Pregnancy reduces the effects of a commonly used drug to treat bipolar disorder, making women with the condition who are pregnant vulnerable to recurring episodes, according to the findings of one of the first in-depth studies of how physiological changes during pregnancy can reduce a drug’s effectiveness. The new findings will help psychiatrists and physicians prevent bipolar manic and depressive symptoms during pregnancy, which are risky for the health of the mother and her unborn child.
When a woman with bipolar disorder becomes pregnant, she and her physician often don't realize her medication needs adjusting to prevent symptom recurrence, which is more likely during pregnancy. There also is little information and research to guide dosing for psychiatric medications during pregnancy.
Approximately 4.4 million women in the United States have bipolar disorder, with women of childbearing age having the highest prevalence.
All study participants took lamotrigine, a commonly used drug, throughout their pregnancy. Lamotrigine serum samples were obtained from 8 mother-infant pairs at different time points during pregnancy and the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg.
The new study shows that blood concentrations of lamotrigine decreased in pregnant women. In about half of the women in the study, depressive symptoms worsened as blood levels of lamotrigine dropped. The drug levels fell because women have increased metabolism during pregnancy.
Compared with the baseline blood level of lamotrigine during pregnancy, the level-to-dose ratios obtained within 4 weeks after delivery increased an average of 402%. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks, the researchers stated. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels.
"Now physicians change the dose of the drug in response to women's symptoms worsening," said lead investigator Crystal Clark, M.D., an assistant professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and a psychiatrist at Northwestern Memorial Hospital. "We need to optimize their medication dosing so they stay well."
The study results will help physicians understand how to increase their patients' doses during pregnancy and then reduce them postpartum to avoid toxicity, Clark said.
Depressive episodes, as opposed to manic, are most likely to recur in pregnant women with bipolar disorder.
"The safety of the fetus is at risk," Clark said. "Pregnant women that are depressed are less likely to take care of themselves which often leads to poor nutrition, lack of compliance with prenatal care and isolation from family and friends. It has also been linked to premature births and babies with low birth weights among other poor birth outcomes."
- Increased metabolism during pregnancy causes serum-level:dose ratios of lamotrigine to be lower during pregnancy than in the postpartum period.
- The blood concentration of lamotrigine after delivery can be up to 4 times higher than that during pregnancy.
- Doses of lamotrigine should be increased during pregnancy and then decreased after delivery to avoid toxicity.
Clark CT, Klein AM, Perel JM, et al. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry. 2013;170:1240-1247. doi: 10.1176/appi.ajp.2013.13010006.