Table 2 Foetal and maternal risks associated with selected mood stabilisers. Compiled from various sources [50, 53, 78, 79, 101,102,103,104,105,106]
Medication | Risks to offspring associated with use in pregnancy | Maternal risks associated with use in pregnancy |
|---|---|---|
Lithium | Severe toxicity in newborn. There are limited and conflicting data regarding the risk of cardiovascular malformations (including Ebstein’s anomaly) following lithium exposure in utero. A large cohort study in 2017 showed that the relative risk was still elevated (1.7), and also dose dependent, but lower than previously thought. Absolute risk remains low (< 1/1500). Non-teratogenic associations include low birth weight, cyanosis, bradycardia, GI bleeding, polyhydramnios, seizures. | Renal lithium clearance rises during pregnancy, so levels need to be monitored regularly to maintain therapeutic levels. |
Valproate | Significantly elevates the risk of major defects (7 times higher). These include spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyly and craniosynostosis. See Table 4 and main text for further details. Non-teratogenic associations include case reports of intra-uterine growth restriction, infant hepatic toxicity and foetal distress during labour. Neurodevelopmental associations – foetal exposure to valproate in utero is associated with 1.7 times risk of autism spectrum disorder. | Increased hepatic clearance of valproate and increased apparent volume of distribution cause lower maternal levels of the drug. |
Carbamazepine | Risk of major congenital abnormalities increased 1.8 times, including malformations of neural tube, urinary tract and cardiovascular system, and cleft palate. | Crosses placenta and lowers maternal serum levels, so doses may need to be increased. |
Lamotrigine | Conflicting evidence on the risk of malformations, especially regarding dose response. Evidence emerging that it appears to be a relatively safe drug in pregnancy. | Crosses placenta and lowers maternal serum levels, so dose may need to be increased. Dizziness, diplopia and ataxia have been reported following these dose increases in pregnant women. |
Atypical antipsychotics | Most do not appear to significantly increase malformation rate. Risperidone requires additional study. | Crosses placenta and lowers maternal serum levels, so doses may need to be increased. |