[Methylphenidate-induced cytogenetic alterations?].
OBJECTIVE
Due to concerns that methylphenidate (MPH) might induce cytogenetic alterations in children, treatment with this drug is a controversial issue. The controversy arose following a report by El-Zein et al. (2005) of increased chromosomal aberrations, sister chromatid exchanges, and micronuclei in twelve children after three months of MPH treatment.


METHODS
The study by El-Zein is discussed with regard to current cytogenetic standards and earlier studies on the mutagenicity, clastogenicity, and carcinogenicity of MPH are reviewed.


RESULTS
Conclusions from the El-Zein study are limited due to methodological shortcomings. Results of animal studies on the mutagenicity and clastogenicity of MPH are inconsistent. While there was no indication of mutagenic effects in bacteria or mammalian cells, MPH might have some potential to induce clastogenic damage in mammalian cells. There was no evidence of carcinogenic activity in rats, while in mice the occurrence of hepatic neoplasms increased. In an epidemiological study, the incidence of cancers following MPH treatment was lower than had been expected.


CONCLUSIONS
Given the ambiguous findings of genetic toxicology studies in animals, the paucity of long-term toxicology data on MPH in humans is disquieting. Although it seems premature to conclude that MPH entails a mutagenic risk, the concern raised by El-Zein et al. warrants profound clarification.
Holtmann
Martin
M
Klinik für Psychiatrie und Psychotherapie des Kindes- und Jugendalters, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt. holtmann@em.uni-frankfurt.de
Kaina
Bernd
B
Poustka
Fritz
F
D000293:Adolescent; D000818:Animals; D015197:Carcinogenicity Tests; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D002648:Child; D006801:Humans; D008774:Methylphenidate / Q000633:toxicity*; D051379:Mice; D009152:Mutagenicity Tests; D051381:Rats; D012306:Risk
D000697:Central Nervous System Stimulants; D008774:Methylphenidate