“Neurologists who treat pregnant epilepsy patients know that lamotrigine levels go down and have developed algorithms to guide dosing during pregnancy and also postpartum, but there are no algorithms for psychiatrists treating pregnant bipolar patients,” Crystal T. Clark, MD, from Northwestern University Feinberg School of Medicine, Chicago, told Medscape Medical News.
“Lamotrigine levels drop significantly in concentration across pregnancy, to the point where you would not expect them to be therapeutic, and yet many people do not even realize this because they are not reading the neurology literature. I would like to increase awareness of this and encourage the development of a lamotrigine dosing algorithm,” she said.
Dr. Clark presented data on serial serum levels of lamotrigine in pregnant patients with bipolar disorder here at the American Society of Clinical Psychopharmacology (ASCP) 2014 Annual Meeting.
She also compared postpartum lamotrigine serum levels as well as levels of lamotrigine in the umbilical cord and in infants exposed to lamotrigine through breast milk.
The serum samples were obtained from 8 mother-infant pairs at different time points during pregnancy and postpartum.
The women were taking lamotrigine at doses that ranged from 100 mg to 300 mg, once daily; 3 women had an increase of 50 mg of their daily dose as their pregnancy progressed.
Serum level-to-dose ratios were lower in pregnancy than postpartum. In 2 patients, these ratios reached the lowest serum level in the 3rd trimester.
Level-to-dose ratios obtained in the first 4 weeks of the postpartum period were 402% greater (mean) compared with levels at the start of pregnancy.Dr. Clark found that the change in lamotrigine concentrations fluctuated widely in the postpartum period, ranging from a 30% decrease to a 640% increase, compared with the first level obtained in pregnancy.
Compared with levels in the 3rd trimester, when they were lowest, lamotrigine serum concentration levels increased an average of 154% in the first 5 weeks postpartum.
The most dramatic increase in lamotrigine serum levels occurred at 1.5 weeks’ postpartum.
At delivery, the mean infant cord level was 66% of the mother’s serum level, and the mean breast-fed infant serum level was 32.5% of the mother’s serum level.
“I hope my study highlights these changes to educate my colleagues, and also prompts us to see how we might develop an algorithm for women with bipolar disorder to keep them from having worsening symptoms and also to keep wellness for the mother postpartum, because as we see, if you’re increasing the dose during pregnancy, you’ve got to decrease the dose postpartum and keep women from becoming toxic,” Dr. Clark said.
Commenting on the study for Medscape Medical News, Lee S. Cohen, MD, director, Center for Women’s Mental Health at Massachusetts General Hospital, Boston, and professor of psychiatry at Harvard Medical School, said the findings are “interesting but not particularly surprising.”
Careful monitoring is critical for these women, Dr. Cohen added.”We have known for many years that the concentrations of medications like lamotrigine decrease during pregnancy, but it is nice to see that quantified, as it is in this report.” However, Dr. Cohen cautioned, arbitrarily raising the dose of lamotrigine during pregnancy would not be appropriate, “unless there are clinical signs of worsening.”
“Bipolar women are at very high risk for postpartum depression, on the order of 5 times what we see in the general population, so it is very important for those who are on lamotrigine to have careful guidance from their doctors to hopefully minimize the risk for postpartum depression during such a critical time,” he said.
The study was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Clark reported no relevant financial relationships. Dr. Cohen reported financial relationships with AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Cephalon Inc, GlaxoSmithKline, National Institute of Mental Health, National Institute on Aging, Noven Pharmaceuticals, Ortho-McNeil Janssen, PamLab LLC, and Sunovion Pharmaceuticals Inc.
American Society of Clinical Psychopharmacology (ASCP) 2014 Annual Meeting. Abstract 78. Presented June 16, 2014.