Wirksamkeitsuntersuchung von Lamotrigin in der Epilepsie-Therapie

Abstract

Epilepsy is one of the most common neurological diseases and affects all age groups. It can be divided into focal, generalized and unclassifiable epilepsies depending on the brain region affected and on the etiology. Diagnosis is predominantly clinical, via EEG and cerebral imaging. The therapy consists primarily of antiepileptic drugs and secondarily of stimulation or surgical procedures. Lamotrigine is the antiepileptic drug of first choice for focal epilepsy and an alternative for generalized epilepsy. It is frequently used due to its broad spectrum of efficacy and favorable side effect profile. While the general effect on focal epilepsies is well documented, only a small number of studies have examined the relation between etiology and effectiveness of lamotrigine or differences in effective dosage. The aim of this work was to record the effectiveness of lamotrigine as a monotherapy and in combination with other drugs on different types of epilepsy. Furthermore, outcome with different effective dosages and effectiveness of different combination therapies was studied. In addition, it was investigated whether specific EEG findings are correlated with the effectiveness of lamotrigine and which side effects occur most frequently during treatment. For this purpose, the medical records from 254 patients who had been treated with lamotrigine for epilepsy at the University Medical Center Göttingen were retrospectively recorded and statistically evaluated. There were more women than men in the patient cohort and more patients with focal epilepsies than with generalized epilepsies. Lesional focal epilepsies were more common than focal epilepsies of unknown etiology. On average, patients with generalized epilepsy were younger than those with focal epilepsy and patients with lesional focal epilepsies were older than patients with focal epilepsies of unknown etiology. Statistically significant correlations between the EEG findings and the overall assessment of the success of the therapy were found for all types of epilepsy examined. Normal EEGs were recorded more frequently in patients without seizures during therapy with lamotrigine, whereas pathological EEGs were recorded more frequently in patients where lamotrigine did not prevent seizures. These results were most pronounced in lesional focal epilepsies. Adverse reactions to lamotrigine occurred significantly more frequently at doses at or above 600 mg. 39.4% of patients had side effects attributable to lamotrigine. The most common were dizziness, insomnia, sedation/fatigue, visual disturbance, ataxia, and tremor. A therapeutic effect was achieved in more than half of the patients with both lamotrigine as monotherapy and in combination therapy. Seizure prevention was more often achieved with monotherapy and the dosages required for therapeutic efficacy were lower than with combination therapy. In focal epilepsies of unknown etiology, lamotrigine monotherapy resulted in significantly more seizure prevention and fewer treatment failures than in generalized epilepsies. With a combination therapy, freedom from seizures was rarely accomplished in focal epilepsies, but a partial effect was often achieved. In focal epilepsies of unknown etiology, freedom from seizures was not only most frequently achieved with lamotrigine as monotherapy, but also almost exclusively at doses <400 mg. In only 4 out of 52 patients was a therapeutic effect achieved with higher doses. In comparison, 22 of 41 patients with lesional focal epilepsies were seizure-free or had a reduced seizure occurrence at doses ≥400 mg. In contrast to focal epilepsies, the treatment of generalized epilepsies with lamotrigine as a combination partner resulted in significantly more seizure-free outcomes and fewer treatment failures than with lamotrigine as monotherapy. In 19 of 30 patients, a therapeutic effect was also achieved with doses ≥400 mg. These findings underscore the superior efficacy of lamotrigine in focal epilepsies compared to general epilepsies, at least in those with no established lesional origin. However, patients with generalized epilepsy benefited comparatively more from combination therapy. Patients who only needed one antiepileptic drug required lower dosages for therapeutic efficacy than those with combination therapy, presumably because they represented a subset of less severe epilepsy that was easier to control. Patients with lesional focal epilepsies often required higher dosages for successful therapy than patients with focal epilepsies of unknown etiology. This suggests that the etiology influences the level of the effective dosage of lamotrigine therapy. These results also suggest that EEG studies have a certain predictive value for response to lamotrigine, especially in patients with lesional focal epilepsies. Further, particularly prospective studies will be required in order to validate these results and to study possible causal relationships between etiology and therapeutic outcome.