Abstract
Correlating Lamotrigine Serum Concentrations with Tolerability in Patients with Epilepsy Hirsch LJ, Weintraub D, Du Y, Buchsbaum R, Spencer HT, Hager M, Straka T, Bazil CW, Adams DJ, Resor SR Jr, Morrell MJ Neurology 2004;63:1022–1026 Objective To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy. Methods The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels. Results In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic, and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels ( P < 0.0001): With levels less than 5.0 μg/mL, 7% of patients were toxic; with levels of 5 to 10 μg/mL, 14%; with 10 to 15 μg/mL, 24%; with 15 to 20 μg/mL, 34%; and with more than 20 μg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of more than 20 μg/mL. Conclusions A correlation exists between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 μg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 μg/mL). An initial target range of 1.5 to 10 μg/mL is suggested, although higher levels, up to more than 20 μg/mL, are often tolerated and can lead to additional efficacy in refractory patients.