Lamotrigine therapeutic thresholds

To evaluate therapeutic drug monitoring (TDM) of lamotrigine (LTG) with establishment of individual therapeutic thresholds (TT) in outpatients of a tertiary epilepsy centre on monotherapy.

In the outpatient clinic of the Danish Epilepsy Centre, Dianalund, all patients treated in 2004 with LTG monotherapy were identified. Patients who had not reported seizures or adverse reactions in the last 6 months were considered seizure free and well-medicated on LTG monotherapy, and were further evaluated. Plasma levels from routine LTG TDM obtained by reversed-phase high-pressure liquid chromatography (HPLC) during up-titration were used to calculate the TT for each patient as the mean of the highest subtherapeutic and the lowest therapeutic level.

Eighty-two patients undergoing LTG monotherapy were reported seizure free as defined above. In 34 the TT could not be calculated because they became seizure free on the first chosen dose. TTs of the remaining 48 patients ranged from 4.0 to 42.0 micromol/l. There were no differences between children and adults, and between generalized and localization-related epilepsies. The therapeutic levels of patients with undefined TT tended to be lower. The level-dose ratio in both groups varied only moderately indicating absence of major exogenous influences.

Even in patients of a tertiary referral centre only a minority had high TTs and needed therapeutic levels in a range where toxicity is increasingly observed. TDM appears useful in LTG treatment both for the establishment of individual reference ranges and for the identification of the individual level-to-dose ratio.