Journal of the American Academy of Child & Adolescent Psychiatry
Volume 47, Issue 12 , Pages 1375-1383, December 2008

Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children With ADHD

Ms. Witt and Drs. Shelby and Kissling are with the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services; Drs. Itchon-Ramos, Chrisman, Ravi, and Kollins and Ms. Faircloth are with the Department of Psychiatry, Duke ADHD Program, Duke University Medical Center; Dr. Murli is with Covance Laboratories; and Dr. Mattison is with the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services

Accepted 3 July 2008.

Disclosure: Dr. Kollins received research support and/or honoraria/consulting fees from the following sources during the conduct of this study: Athenagen, Eli Lilly, Psychogenics, Pfizer, New River Pharmaceuticals, Shire Pharmaceuticals, National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, and Environmental Protection Agency. Dr. Chrisman received honoraria and was on the speakers' bureaus of Shire Pharmaceuticals and McNeil-PPC. The other authors report no conflicts of interest.

Abstract 

Objective

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.

Method

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.

Results

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.

Conclusions

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.

Key Words:  stimulant drugs , micronuclei , chromosome aberrations , sister chromatid exchanges , cohort study

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 This research was supported by the NIH/NICHD Best Pharmaceuticals for Children Act pediatric drug development program and the Intramural Research Program of the National Toxicology Program of the National Institute of Environmental Health Sciences.The authors thank Dr. Gregory Erexson, George Stojhovic, and Kelley Boyer for establishing, coordinating, and conducting the cytogenic analysis. The authors also thank the Duke ADHD Program psychologists for help in recruitment and enrollment, the Program's clinical trials team for assistance with the evaluation process during the screening period, and the Program's research assistants for invaluable help in the conduct of the study. The authors also thank Drs. Raymond Tice and Andrew Kligerman for fruitful discussions during preparation of this manuscript.Clinical trial registration information—Genetic Measurements in Blood Cells of Children Taking Adderall or Methylphenidate. URL: http://clinicaltrials.gov. Unique identifier: NCT00341029.

PII: S0890-8567(08)60136-7

doi:10.1097/CHI.0b013e3181893620

Journal of the American Academy of Child & Adolescent Psychiatry
Volume 47, Issue 12 , Pages 1375-1383, December 2008

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