Witt Kristine L, Shelby Michael D, Itchon-Ramos Nilda, Faircloth Melissa, Kissling Grace E, Chrisman Allan K, Ravi Hima, Murli Hemalatha, Mattison Donald R, Kollins Scott H
National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Triangle Park, NC 27709, USA.
J Am Acad Child Adolesc Psychiatry. 2008 Dec;47(12):1375-83. doi: 10.1097/CHI.0b013e3181893620.
In response to previously published findings of methylphenidate-induced chromosomal changes in children, this study was designed to determine whether methylphenidate- or amphetamine-based drugs induce chromosomal damage (structural aberrations, micronuclei, and sister chromatid exchanges) in peripheral blood lymphocytes of children with attention-deficit/hyperactivity disorder after 3 months of continuous treatment.
Stimulant drug-naïve subjects, 6 to 12 years of age, in good overall health, and judged to be appropriate candidates for stimulant therapy based on rigorously diagnosed ADHD using DSM-IV criteria, were randomized into two open-label treatment groups (methylphenidate or mixed amphetamine salts). Each subject provided a blood sample before initiation of treatment and after 3 months of treatment. Pretreatment and posttreatment frequencies of chromosomal aberrations, micronuclei, and sister chromatid exchanges were determined for each subject.
Sixty-three subjects enrolled in the study; 47 subjects completed the full 3 months of treatment, 25 in the methylphenidate group and 22 in the amphetamine group. No significant treatment-related increases were observed in any of the three measures of cytogenetic damage in the 47 subjects who completed treatment or the 16 subjects who did not.
Earlier findings of methylphenidate-induced chromosomal changes in children were not replicated in this study. These results add to the accumulating evidence that therapeutic levels of methylphenidate do not induce cytogenetic damage in humans. Furthermore, our results indicate that amphetamine-based products do not pose a risk for cytogenetic damage in children.
针对先前发表的关于哌醋甲酯引起儿童染色体变化的研究结果，本研究旨在确定连续治疗3个月后，哌醋甲酯或苯丙胺类药物是否会在患有注意力缺陷多动障碍的儿童外周血淋巴细胞中诱发染色体损伤（结构畸变、微核和姐妹染色单体交换）。
将年龄在6至12岁、总体健康状况良好、根据严格按照《精神疾病诊断与统计手册》第四版标准诊断为注意力缺陷多动障碍且被判定为适合接受兴奋剂治疗的未使用过兴奋剂药物的受试者，随机分为两个开放标签治疗组（哌醋甲酯组或混合苯丙胺盐组）。每位受试者在治疗开始前和治疗3个月后提供血样。测定每位受试者治疗前和治疗后染色体畸变、微核和姐妹染色单体交换的频率。
63名受试者参与了该研究；47名受试者完成了全部3个月的治疗，其中哌醋甲酯组25名，苯丙胺组22名。在完成治疗的47名受试者或未完成治疗的16名受试者中，三项细胞遗传学损伤指标均未观察到与治疗相关的显著增加。
本研究未重复先前关于哌醋甲酯引起儿童染色体变化的研究结果。这些结果进一步证明了越来越多的证据表明，哌醋甲酯的治疗剂量不会在人类中诱发细胞遗传学损伤。此外，我们的结果表明，苯丙胺类产品不会对儿童造成细胞遗传学损伤风险。
