Declines in serum lamotrigine concentrations in pregnancy do not appear to predict epilepsy seizures, a first-of-its-kind study has found.
A secondary analysis of the AntiEpileptic drug Monitoring in PREgnancy (EMPiRE) study, conducted in 50 maternity units in the UK between November 2011 and May 2015, evaluated the association between serial lamotrigine concentrations and seizure occurrence, adjusting for baseline clinical predictors.
The researchers found no association between longitudinal serum lamotrigine concentrations and seizure occurrence (HR 0.421, p=0.087). Instead, the only independent predictor of seizure was the baseline daily dose of the drug (HR 1.005, p<0.001).
Routine monitoring of antiseizure medications was associated with increased drug exposure in newborns.
“Clinical management should continue to prioritise seizure history, adherence and clinical assessment,” they wrote. “Future research should identify whether some groups of pregnant women with epilepsy may still benefit from therapeutic drug monitoring.”
They noted lamotrigine was one of the most commonly prescribed drugs for women of childbearing age, but the optimal dose for seizure control varied between individuals.
Serum lamotrigine concentrations were known to decline during pregnancy because physiological changes increased drug clearance. Around one-third of pregnant women with epilepsy experienced changes in seizure frequency or reported seizures after previously been seizure-free, they added.
The researchers analysed pregnant women with epilepsy taking lamotrigine as monotherapy or polytherapy who had a baseline and at least one follow-up serum concentration measured before a seizure or up to six weeks postpartum.
Of more than 500 women recruited to the EMPiRE trial, 183 contributed data and 46 had seizures in pregnancy.
Women with serum drug levels that had fallen by 25% from baseline were randomised to therapeutic drug monitoring, in which clinicians reviewed levels and could adjust drug dose accordingly, or to clinical monitoring, where dose adjustments were based on clinical assessment alone.
The primary outcome was time to first seizure within pregnancy up to six weeks postpartum.
Clinical context key
Among the study’s limitations was the relatively small sample size, which limited subgroup and interaction testing, making it harder to determine whether predictive value differed between women on monotherapy versus polytherapy.
Moreover, because most seizures occurred early in pregnancy, few women had repeat serum measurements before the first event, reducing the model’s ability to evaluate the association between serum drug levels and seizure risk.
In addition, pre-pregnancy anti-seizure medication levels were rarely available, meaning the first pregnancy measurement was used as baseline, potentially underestimating reductions in lamotrigine concentrations. The researchers noted that this reflected routine clinical practice.
“Many women remain seizure-free despite large reductions in serum concentrations while some experience breakthrough seizures with only small changes in levels,” they noted. “This variability suggests that the link between serum concentration and seizure control may not be straightforward and that clinical context matters more than absolute drug levels.”
“Effective care depends on early identification of women at increased risk of seizures, coordination between obstetric and neurology services, and regular clinical review throughout pregnancy.”
The full findings were published in BMJ Neurology [link here].