Changes in Lamotrigine Concentration During Pregnancy: Case Report

Introduction Determining the concentration of antiepileptic drugs is one of the most important factors in assessing the effectiveness of epilepsy treatment. Even small changes in drug concentration, around 20%, are associated with the frequency of seizures. Drug concentrations can fluctuate due to altered pharmacokinetics. Pregnancy is one such condition, as fluid balance and hormonal concentration in the body changes. Case Presentation A woman, aged 28, experienced an epileptic seizure in the 13th week of pregnancy. The patient has been diagnosed with epilepsy since the age of 14, and recently takes lamotrigine at 250 mg per day. The seizure-free period lasted 4,5 years. Serum lamotrigine concentration was measured at 4,29 mcg/ml, which had decreased compared to the result 3 months earlier. It was decided to increase the dosage to 300 mg per day. During pregnancy, 3 more epileptic seizures occurred. Testing revealed lamotrigine concentrations diminishing as low as 2,08 mcg/ml. The dosage was increased to 450 mg per day, which determined successful delivery. 2 months after delivery, the lamotrigine concentration was measured at 10,32 mcg/ml. It was decided to reduce the dosage to 400 mg per day. Subsequent testing showed a concentration of 8,75 mcg/ml, and a stable balance was achieved. Discussion Blood plasma volume increases throughout pregnancy, with the most significant changes occurring in the second trimester. In response to the increased blood volume, the glomerular filtration rate physiologically rises, potentially leading to increased excretion of substances, including drugs, in the urine. It is estimated that for many women (77%) taking lamotrigine, drug excretion increases by 220%. On the other hand, estradiol concentrations rise during pregnancy, which stimulates an increase in the UGT1A4 enzyme. This accelerates the metabolism of lamotrigine into an inactive metabolite. Conclusions Due to physiological changes in pregnancy, especially, during the second trimester, the concentration of lamotrigine decreased by more than 50%, resulting in the occurrence of epileptic seizures. After each seizure drug dosage was increased, which leads to safe delivery. Therefore, patients taking lamotrigine, particularly during pregnancy, must be closely monitored for potential insufficient concentrations, which could trigger epileptic seizures.