Cytogenetic assessment of methylphenidate treatment in pediatric patients treated for attention deficit hyperactivity disorder.

Methylphenidate (MPH, Ritalin), has been prescribed to treat attention deficit/hyperactivity disorder (ADHD) since its approval by the FDA over 50 years ago. Diagnoses of pediatric patients with ADHD and the administration of MPH to treat the symptoms have increased in prevalence in recent years. A 2005 study by El-Zein et al. reported statistically significant increases in cytogenetic anomalies including chromosomal aberrations (CA), micronuclei (MN) and sister chromatid exchanges (SCEs) in peripheral blood lymphocytes cultured from pediatric patients treated for 3 months with MPH. These findings led to wide-spread concern regarding the potential for genotoxic risks associated with prolonged administration of MPH. The study described in the present paper was designed to repeat the El-Zein effort with a much larger sample size. The subjects (N = 109) were randomized into two groups: one treated with MPH as well as behavior therapy, the other was a control group that received behavior therapy only. We evaluated CAs, MN, and SCEs in peripheral blood lymphocytes in samples obtained prior to therapy and after 3 months of treatment with MPH. The data were analyzed using a Poisson regression model with a generalized estimating equation method adjusted for several covariates including time, treatment-by-time interaction, sex, and age group. The log(e) rate ratios of the MPH plus behavior therapy and behavior therapy groups were compared. The frequencies of CAs, MN, and SCEs were not increased in the MPH plus behavior therapy group when compared to the behavior therapy group only (p = 0.53, 0.28, 0.81, respectively). These results provide evidence in a large cohort that MPH does not induce cytogenetic anomalies in children, in contrast to the findings of the El-Zein study.