Midbari Yael, Ebert Tanya, Kosov Ira, Kotler Moshe, Weizman Abraham, Ram Anca
1 Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv, Israel .
J Child Adolesc Psychopharmacol. 2013 Oct;23(8):516-21. doi: 10.1089/cap.2013.0050. Epub 2013 Oct 10.
There are very few studies in the literature regarding clozapine use in children <13 years of age. In this retrospective chart review, we compared the safety of clozapine--as determined by hematological and cardiometabolic changes - to that of non-clozapine antipsychotics used in the treatment of childhood-onset schizophrenia (COS).
The clozapine treatment group (CTG) consisted of 17 COS patients (mean age 10.4 ± 2 years) who were hospitalized in a psychiatric ward between the years 2005 and 2012. The control group consisted of 19 COS patients (mean age 10.1 ± 1.4 years) who were hospitalized in the same ward during the same time period, and were treated with non-clozapine antipsychotics. A retrospective chart review was conducted. Hematological (white blood cells, absolute neutrophil count [ANC], red blood cells, platelets), metabolic (aspartate transaminase, alanine transaminase, triglycerides, total cholesterol, bilirubin) and cardiac (heart rate) values were extracted from the medical charts.
The average follow-up periods for the CTG and the control group were 332.9 ± 200.5 days and 291.7 ± 157 days, respectively. In the CTG, moderate neutropenia (ANC<1500/mm(3)) and mild neutropenia (1500/mm(3)<ANC<2000/mm(3)) were observed in two children (12%) and one child (6%), respectively. The neutropenia was transient in all cases. Treatment with clozapine was permanently discontinued only in one child (6%). There were no cases of agranulocytosis or severe infection in the CTG. In the control group, two children (11%) showed hematological abnormalities. Hyperlipidemia was observed in one child (6%) in the CTG at release from the hospital. Significantly more children (47%) in the CTG had tachycardia (heart rate>100 beats per minute) at release from the hospital, compared with only one child (5%) in the control group (p=0.006).
It appears that clozapine use in very early onset schizophrenia is safe. Although hematological adverse effects did occur in our study, the rates were not much higher than those seen in the control group. We found that the hematological abnormalities in the CTG were mostly transient, and that treatment with clozapine can be safely continued or renewed.
文献中关于13岁以下儿童使用氯氮平的研究非常少。在这项回顾性病历审查中，我们比较了氯氮平（根据血液学和心脏代谢变化确定）与用于治疗儿童期起病精神分裂症（COS）的非氯氮平抗精神病药物的安全性。
氯氮平治疗组（CTG）由2005年至2012年间在精神科病房住院的17例COS患者（平均年龄10.4±2岁）组成。对照组由同期在同一病房住院并接受非氯氮平抗精神病药物治疗的19例COS患者（平均年龄10.1±1.4岁）组成。进行了回顾性病历审查。从病历中提取血液学（白细胞、绝对中性粒细胞计数[ANC]、红细胞、血小板）、代谢（天冬氨酸转氨酶、丙氨酸转氨酶、甘油三酯、总胆固醇、胆红素）和心脏（心率）值。
CTG和对照组的平均随访期分别为332.9±200.5天和291.7±157天。在CTG中，分别有2名儿童（12%）和1名儿童（6%）出现中度中性粒细胞减少（ANC<1500/mm³）和轻度中性粒细胞减少（1500/mm³<ANC<2000/mm³）。所有病例中的中性粒细胞减少都是短暂的。仅1名儿童（6%）永久性停用氯氮平治疗。CTG中无粒细胞缺乏症或严重感染病例。在对照组中，2名儿童（11%）出现血液学异常。CTG中有1名儿童（6%）出院时出现高脂血症。与对照组仅1名儿童（5%）相比，CTG中出院时心动过速（心率>10每分钟0次）的儿童明显更多（47%）（p=0.006）。
看来在极早期起病的精神分裂症中使用氯氮平是安全的。虽然在我们的研究中确实发生了血液学不良反应，但其发生率并不比对照组高很多。我们发现CTG中的血液学异常大多是短暂的，氯氮平治疗可以安全地继续或重新开始。
