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对患有注意力缺陷多动障碍的儿科患者进行哌甲酯治疗的细胞遗传学评估。

Cytogenetic assessment of methylphenidate treatment in pediatric patients treated for attention deficit hyperactivity disorder.

作者信息

Tucker James D, Suter Willi, Petibone Dayton M, Thomas Robert A, Bailey Nicole L, Zhou Yinong, Zhao Yanxing, Muniz Rafael, Kumar Vinod

机构信息

Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202-3917, United States.

出版信息

Mutat Res. 2009 Jun-Jul;677(1-2):53-8. doi: 10.1016/j.mrgentox.2009.05.005. Epub 2009 May 22.

Abstract

Methylphenidate (MPH, Ritalin), has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the FDA over 50 years ago. Diagnoses of pediatric patients with ADHD and the administration of MPH to treat the symptoms have increased in prevalence in recent years. A 2005 study by El-Zein et al. reported statistically significant increases in cytogenetic anomalies including chromosomal aberrations (CA), micronuclei (MN) and sister chromatid exchanges (SCEs) in peripheral blood lymphocytes cultured from pediatric patients treated for 3 months with MPH. These findings led to wide-spread concern regarding the potential for genotoxic risks associated with prolonged administration of MPH. The study described in the present paper was designed to repeat the El-Zein effort with a much larger sample size. The subjects (N = 109) were randomized into two groups: one treated with MPH as well as behavior therapy, the other was a control group that received behavior therapy only. We evaluated CAs, MN, and SCEs in peripheral blood lymphocytes in samples obtained prior to therapy and after 3 months of treatment with MPH. The data were analyzed using a Poisson regression model with a generalized estimating equation method adjusted for several covariates including time, treatment-by-time interaction, sex, and age group. The log(e) rate ratios of the MPH plus behavior therapy and behavior therapy groups were compared. The frequencies of CAs, MN, and SCEs were not increased in the MPH plus behavior therapy group when compared to the behavior therapy group only (p = 0.53, 0.28, 0.81, respectively). These results provide evidence in a large cohort that MPH does not induce cytogenetic anomalies in children, in contrast to the findings of the El-Zein study.

摘要

哌甲酯(MPH,利他林)自50多年前获得美国食品药品监督管理局(FDA)批准以来,一直被用于治疗注意力缺陷多动障碍(ADHD)。近年来,被诊断患有ADHD的儿科患者数量以及使用MPH治疗症状的情况都有所增加。2005年,埃尔 - 泽因等人的一项研究报告称,在接受MPH治疗3个月的儿科患者外周血淋巴细胞中,细胞遗传学异常(包括染色体畸变(CA)、微核(MN)和姐妹染色单体交换(SCE))在统计学上有显著增加。这些发现引发了人们对长期使用MPH可能产生的遗传毒性风险的广泛关注。本文所述的研究旨在以更大的样本量重复埃尔 - 泽因的研究。研究对象(N = 109)被随机分为两组:一组接受MPH治疗以及行为疗法,另一组为仅接受行为疗法的对照组。我们评估了治疗前和MPH治疗3个月后的样本中外周血淋巴细胞中的CA、MN和SCE。使用泊松回归模型对数据进行分析,该模型采用广义估计方程方法,并针对包括时间、治疗与时间的交互作用、性别和年龄组等多个协变量进行了调整。比较了MPH加行为疗法组和行为疗法组的log(e)率比。与仅行为疗法组相比,MPH加行为疗法组的CA、MN和SCE频率并未增加(p值分别为0.53, 0.28, 0.81)。与埃尔 - 泽因研究的结果相反,这些结果在一个大型队列中提供了证据,表明MPH不会在儿童中诱发细胞遗传学异常。

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