Dose “Ceiling” May Exist for Epilepsy Treated With Lamotrigine

Scientist looking at blood specimen
Scientist looking at blood specimen
A "ceiling" may exist for lamotrigine therapy above which remission from seizures may be unlikely.

Patients with epilepsy who are in seizure remission have lower serum levels of lamotrigine compared with patients who experience ongoing seizures and have higher daily lamotrigine dosages, according to findings from a retrospective study published in Epilepsy & Behavior.

Researchers retrospectively evaluated epileptic adults (n=93). Of these patients, 10 were in remission of seizures. Patients in remission presented with significantly lower lamotrigine serum levels compared with patients experiencing ongoing seizures (median, 2.3 mg/L [range, 0.7-8.2] vs median, 5.4 mg/L [range, 1.1-18.2], respectively; P =.008).

The distribution of lamotrigine dosages significantly differed among the 2 groups (median, 175 vs 300 mg; P =.03). In addition, the investigators used an analysis of variance model to demonstrate that patients with continual seizures had twice the mean serum concentration of lamotrigine when compared with remission patients (relative increase by a factor of 2.05; 95% CI, 1.3–3.3; P =.003).

In addition, the investigators found that lamotrigine monotherapy was associated with lower blood levels of the medication vs polytherapy (median, 3.8 mg/L [range, 1.1-14.4] vs median, 6.0 mg/L [range, 1.6-18.2]; P =.005) in patients with ongoing seizures.

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The study’s retrospective design and lack of systematic collection of samples represents potential limitations of this study. The researchers also suggest the possibility of natural remission of the disease in some patients and the subsequent lack of treatment efficacy, which may have played a role in the observed low lamotrigine serum levels.

A ceiling serum level of lamotrigine associated with remission, according to the investigators, may “help to rationalise the titration of the medication in drug naïve patients with epilepsy” or prompt medication switch.


D’Anto J, Wnuk W, Rossetti AO, et al. Lamotrigine serum levels: ceiling effect in people with epilepsy in remission? Epilepsy Behav. 2017;74:41-44.