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.
| Witt, Kristine L; Shelby, Michael D; Itchon-Ramos, Nilda et al. (2008) Methylphenidate and amphetamine do not induce cytogenetic damage in lymphocytes of children with ADHD. J Am Acad Child Adolesc Psychiatry 47:1375-83 |
| Jacobson-Kram, David; Mattison, Donald; Shelby, Michael et al. (2008) Methylphenidate and chromosome damage. Cancer Lett 260:216-8 |
