Cytogenetic damage in ADHD children treated with methylphenidate or Adderall

这项研究旨在澄清早期的一项初步研究的结果，该研究报告了12名被诊断为注意力缺陷多动障碍(ADHD)的儿童(6-12岁)在接受以哌醋甲酯为基础的药物治疗3个月后，淋巴细胞染色体损伤的三项指标显著增加(El-Zein等人，2005年)。这项研究中显著的方案缺陷引起了人们对结论的担忧(Preston等人，2005年)，并促使设计了这项重复研究，采用了更广泛的方案并仔细监测了数据收集。研究对象的招募和登记是通过杜克大学医学中心ADHD计划进行的。 在这项研究中，我们调查了早期初步研究中分析的相同的3种细胞遗传学损伤指标(微核、姐妹染色单体交换、染色体异常)。淋巴细胞中这三个终点的分析遵循了普遍建立的方案，所有的实验室程序都是在良好的实验室实践指南下进行的。我们使用相同的分析程序：在药物治疗开始前测量每个受试者的淋巴细胞样本中的3个细胞遗传学终点，然后在药物治疗3个月后再次测量。由于Adderall是苯丙胺盐的一种组合，越来越多地用于儿童ADHD的治疗，目前约占ADHD患者所有新药处方的50%，因此在该方案中增加了对服用Adderall的儿童淋巴细胞细胞遗传学终点的调查，以向临床医生和患者提供比较数据。目前还没有已发表的Adderall在人类中的细胞遗传学数据。阿得拉和哌醋甲酯被认为是同样有效的，医生的选择是决定为任何特定患者开出哪种处方的因素。 我们的目标是招募60名儿童，年龄6-12岁，无论性别、种族和种族，被杜克大学的ADHD工作人员诊断为ADHD，任何亚型，对其进行药物治疗的兴奋剂。一半的儿童开始接受以哌醋甲酯为基础的治疗，一半的儿童开始使用Adderall治疗。分配给研究组是随机的，因为这两种药物疗法被认为是可以互换的。没有必要排除ADHD亚型，因为治疗、剂量和ADHD亚型之间没有相关性。选择这个数量的受试者(60名)是为了让我们有足够的能力来检测与治疗相关的细胞遗传学变化或支持负面观察。 如果研究对象没有共病心理疾病，没有违禁兴奋剂治疗的身体状况，患有ADHD药物幼稚，并且在过去3个月内没有接受过诊断X光检查，那么他们有资格参加研究。所有研究对象或其法定监护人都提供了知情的书面同意。 截至2008年8月120日，本研究已完成。对数据进行了分析，报告结果的手稿已被接受，将发表在《美国儿童和青少年精神病学杂志》上。结果将在手稿出版时公开。

This study was designed to clarify results from an earlier pilot study that reported significant increases in three measures of chromosomal damage in lymphocytes of 12 children (ages 6-12) diagnosed with Attention DeficitHyperactivity Disorder (ADHD), following 3 months of treatment with methylphenidate-based medications (El-Zein et al., 2005). Significant protocol deficiencies in this study raised concerns about the conclusions (Preston et al., 2005) and prompted the design of this repeat study that employed a more extensive protocol and carefully monitored data collection. Recruitment and enrollment of study subjects occurred through the Duke University Medical Center ADHD Program. In this study, we investigated the same 3 measures of cytogenetic damage (micronuclei, sister chromatid exchanges, chromosomal aberrations) that were analyzed in the earlier pilot study. Universally established protocols for analysis of these three endpoints in lymphocytes were followed, and all laboratory procedures were conducted under Good Laboratory Practice guidelines. We used the same schedule of analysis: measurement of the 3 cytogenetic endpoints in lymphocyte samples obtained from each subject prior to the initiation of drug treatment, and then again after 3 months of pharmacotherapy. Because Adderall, a combination of amphetamine salts, is increasingly used in the treatment of ADHD in children and now constitutes approximately 50% of all new drug prescriptions for ADHD patients, an investigation of cytogenetic endpoints in lymphocytes of Adderall-treated children was added to this protocol to provide comparative data to clinicians and to patients. There are currently no published cytogenetic data for Adderall in humans. Adderall and methylphenidate are considered equally effective and physician choice is the factor determining which is prescribed for any particular patient. Our goal was to enroll 60 children, age 6-12 years inclusive, of either sex, and of any ethnicity and race, diagnosed by Duke ADHD staff with ADHD, any subtype, for whom pharmacological treatment with stimulants was indicated. Half the children began treatment with methylphenidate-based therapy and half the children began treatment with Adderall. Assignment to study group was random because the two drug therapies are considered to be interchangeable. No exclusions by ADHD subtype were necessary because there is no correlation between treatment, dose, and ADHD subtype. This number of subjects (60) was selected to give us sufficient power to detect treatment-related cytogenetic changes or support negative observations. Study subjects were eligible for enrollment if they had no co-morbid psychological conditions, no physical conditions that contraindicated stimulant treatment, were ADHD-drug naive, and had not received diagnostic x-rays in the past 3 months. All study subjects or their legal guardians provided informed written consent. As of August 120, 2008, this study is complete. The data have been analyzed and the manuscript reporting the results has been accepted for publication in the Journal of the American Academy of Child and Adolescent Psychiatry. Results will be publicly available when the manuscript is published.