Does methylphenidate cause a cytogenetic effect in children with attention deficit hyperactivity disorder?

Abstract

Background and objective: Attention deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents (6-12% affected). Treatment with methylphenidate (MPH) in the United States has increased to a current prescription rate of > 5 million per year. However, a 2005 study by El-Zein and co-workers [Cancer Lett 230:284-291] reporting a 3-fold increase in genomic damage in all 12 analyzed children after 3 months of therapy with MPH resulted in much concern about potential carcinogenic effects. Here we provide new information concerning the cytogenetic effect of MPH in children.

Design, participants, and methods: In a prospective study, we analyzed the genomic damage in children with ADHD (initial sample size 38 children) before and 1 (30 children), 3 (21 children), and 6 (8 children) months after initiation of MPH therapy. In addition, we investigated a group of 9 children receiving chronic MPH therapy. Patients were recruited within a study of our Clinical Research Group on ADHD in the Department of Child and Adolescent Psychiatry and Psychotherapy of the University of Würzburg. Assessment and treatment of patients were performed during inpatient or outpatient health care. The measure for genomic damage was the frequency of micronuclei, a subset of chromosomal aberrations, in peripheral lymphocytes.

Results: MPH treatment resulted in no significant alteration in the micronucleus frequency.

Conclusions: Because the findings published in 2005 by El-Zein and co-workers could not be replicated, the concern regarding a potential increase in the risk of developing cancer later in life after long-term MPH treatment is not supported.

Figure 1

Individual frequencies of micronucleated peripheral lymphocytes of children with ADHD before and after MPH treatment at three follow-up intervals. BNC, binucleated cells. In group A, all children were included for whom only a basal value (before start of medication) was obtained. The groups B, C, and D included patients for whom values after 1 month (follow-up 1), 3 months (follow-up 2), and 6 months (follow-up 3) were obtained. Data were sorted according to the heights of the column for the basal values.