A Review of Mood-Stabilizing Medications in Pregnancy: Risks, Benefits, and Recommendations

Bipolar disorder is a chronic condition that requires long-term management, often with mood-stabilizing medications. However, the use of these medications during pregnancy presents a challenge due to the potential risks to the developing fetus.

One such medication, sodium valproate, is associated with a significantly higher risk of neural tube defects (NTDs) and other developmental issues. The baseline risk of NTDs in the general population is approximately 1 in 1000 (0.1%). However, the use of valproate during pregnancy increases this risk significantly, with studies showing that approximately 1 to 2 in 100 babies (1%-2%) born to women taking valproate in pregnancy will have an NTD (Tomson et al., 2018).

Women with bipolar disorder who wish to become pregnant often need to consider alternative medications. Two often-considered alternatives are lamotrigine and lithium.

Lamotrigine (Lamictal)

Lamotrigine has been increasingly used during pregnancy due to its lower teratogenic risk profile compared to other mood stabilizers. However, some studies suggest a small increased risk of oral clefts with lamotrigine exposure in utero. A meta-analysis by Meador et al. (2018) indicated a prevalence rate of oral clefts of 0.27% (27 per 10,000) with lamotrigine use in the first trimester, which is slightly higher than the baseline risk in the general population (about 10 per 10,000).

Despite this small increase, lamotrigine is often considered one of the safer mood-stabilizing drugs for use during pregnancy due to the overall lower risk of major congenital malformations (Meador et al., 2018).

Lithium

Lithium, a first-line treatment for bipolar disorder, is also an option during pregnancy. However, it has been associated with an increased risk of cardiac malformations, specifically Ebstein’s anomaly, a rare heart defect. The baseline risk of Ebstein’s anomaly in the general population is approximately 1 in 20,000 (0.005%) (Medsafe, 2018). Research indicates that lithium exposure during the first trimester may increase this risk to around 1 in 1,000 to 2,000 (0.05%-0.1%) (Medsafe, 2018; Patorno et al., 2017).

While this represents a significant relative increase, the absolute risk remains small. The benefits of lithium, particularly for individuals with a history of severe manic episodes, often outweigh the potential risks.

Antipsychotics

Atypical antipsychotics such as olanzapine, quetiapine, or lurasidone are also considered for use during pregnancy, though their safety profiles are not as well established as those of lamotrigine and lithium (Gentile, 2017).

Efficacy in Treating and Preventing Mania/Hypomania

In addition to the safety profiles of mood stabilizers during pregnancy, it’s also important to consider the efficacy of these medications in managing bipolar disorder and preventing relapses of mania or hypomania.

Sodium Valproate: Valproate is a highly effective mood stabilizer, and it’s particularly potent in treating and preventing manic episodes. However, as previously discussed, its use during pregnancy is associated with significant risks to the fetus, leading many clinicians to avoid its use in women of childbearing age when other effective alternatives are available.

Lamotrigine: Lamotrigine is considered effective in managing bipolar disorder, particularly in the prevention of depressive episodes. Its efficacy in preventing manic episodes is considered less robust than that of lithium or valproate, but it can still be effective, especially in combination with other treatments.

Lithium: Lithium is a first-line treatment for bipolar disorder, and it’s particularly effective at preventing manic relapses. Its use during pregnancy is associated with a small increased risk of cardiac malformations, but for many women, the benefits in terms of mood stabilization may outweigh the risks.

Atypical Antipsychotics: Several atypical antipsychotics, including olanzapine, quetiapine, and lurasidone, have been shown to be effective in treating acute mania and in maintenance treatment to prevent relapse. Their safety profiles during pregnancy are not as well established as those of lamotrigine and lithium, but they can be considered when other treatments are not suitable or effective.

Conclusion

Changing medications should always be done under the close supervision of a psychiatrist, and the patient should be stable on the new medication before attempting to conceive. Additionally, it’s crucial to involve an obstetrician who specializes in high-risk pregnancies. Folic acid supplementation is recommended for all women of childbearing age, but particularly for those on antiepileptic drugs, to reduce the risk of neural tube defects.

While these are general recommendations, each patient’s case is unique and should be managed individually, considering their unique medical history and circumstances.

References

Gentile, S. (2017). Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophrenia bulletin, 43(4), 752-761.

Meador, K. J., Baker, G. A., Browning, N., Clayton-Smith, J., Combs-Cantrell, D. T., Cohen, M., … & Kalayjian, L. A. (2018). Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. The Lancet Neurology, 12(3), 244-252.

Tomson, T., Battino, D., Bonizzoni, E., Craig, J., Lindhout, D., Sabers, A., … & EURAP study group. (2018). Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. The Lancet Neurology, 17(6), 530-540.

Medsafe. (2018). Prescriber Update 39(4): 50-56. Retrieved from: https://www.medsafe.govt.nz/profs/PUArticles/December2018/MedicinesUseInPregnancy.htm

Patorno, E., Huybrechts, K. F., Bateman, B. T., Cohen, J. M., Desai, R. J., Mogun, H., … & Hernandez-Diaz, S. (2017). Lithium use in pregnancy and the risk of cardiac malformations. The New England journal of medicine, 376(23), 2245-2254.

Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., … & Sharma, V. (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.

National Collaborating Centre for Mental Health (UK). (2014). Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care. Leicester (UK): British Psychological Society.