Devinsky O, Honigfeld G, Patin J
Department of Neurology, Hospital for Joint Diseases, New York University School of Medicine, NY 10003.
Neurology. 1991 Mar;41(3):369-71. doi: 10.1212/wnl.41.3.369.
Clozapine is an atypical antipsychotic drug with minimal extrapyramidal toxicity recently approved by the Food and Drug Administration for hard-to-treat schizophrenic patients. We reviewed information on 1,418 patients treated with clozapine in the United States between 1972 and 1988. Forty-one of 1,418 (2.8%) patients had generalized tonic-clonic seizures during treatment with clozapine. Life-table analysis predicts a cumulative 10% risk of seizures after 3.8 years of treatment. Clozapine-related seizures appear to be dose-related. High-dose therapy (greater than or equal to 600 mg/day) was associated with a greater risk of seizures (4.4%) than medium (300 to 600 mg/day; 2.7%) or low doses (less than 300 mg/day; 1.0%). Also, rapid upward titration may increase seizure risk. Thirty-one of 41 patients were successfully continued on clozapine despite seizure occurrence, either with reduction of dose or addition of an antiepileptic medication. Recognition and treatment of clozapine-related seizures will become increasingly important as its use grows in the 1990s.
氯氮平是一种非典型抗精神病药物，锥体外系毒性极小，最近被美国食品药品监督管理局批准用于治疗难治性精神分裂症患者。我们回顾了1972年至1988年间在美国接受氯氮平治疗的1418例患者的信息。1418例患者中有41例（2.8%）在氯氮平治疗期间发生全身性强直阵挛性癫痫发作。生存分析预测，治疗3.8年后癫痫发作的累积风险为10%。氯氮平相关癫痫发作似乎与剂量有关。高剂量治疗（大于或等于600毫克/天）与癫痫发作风险（4.4%）高于中等剂量（300至600毫克/天；2.7%）或低剂量（小于300毫克/天；1.0%）有关。此外，快速增加剂量可能会增加癫痫发作风险。41例患者中有31例尽管发生了癫痫发作，但通过减少剂量或添加抗癫痫药物，仍成功继续使用氯氮平。随着氯氮平在20世纪90年代的使用增加，认识和治疗氯氮平相关癫痫发作将变得越来越重要。
