN: A SYSTEMATIC REVIEW

Keywords: Bipolar Disorder, Treatment of Bipolar Disorder During Pregnancy, Mood Stabilizers, Psychofarmakology

Abstract

Introduction: Bipolar affective disorder (BAD) is a chronic mental disorder characterized by recurrent episodes of mania or hypomania and depression, with periods of remission in between. In women of reproductive age, BAD is associated with an increased risk of early pregnancy, perinatal complications, and postpartum relapse. The cornerstone of treatment is pharmacotherapy, including mood stabilizers as well as antipsychotic and antidepressant drugs. Pharmacological treatment during pregnancy reduces the risk of relapse but carries a potential risk of developmental defects and obstetric complications. Optimal therapeutic management requires individualized treatment.

Aim of the study: The aim of this work was to review the available literature on the pharmacological treatment of bipolar affective disorder (BAD) in pregnant women and to summarize the current state of knowledge. The safety profile of the drugs used and their effects on the mother and fetus during BAD pharmacotherapy are presented.

Methods and materials: A review of the literature available in the PubMed database was conducted using the following keywords: „treatment of bipolar disorder during pregnancy”, „teratogenicity”, „mood stabilizers”, „lithium”, „antidepressants”, „antipsychotic agents”, „congenital malformations”, „bipolar depression”, „valproate”, „lamotrigine”, „carbamazepine”, „postpartum relapse” and „anticonvulsants”.

Conclusion: Treatment of bipolar affective disorder in women of reproductive age is a significant clinical challenge. Continuation of pharmacotherapy during pregnancy is crucial for mood stabilization and prevention of postpartum episodes. Drug selection should be based on a risk–benefit assessment. Individualized pharmacotherapy and regular monitoring of mother and fetus are essential for optimal treatment outcomes and safety of both mother and child.

References

Newport, D. J., Calamaras, M. R., DeVane, C. L., Donovan, J., Beach, A. J., Winn, S., Knight, B. T., Gibson, B. B., Viguera, A. C., Owens, M. J., Nemeroff, C. B., & Stowe, Z. N. (2007). Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. The American journal of psychiatry, 164(8), 1214–1220. https://doi.org/10.1176/appi.ajp.2007.06111886

Viguera, A. C., Whitfield, T., Baldessarini, R. J., Newport, D. J., Stowe, Z., Reminick, A., Zurick, A., & Cohen, L. S. (2007). Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. The American journal of psychiatry, 164(12), 1817–1923. https://doi.org/10.1176/appi.ajp.2007.06101639

Bodén, R., Lundgren, M., Brandt, L., Reutfors, J., Andersen, M., & Kieler, H. (2012). Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ (Clinical research ed.), 345, e7085. https://doi.org/10.1136/bmj.e7085

Merikangas, K. R., Jin, R., He, J. P., Kessler, R. C., Lee, S., Sampson, N. A., Viana, M. C., Andrade, L. H., Hu, C., Karam, E. G., Ladea, M., Medina-Mora, M. E., Ono, Y., Posada-Villa, J., Sagar, R., Wells, J. E., & Zarkov, Z. (2011). Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of general psychiatry, 68(3), 241–251. https://doi.org/10.1001/archgenpsychiatry.2011.12

Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., Alda, M., MacQueen, G., Milev, R. V., Ravindran, A., O'Donovan, C., McIntosh, D., Lam, R. W., Vazquez, G., Kapczinski, F., McIntyre, R. S., … Berk, M. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar disorders, 20(2), 97–170. https://doi.org/10.1111/bdi.12609

Stevens, A. W. M. M., Goossens, P. J. J., Knoppert-van der Klein, E. A. M., Draisma, S., Honig, A., & Kupka, R. W. (2019). Risk of recurrence of mood disorders during pregnancy and the impact of medication: A systematic review. Journal of affective disorders, 249, 96–103. https://doi.org/10.1016/j.jad.2019.02.018

Fornaro, M., Maritan, E., Ferranti, R., Zaninotto, L., Miola, A., Anastasia, A., Murru, A., Solé, E., Stubbs, B., Carvalho, A. F., Serretti, A., Vieta, E., Fusar-Poli, P., McGuire, P., Young, A. H., Dazzan, P., Vigod, S. N., Correll, C. U., & Solmi, M. (2020). Lithium Exposure During Pregnancy and the Postpartum Period: A Systematic Review and Meta-Analysis of Safety and Efficacy Outcomes. The American journal of psychiatry, 177(1), 76–92. https://doi.org/10.1176/appi.ajp.2019.19030228

Patorno, E., Huybrechts, K. F., Bateman, B. T., Cohen, J. M., Desai, R. J., Mogun, H., Cohen, L. S., & Hernandez-Diaz, S. (2017). Lithium Use in Pregnancy and the Risk of Cardiac Malformations. The New England journal of medicine, 376(23), 2245–2254. https://doi.org/10.1056/NEJMoa1612222

Nierenberg, A. A., Agustini, B., Köhler-Forsberg, O., Cusin, C., Katz, D., Sylvia, L. G., Peters, A., & Berk, M. (2023). Diagnosis and Treatment of Bipolar Disorder: A Review. JAMA, 330(14), 1370–1380. https://doi.org/10.1001/jama.2023.18588

Wesseloo, R., Kamperman, A. M., Munk-Olsen, T., Pop, V. J., Kushner, S. A., & Bergink, V. (2016). Risk of Postpartum Relapse in Bipolar Disorder and Postpartum Psychosis: A Systematic Review and Meta-Analysis. The American journal of psychiatry, 173(2), 117–127. https://doi.org/10.1176/appi.ajp.2015.15010124

Poels, E. M. P., Schrijver, L., White, T. J. H., Roza, S. J., Zarchev, M. G., Bijma, H., Honig, A., van Kamp, I. L., Hoogendijk, W. J. G., Kamperman, A. M., & Bergink, V. (2022). The effect of prenatal lithium exposure on the neuropsychological development of the child. Bipolar disorders, 24(3), 310–319. https://doi.org/10.1111/bdi.13133

Weston, J., Bromley, R., Jackson, C. F., Adab, N., Clayton-Smith, J., Greenhalgh, J., Hounsome, J., McKay, A. J., Tudur Smith, C., & Marson, A. G. (2016). Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. The Cochrane database of systematic reviews, 11(11), CD010224. https://doi.org/10.1002/14651858.CD010224.pub2

Ornoy A. (2009). Valproic acid in pregnancy: how much are we endangering the embryo and fetus?. Reproductive toxicology (Elmsford, N.Y.), 28(1), 1–10. https://doi.org/10.1016/j.reprotox.2009.02.014

Tanoshima, M., Kobayashi, T., Tanoshima, R., Beyene, J., Koren, G., & Ito, S. (2015). Risks of congenital malformations in offspring exposed to valproic acid in utero: A systematic review and cumulative meta-analysis. Clinical pharmacology and therapeutics, 98(4), 417–441. https://doi.org/10.1002/cpt.158

Vieta, E., Ghorpade, S., Biswas, A., Sarkar, A., Phansalkar, A., & Cooper, J. (2024). Lamotrigine efficacy, safety, and tolerability for women of childbearing age with bipolar I disorder: Meta-analysis from four randomized, placebo-controlled maintenance studies. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 78, 81–92. https://doi.org/10.1016/j.euroneuro.2023.09.001

Cunnington, M. C., Weil, J. G., Messenheimer, J. A., Ferber, S., Yerby, M., & Tennis, P. (2011). Final results from 18 years of the International Lamotrigine Pregnancy Registry. Neurology, 76(21), 1817–1823. https://doi.org/10.1212/WNL.0b013e31821ccd18

Petersen, I., Collings, S. L., McCrea, R. L., Nazareth, I., Osborn, D. P., Cowen, P. J., & Sammon, C. J. (2017). Antiepileptic drugs prescribed in pregnancy and prevalence of major congenital malformations: comparative prevalence studies. Clinical epidemiology, 9, 95–103. https://doi.org/10.2147/CLEP.S118336

Tomson, T., Battino, D., Bonizzoni, E., Craig, J., Lindhout, D., Perucca, E., Sabers, A., Thomas, S. V., Vajda, F., & EURAP Study Group (2018). Comparative risk of major congenital malformations with eight different antiepileptic drugs: a prospective cohort study of the EURAP registry. The Lancet. Neurology, 17(6), 530–538. https://doi.org/10.1016/S1474-4422(18)30107-8

Coughlin, C. G., Blackwell, K. A., Bartley, C., Hay, M., Yonkers, K. A., & Bloch, M. H. (2015). Obstetric and neonatal outcomes after antipsychotic medication exposure in pregnancy. Obstetrics and gynecology, 125(5), 1224–1235. https://doi.org/10.1097/AOG.0000000000000759

Giménez, A., Pacchiarotti, I., Gil, J., Murru, A., Gomes, S. P., Pinzón, J. E., Anmella, G., Gómez-Ramiro, M., Verdolini, N., Valentí, M., Goikolea, J. M., & Vieta, E. (2019). Adverse outcomes during pregnancy and major congenital malformations in infants of patients with bipolar and schizoaffective disorders treated with antiepileptic drugs: A systematic review. Działania niepożądane w czasie ciąży i poważne wrodzone wady rozwojowe u niemowląt pacjentek z zaburzeniami afektywnymi dwubiegunowymi i zaburzeniami schizoafektywnymi leczonych lekami przeciwpadaczkowymi: przegląd systematyczny. Psychiatria polska, 53(2), 223–244. https://doi.org/10.12740/PP/105906

Huybrechts, K. F., Hernández-Díaz, S., Patorno, E., Desai, R. J., Mogun, H., Dejene, S. Z., Cohen, J. M., Panchaud, A., Cohen, L., & Bateman, B. T. (2016). Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA psychiatry, 73(9), 938–946. https://doi.org/10.1001/jamapsychiatry.2016.1520

Merikangas, K. R., Jin, R., He, J. P., Kessler, R. C., Lee, S., Sampson, N. A., Viana, M. C., Andrade, L. H., Hu, C., Karam, E. G., Ladea, M., Medina-Mora, M. E., Ono, Y., Posada-Villa, J., Sagar, R., Wells, J. E., & Zarkov, Z. (2011). Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of general psychiatry, 68(3), 241–251. https://doi.org/10.1001/archgenpsychiatry.2011.12

Yang, H. S., Hsu, J. W., Huang, K. L., Tsai, S. J., Bai, Y. M., Su, T. P., Chen, T. J., & Chen, M. H. (2023). Risk of teenage pregnancy among adolescents with bipolar disorder: a cohort study of 35,398 adolescent girls. European child & adolescent psychiatry, 32(10), 2001–2008. https://doi.org/10.1007/s00787-022-02029-z

Gilden, J., Poels, E. M. P., Lambrichts, S., Vreeker, A., Boks, M. P. M., Ophoff, R. A., Kahn, R. S., Kamperman, A. M., & Bergink, V. (2021). Bipolar episodes after reproductive events in women with bipolar I disorder, A study of 919 pregnancies. Journal of affective disorders, 295, 72–79. https://doi.org/10.1016/j.jad.2021.08.006

Zarate, C. A., Jr, Tohen, M., Land, M., & Cavanagh, S. (2000). Functional impairment and cognition in bipolar disorder. The Psychiatric quarterly, 71(4), 309–329. https://doi.org/10.1023/a:1004632206684

Manji, H. K., Henter, I. D., & Zarate, C. A., Jr (2011). Bipolar disorder: a neurobiological synthesis. Current topics in behavioral neurosciences, 5, 331–340. https://doi.org/10.1007/7854_2010_98

Uguz, F., Sharma, V., Boyce, P., Clark, C. T., Galbally, M., Koukopoulos, A., Marsh, W., Stevens, A., & Viguera, A. (2023). Prophylactic Management of Women With Bipolar Disorder During Pregnancy and the Perinatal Period: Clinical Scenario-Based Practical Recommendations From A Group of Perinatal Psychiatry Authors. Journal of clinical psychopharmacology, 43(5), 434–452. https://doi.org/10.1097/JCP.0000000000001740

Tondo, L., Alda, M., Bauer, M., Bergink, V., Grof, P., Hajek, T., Lewitka, U., Licht, R. W., Manchia, M., Müller-Oerlinghausen, B., Nielsen, R. E., Selo, M., Simhandl, C., Baldessarini, R. J., & International Group for Studies of Lithium (IGSLi) (2019). Clinical use of lithium salts: guide for users and prescribers. International journal of bipolar disorders, 7(1), 16. https://doi.org/10.1186/s40345-019-0151-2

Broeks, S. C., Thisted Horsdal, H., Glejsted Ingstrup, K., & Gasse, C. (2017). Psychopharmacological drug utilization patterns in pregnant women with bipolar disorder - A nationwide register-based study. Journal of affective disorders, 210, 158–165. https://doi.org/10.1016/j.jad.2016.12.001

Wesseloo, R., Liu, X., Clark, C. T., Kushner, S. A., Munk-Olsen, T., & Bergink, V. (2017). Risk of postpartum episodes in women with bipolar disorder after lamotrigine or lithium use during pregnancy: A population-based cohort study. Journal of affective disorders, 218, 394–397. https://doi.org/10.1016/j.jad.2017.04.070

Frayne, J., Nguyen, T., Mok, T., Hauck, Y., & Liira, H. (2018). Lithium exposure during pregnancy: outcomes for women who attended a specialist antenatal clinic. Journal of psychosomatic obstetrics and gynaecology, 39(3), 211–219. https://doi.org/10.1080/0167482X.2017.1337743

Munk-Olsen, T., Liu, X., Viktorin, A., Brown, H. K., Di Florio, A., D'Onofrio, B. M., Gomes, T., Howard, L. M., Khalifeh, H., Krohn, H., Larsson, H., Lichtenstein, P., Taylor, C. L., Van Kamp, I., Wesseloo, R., Meltzer-Brody, S., Vigod, S. N., & Bergink, V. (2018). Maternal and infant outcomes associated with lithium use in pregnancy: an international collaborative meta-analysis of six cohort studies. The lancet. Psychiatry, 5(8), 644–652. https://doi.org/10.1016/S2215-0366(18)30180-9

Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W., & NEAD Study Group (2013). Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. The Lancet. Neurology, 12(3), 244–252. https://doi.org/10.1016/S1474-4422(12)70323-X

Tomson, T., & Battino, D. (2012). Teratogenic effects of antiepileptic drugs. The Lancet. Neurology, 11(9), 803–813. https://doi.org/10.1016/S1474-4422(12)70103-5

Tomson, T., Battino, D., Bonizzoni, E., Craig, J., Lindhout, D., Sabers, A., Perucca, E., Vajda, F., & EURAP study group (2011). Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. The Lancet. Neurology, 10(7), 609–617. https://doi.org/10.1016/S1474-4422(11)70107-7

Huybrechts, K. F., Straub, L., Karlsson, P., Pazzagli, L., Furu, K., Gissler, M., Hernandez-Diaz, S., Nørgaard, M., Zoega, H., Bateman, B. T., Cesta, C. E., Cohen, J. M., Leinonen, M. K., Reutfors, J., Selmer, R. M., Suarez, E. A., Ulrichsen, S. P., & Kieler, H. (2023). Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US. JAMA psychiatry, 80(2), 156–166. https://doi.org/10.1001/jamapsychiatry.2022.4109

Wang, Z., Chan, A. Y. L., Coghill, D., Ip, P., Lau, W. C. Y., Simonoff, E., Brauer, R., Wei, L., Wong, I. C. K., & Man, K. K. C. (2021). Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age. JAMA internal medicine, 181(10), 1332–1340. https://doi.org/10.1001/jamainternmed.2021.4571

Straub, L., Hernández-Díaz, S., Bateman, B. T., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B., McDougle, C. J., Suarez, E. A., Zhu, Y., Zakoul, H., Mogun, H., & Huybrechts, K. F. (2022). Association of Antipsychotic Drug Exposure in Pregnancy With Risk of Neurodevelopmental Disorders: A National Birth Cohort Study. JAMA internal medicine, 182(5), 522–533. https://doi.org/10.1001/jamainternmed.2022.0375

Huang, H., Coleman, S., Bridge, J. A., Yonkers, K., & Katon, W. (2014). A meta-analysis of the relationship between antidepressant use in pregnancy and the risk of preterm birth and low birth weight. General hospital psychiatry, 36(1), 13–18. https://doi.org/10.1016/j.genhosppsych.2013.08.002

Ross, L. E., Grigoriadis, S., Mamisashvili, L., Vonderporten, E. H., Roerecke, M., Rehm, J., Dennis, C. L., Koren, G., Steiner, M., Mousmanis, P., & Cheung, A. (2013). Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA psychiatry, 70(4), 436–443. https://doi.org/10.1001/jamapsychiatry.2013.684

Eke, A. C., Saccone, G., & Berghella, V. (2016). Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG : an international journal of obstetrics and gynaecology, 123(12), 1900–1907. https://doi.org/10.1111/1471-0528.14144

Kobayashi, T., Matsuyama, T., Takeuchi, M., & Ito, S. (2016). Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reproductive toxicology (Elmsford, N.Y.), 65, 170–178. https://doi.org/10.1016/j.reprotox.2016.07.016

Kaplan, Y. C., Keskin-Arslan, E., Acar, S., & Sozmen, K. (2016). Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis. Reproductive toxicology (Elmsford, N.Y.), 66, 31–43. https://doi.org/10.1016/j.reprotox.2016.09.013

Kaplan, Y. C., Keskin-Arslan, E., Acar, S., & Sozmen, K. (2017). Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta-analysis of cohort studies. British journal of clinical pharmacology, 83(12), 2798–2806. https://doi.org/10.1111/bcp.13382

Andalib, S., Emamhadi, M. R., Yousefzadeh-Chabok, S., Shakouri, S. K., Høilund-Carlsen, P. F., Vafaee, M. S., & Michel, T. M. (2017). Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review. European psychiatry : the journal of the Association of European Psychiatrists, 45, 161–166. https://doi.org/10.1016/j.eurpsy.2017.06.001

Masarwa, R., Bar-Oz, B., Gorelik, E., Reif, S., Perlman, A., & Matok, I. (2019). Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis. American journal of obstetrics and gynecology, 220(1), 57.e1–57.e13. https://doi.org/10.1016/j.ajog.2018.08.030

De Vries, C., Gadzhanova, S., Sykes, M. J., Ward, M., & Roughead, E. (2021). A Systematic Review and Meta-Analysis Considering the Risk for Congenital Heart Defects of Antidepressant Classes and Individual Antidepressants. Drug safety, 44(3), 291–312. https://doi.org/10.1007/s40264-020-01027-x

Grove, K., Lewis, A. J., & Galbally, M. (2018). Prenatal Antidepressant Exposure and Child Motor Development: A Meta-analysis. Pediatrics, 142(1), e20180356. https://doi.org/10.1542/peds.2018-0356

Nulman, I., Rovet, J., Stewart, D. E., Wolpin, J., Gardner, H. A., Theis, J. G., Kulin, N., & Koren, G. (1997). Neurodevelopment of children exposed in utero to antidepressant drugs. The New England journal of medicine, 336(4), 258–262. https://doi.org/10.1056/NEJM199701233360404

Matalon, S., Schechtman, S., Goldzweig, G., & Ornoy, A. (2002). The teratogenic effect of carbamazepine: a meta-analysis of 1255 exposures. Reproductive toxicology (Elmsford, N.Y.), 16(1), 9–17. https://doi.org/10.1016/s0890-6238(01)00199-x

Jentink, J., Dolk, H., Loane, M. A., Morris, J. K., Wellesley, D., Garne, E., de Jong-van den Berg, L., & EUROCAT Antiepileptic Study Working Group (2010). Intrauterine exposure to carbamazepine and specific congenital malformations: systematic review and case-control study. BMJ (Clinical research ed.), 341, c6581. https://doi.org/10.1136/bmj.c6581

Wang, Z., Wong, I. C. K., Man, K. K. C., Alfageh, B. H., Mongkhon, P., & Brauer, R. (2021). The use of antipsychotic agents during pregnancy and the risk of gestational diabetes mellitus: a systematic review and meta-analysis. Psychological medicine, 51(6), 1028–1037. https://doi.org/10.1017/S003329171900401X

Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., Mogun, H., Levin, R., Kowal, M., Setoguchi, S., & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. The New England journal of medicine, 370(25), 2397–2407. https://doi.org/10.1056/NEJMoa1312828

Uguz F. (2020). Selective serotonin reuptake inhibitors and the risk of congenital anomalies: a systematic review of current meta-analyses. Expert opinion on drug safety, 19(12), 1595–1604. https://doi.org/10.1080/14740338.2020.1832080

Published
2026-02-16
Citations
How to Cite
Paweł Grzesikowski, & Paulina Klich. (2026). PHARMACOLOGICAL STRATEGIES FOR THE TREATMENT OF BIPOLAR DISORDER IN PREGNANT WOMEN: A SYSTEMATIC REVIEW. International Journal of Innovative Technologies in Social Science, (1(49). https://doi.org/10.31435/ijitss.1(49).2026.4978

Most read articles by the same author(s)