奥卡西平治疗儿童难治性癫痫的自身对照性研究

Self-control Study of Oxcarbazepine for the Treatment of Childhood Refractory Epilepsy

目的观察奥卡西平（OXC）治疗儿童难治性癫痫的长期疗效、耐受性和安全性。方法应用奥卡西平（OXC）治疗31例难治性癫痫患儿,起始剂量为4-5 mg/（kg·d^-1）,维持剂量为25-45 mg/kg·d^-1,以治疗前3个月癫痫发作频度为对照,对治疗后12个月内的疗效、不良反应、耐受性及安全性进行自身对比观察。结果应用OXC后6个月、12个月后,患儿发作频率均较用药前明显减少,发作频率减少≥50%的患儿占45.2%（14/31）,用药前后差异有统计学意义（P〈0.05）。用药后6个月与12个月发作频率比较差异无统计学意义。不良反应的发生率为12.9%（4/31）,因不良反应和经济原因退出观察者2例（5.88%）。常见的不良反应为乏力、头晕、头痛、恶心、纳差、皮疹。结论奥卡西平治疗儿童难治性癫痫疗效明显、稳定、不良反应轻、耐受性好、安全性高。在年龄小于5岁的患儿中应用OXC的安全性有待大样本研究。

Objective To evaluate the long-term efficacy, tolerability and safety of oxcarbazepine （OXC） in children with refractory epilepsy. Methods Thirty-one patients with refractory epilepsy were enrolled in an open add-on study with oxcarbazepine （OXC） to evaluate its long-term efficacy, tolerability and safety. Criteria of enrolment： （1） Diagnosed refractory epilepsy by clinic and electroencephalogram in the pediatrics epilepsy outpatient service of Tiantan Hospital. （2） Aged 3 - 15 years. （3） Criteria for refractory epilepsy： the blood concentration of anti-epileptic drugs in the normal range for at least 2 years by taking the first grade anti-epileptic drugs regularly for at least 2 years, but failed to control seizure and improve the everyday life, with episodic attacks of over 4 times per month. Excluding criteria： （1） Tumor and systematically deteriorating diseases of central nervous system. （2） Accompanying heart, liver, kidney, thyroid gland or blood diseases. （3） Carbamazepine allergy. （4） Filed to be followed up regularly. The treatment course was 12 months. The investigators should know about the currentry taking anti-epileptic drugs, frequencies and types of attacks three month before starting the investigation. The items examined included nerve image, electroencephalogram and laboratory tests. OXC was added to the current anti-epileptic drugs. The initial dose was 4 - 5 mg/（ kg·d^-1 ）. The dosage was increased by one time dose every 2 weeks, and the increment should not exceed 10 mg/（ kg ·d^-1 ）. The maintenance dose was （ 25 - 45 ） mg/（ kg·d^-1 ）. The seizure frequencies, adverse events three months before and twelve months after therapy were compared with the seizure frequencies of the in 12 weeks taken as the base line, and the observed results were rank remarkably efficient （the frequency decrement ≥ 75% ）; efficiency （the frequency decrement ≥50% ） ; not efficiency： the frequency decrement 〈 50% ; and deteriorate（ the frequency increased by≥25% ）. The blood and urine routines, the heart, liver and kidney functions, serum lipid and sodium levels, blood concentrations of anti-epileptic drugs, and electroencephalograms before and after therapy were compared also. Results Of the 31 patients, there were 13 partial seizure cases, 7 generalized seizure cases, 9 symptomatic generalized seizure cases and 2 lennox-Gastaut syndrome cases. At 6 months of treatment, oxcarbazepine（OXC） can significantly reduce seizure frequency compared with the pre-OXC period. It seemed that oxcarbazepine（OXC） was most efficacious in partial seizure. It showed that the seizure frequencies before and after therapy were significantly different （ P 〈 0.05 ）. However, there wa significant difference at 6 and 12 months after therapy （ P 〉 0.05 ）. Five patients （ 5/31, 16% ） became seizure-free, three patients（ 3/31, 9.7% ） remarkably efficient, six patients （6/31, 19.4% ） were efficient. The total effective rates （seizure frequency decreased by ≥50% were 14/31 （45.2%）. In addition, the numbers of interictal epilepsy discharge in EEG of 16 patients were decreased after OXC administration compared with with pre-OXC period. Two patients had dropped out because of economic problem and/or adverse events. Adverse reactions were found in 12.9% （4/31） of patients, the common adverse events were dizziness, headache, sommolence, nausea, fatigue and rashes. Adverse reactions were generally mild, and disappeared when dose was increased slowly. Conclusion The efficacy of OXC is sustained with good safety and tolerability profiles during the treatment of 12 months in children with refractory epilepsy. Safety of OXC in younger children（ ≤50 years old） need to be further validated.