Lamotrigine concentrations fall by two-thirds by 32 weeks of pregnancy — and the fall differs by drug

Design

prospective multicentre observational cohort with linear mixed-effects models and model averaging

Population

947 women with epilepsy aged 18-45 in China, 1,638 samples (451 during pregnancy, 228 women); 64.3% on polytherapy

Primary outcome

concentration-to-dose ratio of antiseizure medications by gestational age

Effect

lamotrigine -28.8%, -54.3%, -63.2% by trimester (nadir -65.8% at 32 weeks); levetiracetam -26.2%, -40.1%, -31.0% (nadir -35.5% at 24 weeks); oxcarbazepine metabolite -23.1%, -32.6%, -44.3%; lacosamide -10.8% in the second trimester

A prospective multicentre Chinese cohort followed 947 women with epilepsy aged 18 to 45, contributing 1,638 steady-state trough samples between 2019 and 2025, of which 451 were taken during pregnancy. Concentration-to-dose ratio was the measure, which separates pharmacokinetic change from dose change.

The falls are drug-specific and large. Lamotrigine declined 28.8% in the first trimester, 54.3% in the second and 63.2% in the third, reaching a nadir of 65.8% at 32 weeks. Levetiracetam fell 26.2%, 40.1% and 31.0% by trimester, with its nadir of 35.5% at 24 weeks — note that it recovers somewhat in the third trimester while lamotrigine does not. The oxcarbazepine metabolite declined progressively to 44.3%. Lacosamide changed least, falling 10.8% in the second trimester only.

Those different trajectories are the practically useful part. A single 'check levels in pregnancy' instruction does not capture that lamotrigine needs watching right through to term while levetiracetam's worst point comes mid-pregnancy.

The authors' closing observation deserves weight: interindividual variability remained the dominant determinant of concentration, above gestational age, concomitant drugs or body weight. Population averages tell you when to look; they do not tell you what you will find.

• Obtain a preconception or early-pregnancy baseline concentration — later values are uninterpretable without one
• Monitor lamotrigine through to term; the nadir is around 32 weeks, not mid-pregnancy
• Check levetiracetam around the second trimester, when its fall is greatest
• Record body weight alongside the level; higher weight was associated with lower concentration-to-dose ratios for most drugs
• Plan the postpartum dose reduction at the same visit as the antenatal increase, so it is not forgotten

The statistics, in plain English

Concentration-to-dose ratio is used rather than raw concentration because it removes the effect of dose changes made during the pregnancy — a falling C/D ratio means the body is clearing more drug per milligram given, which is the thing to correct for. The declines are reported with tight confidence intervals and p-values below 0.001 for lamotrigine, levetiracetam and oxcarbazepine, so the average trajectories are well established. Lacosamide's fall, 10.8% with p = 0.035 in the second trimester only, is a much weaker finding that could reflect a smaller sample. The authors' point that interindividual variability dominated all measured covariates means these percentages predict the group, not the patient in front of you.

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