The genetic toxicity of methylphenidate: A review of the current literature

Suzanne M. Morris, Dayton M. Petibone, Wei Jiun Lin, James J. Chen, Benedetto Vitiello, Kristine L. Witt, Donald R. Mattison

Research output: Contribution to journalArticle

Abstract

Attention deficit/hyperactivity disorder (ADHD), a common children's behavioral disorder, is characterized by inattention, hyperactivity and impulsivity. The disorder is thought to stem from abnormalities in the catecholamine pathway and the symptoms of the disorder have been successfully treated with methylphenidate (MPH) since the FDA approved the drug in the 1950s. MPH underwent the appropriate safety testing as part of the FDA approval process; however, a publication in 2005 that reported significant increases in cytogenetic damage in the lymphocytes of MPH-treated pediatric patients caused concern for patients and their families, the pharmaceutical industry and regulatory agencies. This communication will review the many studies that were subsequently initiated worldwide to address the genetic safety of MPH in both animal models and human subjects. Animal experiments broadened the study protocols used in the 2005 investigation to include a wider dose-range, a longer treatment period and automated scoring of biological endpoints, where possible, to reduce observer bias. The human subject studies replicated the experimental design used in the 2005 study, but increased the treatment periods and the sizes of the study populations. Neither the laboratory animal nor human subject studies found an increase in any of the measures of genetic damage that were evaluated. Taken together, these new studies are consistent with the original safety evaluation of the FDA and do not support the hypothesis that MPH treatment increases the risk of genetic damage in ADHD patients. Published 2012. This article is a US Government work and is in the public domain in the USA. The symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) are effectively treated with methylphenidate (MPH). In 2005, reported increases in cytogenetic damage in the lymphocytes of MPH-treated pediatric patients caused world-wide concern. Numerous studies were initiated to verify or refute the findings. As reviewed in this communication, neither the laboratory animal nor human subject studies found an increase in MPH-induced genetic damage. The subsequent studies do not support the initial hypothesis that MPH treatment increases the risk of genetic damage in ADHD patients. 2012. This article is a US Government work and is in the public domain in the USA.

Original languageEnglish (US)
Pages (from-to)756-764
Number of pages9
JournalJournal of Applied Toxicology
Volume32
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

Fingerprint

Methylphenidate
Toxicity
Attention Deficit Disorder with Hyperactivity
Animals
Pediatrics
Lymphocytes
Public Sector
Laboratory Animals
Safety
Cytogenetics
Safety testing
Observer Variation
Impulsive Behavior
Communication
Drug Industry
Therapeutics
Population Density
Pharmaceutical Preparations
Design of experiments
Catecholamines

Keywords

  • ADHD
  • Chromosome damage
  • Methylphenidate
  • Mutation

ASJC Scopus subject areas

  • Toxicology

Cite this

Morris, S. M., Petibone, D. M., Lin, W. J., Chen, J. J., Vitiello, B., Witt, K. L., & Mattison, D. R. (2012). The genetic toxicity of methylphenidate: A review of the current literature. Journal of Applied Toxicology, 32(10), 756-764. https://doi.org/10.1002/jat.2721

The genetic toxicity of methylphenidate : A review of the current literature. / Morris, Suzanne M.; Petibone, Dayton M.; Lin, Wei Jiun; Chen, James J.; Vitiello, Benedetto; Witt, Kristine L.; Mattison, Donald R.

In: Journal of Applied Toxicology, Vol. 32, No. 10, 10.2012, p. 756-764.

Research output: Contribution to journalArticle

Morris, SM, Petibone, DM, Lin, WJ, Chen, JJ, Vitiello, B, Witt, KL & Mattison, DR 2012, 'The genetic toxicity of methylphenidate: A review of the current literature', Journal of Applied Toxicology, vol. 32, no. 10, pp. 756-764. https://doi.org/10.1002/jat.2721
Morris SM, Petibone DM, Lin WJ, Chen JJ, Vitiello B, Witt KL et al. The genetic toxicity of methylphenidate: A review of the current literature. Journal of Applied Toxicology. 2012 Oct;32(10):756-764. https://doi.org/10.1002/jat.2721
Morris, Suzanne M. ; Petibone, Dayton M. ; Lin, Wei Jiun ; Chen, James J. ; Vitiello, Benedetto ; Witt, Kristine L. ; Mattison, Donald R. / The genetic toxicity of methylphenidate : A review of the current literature. In: Journal of Applied Toxicology. 2012 ; Vol. 32, No. 10. pp. 756-764.
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