Abstracts

Rationale: Lamotrigine (LTG)is FDA approved for treatment of partial and generalized seizures. Previous studies demonstrate a a variable relationship between serum concentrations and clinical efficacy, some suggesting effective levels of 1-4 μg/mL. Current evidence suggests a wide therapeutic level of LTG ranging from 2 to 20 μg/mL. Literature suggests adverse effects that require dose changes in LTG are at levels <10 μg/mL. It has been suggest that higher levels can lead to additional efficacy in refractory patients. Our study attempts to correlate serum drug concentrations to the degree of seizure control. Methods: This was a retrospective chart review of patients seen in a tertiary care epilepsy center. Inclusion criteria were: minimum 16 years of age, primary diagnosis of epilepsy, and on LTG. Patients excluded were patients with non-epileptic events and patients on enzyme inducing AEDs (EIAEDs). In total, 51 serum LTG levels were obtained. After the removal of patients on both LTG and EIAED, the final N for LTG levels was 40. For purposes of analysis, the percentage reduction in seizure frequency (%RSF) was grouped into the following: 0% (No change), <50%, 51-75%, 76-100% (100%=No seizure). All analyses were performed using SPSS Ver 15.0 (Chicago, IL). Note: data collection is ongoing at the time of submission of this abstract.Results: In total, 40 LTG levels were analyzed. Those with %RSFs of 0%, <50%, 51-75%, and 76-100% showed mean serum LTG concentrations of 8.95 μg/mL, 11.28 μg/mL , 5.33 μg/mL and 5.56 μg/mL; respectively. ANOVA showed significant differences between the mean LTG serum levels for those in the <50% group and the 51-75%, 76-100% groups (p<0.05; CI=.69,11.21; 1.23, 10.21 respectively). A Spearman’s test showed a significant correlation between serum LTG levels and concurrent LTG doses (p<0.01). A comparison of the serum LTG monotherapy versus polytherapy was performed using the Mann-Whitney test for nonparametric data. The difference in mean serum LTG levels for patients undergoing monotherapy treatment (5.94 μg/mL) versus polytherapy treatment (9.89 μg/mL) was significant (p<0.01). Conclusions: Our study exhibits a significant correlation between the LTG dose and the LTG serum concentration. Those on polytherapy with non-enzyme inducing agents also had significantly higher LTG levels than those on LTG alone. A relationship did exist between serum LTG drug levels and the %RSF. Given that the LTG levels were significantly lower in the 75% and 100% (%RSF) groups in comparison to the 50% group, higher doses of LTG may not be needed for seizure control. This suggests that clinicians may not need to 'dose to effect'. Our study suggests, therapeutic range of serum LTG levels are higher than previously reported (>5 μg/mL).