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Pregnant Women on Lamotrigine Have Greater Risk of Seizures When Drug Levels are Low: Presented at AES

By Paula Moyer

SAN DIEGO, CA -- December 7, 2006 -- Women with epilepsy who are treated with lamotrigine (Lamictal) during pregnancy and have low therapeutic levels of the drug have more frequent seizures, according to research presented here at the annual meeting of the 1^st North American Regional Epilepsy Congress (NAREC).

The meeting is organized by the American Epilepsy Society (AES) is joining with the Canadian League Against Epilepsy.

"Our analysis demonstrates that seizure worsening during pregnancy is associated with a low ratio-to-target concentration [of lamotrigine]," reported Page B. Pennell, MD, associate professor of neurology at Emory University School of Medicine in Atlanta, Georgia. "However, improved results are possible with an active therapeutic drug monitoring approach."

The dilemma is that both seizures and anticonvulsants are associated with fetal risks. However, because lamotrigine is associated with relatively low rates of malformations, physicians are prescribing it more often to women with epilepsy who are in their reproductive years. However, as with many medications, lamotrigine clearance has been reported to increase during pregnancy, resulting in low blood concentrations of the drug and, therefore, more frequent seizures. In fact, such exacerbations have been reported in 45% to 75% of women on lamotrigine monotherapy, according to the investigators.

Dr. Pennell and colleagues conducted a subset analysis of 30 women on lamotrigine monotherapy during pregnancy for whom they had adequate baseline information about seizure frequency and preconception target lamotrigine concentrations. The investigators then used the concentration data for therapeutic drug monitoring and made dosage adjustment recommendations according to the patient's seizure types and type of epilepsy syndrome, as well as seizure frequency, history of lamotrigine-related adverse effects, the fetus's gestational age, and what was considered to be the individual's target concentration of lamotrigine.

For each trimester of pregnancy, the investigators coded the relative frequency of all types of seizures in the following manner: 1 if the frequency of seizures was greater than baseline, 0 if the frequency was the same or less than baseline. For each trimester, they calculated the ratio-to-target concentration as the ratio of the current lamotrigine concentration compared with the baseline lamotrigine concentration.

The investigators documented a worsening of seizures during pregnancy in 28% of patients. Convulsive seizures, which are more hazardous to fetuses, worsened in 10% of patients. In the second and third trimesters, lamotrigene concentration ratios for patients with worsened seizures were significantly lower than ratios among those with stable seizures (P < .001 and P = .05, respectively). However, those associations were not seen in the first trimester.

The findings showed the need for research that could help clinicians define a treatment plan and dosing paradigm for lamotrigine use during pregnancy that would be adaptable to individual patients, Dr. Pennell said during her presentation on December 3^rd.

The study was funded by a grant from the National Institutes of Health Specialized Center of Research.


[Presentation title: Seizure Frequency in Women on Lamotrigine During Pregnancy Using Therapeutic Drug Monitoring. Abstract 2.146]

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