소아청소년기 결신 발작에서 일차 약제로서 Lamotrigine의 치료 효용에 관한 연구
Lamotrigine as a First-line Monotherapy in Children with Absence Seizures
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목 적:저자들은 소아청소년기의 결신 발작에서 lamotrigine을 1차 약제로 투여하여 경련 발작의 감소 정도와 부작용을 살펴 기존 약물과 비교하여 그 효과와 안전성을 밝히고자 하였다. 방 법:2000년 1월부터 2009년 12월까지 서울아산병원 소아청소년과 신경분과 외래를 통해 새롭게 소아청소년기 결신 발작으로 진단 된 환아 중, lamotrigine을 1차 약제로 투여 한 36명의 환아를 대상으로 하였다. 이들은 결신 발작의 전형적인 임상상과 3 Hz의 특징적 뇌파소견을 기준으로 모집되었다. Lamotrigine은 하루 10 mg로 시작하여 몸무게당 10mg에 도달하거나 발작이 조절될 때까지 증량하였으며 투여에 따른 발작 감소율, 사용에 따른 부작용 등을 후향적으로 조사하였다. 결과:전체 36명의 환자 중 31명이 소아기 결신 발작이었고, 5명은 청소년기 결신 발작이었다. 초기 투여 후 4주간의 적정 기간동안 30명(83.3%)에서 50% 이상의 발작 감소를 나타내었으며 평균 8.3주간의 투여 후 23명(63.9%)에서 발작이 완전히 조절되었고, 이들 중 12주간의 추적 기간 동안 발작이 완전히 조절 된 누적 환자 수는 각각 4주차에 6명(16.7%), 8주차에는 18명(50.0%), 12주차에 23명(63.9%)으로 나타났다. 평균 12개월 경 추적한 뇌파 검사에서는 33.3%(12명)에서 정상화되는 소견을 보였다. 약물의 증량에도 발작이 조절되지 않아 valproic acid나 ethosuximide 등 다른 약물의 병합 치료를 요했던 경우는 4명(11.1%)에서 관찰되었다. 피부 발진이나 두통, 현기증 등의 부작용이 보고되었으나 대부분의 경우 증상이 경미하여 약물 치료의 지속에는 영향을 미치지 않았다. 결론:소아청소년기 결신 발작에서 lamotrigine은 발작 조절에 효과적이며 심각한 부작용의 빈도가 비교적 낮아 1차 단독약제로서 장기적으로 안전하게 투여될 수 있을 것으로 전망된다.
Abstract
Purpose:Typical absence seizures are characterized by the daily presentation of frequent staring and typical 3Hz spike and wave discharges in otherwise healthy children. Typical absence seizures can present in childhood absence epilepsy and related syndromes. Lamotrigine (LTG) has been anecdotally used as a monotherapy for this seizure type; however, the efficacy and tolerability has remained unknown. The aim of this study was to evaluate the efficacy, tolerability, and long-term outcome of LTG in patients with newly diagnosed typical absence seizures. Methods:Medical records of 36 patients having newly diagnosed typical absence seizures were analyzed. Patients were included based on the history of typical absence seizures and 3 Hz spike and wave discharges in interictal EEG. LTG was administered at a starting dose of 10 mg/day and increased by 10 mg/week until seizure freedom or reaching a dose of 10 mg/kg/day. Results:Thirty-one patients had childhood absence epilepsy (CAE) and five had juvenile absence epilepsy (JAE). Thirty patients (83.3%) experienced more than 50% reduction of seizure frequency after 4 weeks of initial titration. Twenty-three patients (63.9%) achieved seizure freedom for 4 weeks after a mean duration of 8.3 weeks of treatment, and the cumulative numbers of patients with seizure freedom were 6 (16.7%), 18 (50.0%), and 23 (63.9%) within 4, 8, and 12 weeks, respectively. After 12 months of treatment, 12 patients (33.3%) showed normalized EEG findings, and their symptoms also disappeared. Four patients had uncontrolled seizures despite of dose increment and consequently needed additional treatment with valproic acid or ethosuximide. Most adverse effects, including skin rash (n=4), headache (n=1), and dizziness (n=1), were transient and tolerable. Conclusion:Lamotrigine, as a first-line monotherapy in newly diagnosed patients with typical absence seizures, could be safely used with good efficacy in seizure control.
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