Children, Mice, Rats, and Ritalin

Although methylphenidate—the generic name for drugs including Ritalin, Concerta, and Metadate CD—has been prescribed for more than fifty years, surprisingly few studies have examined its possible side effects. One report in 1996 showed that the highest levels of methylphenidate tested caused liver tumors in male and female mice. But a similar study in rats showed no such tumors.

Still, the mouse study worried the late Marvin S. Legator, UTMB professor of environmental toxicology. After all, methylphenidate today is the most widely prescribed of a class of amphetamine-like drugs used to treat children with attention deficit and hyperactivity disorder (ADHD). In 1996 alone, more than ten million prescriptions were written for it, and methylphenidate sales soared some 500 percent during the 1990s.

Legator, who died last July, and his colleagues organized a small study of children newly diagnosed with ADHD who were prescribed methylphenidate. The researchers drew blood from the children before they began taking methylphenidate to get a baseline level of abnormalities in their chromosomes, the bodies within cells that carry the genes and genetic information. Then, three months after the kids started taking normal dosages of the drug, the researchers drew and tested the children’s blood a second time.

The results were startling: every single one of a dozen children treated with the drug who stayed on it for three months had three times as many chromosome abnormalities as they had before they started taking methylphenidate. Most of the abnormalities were chromosome breaks.

 “A higher frequency of aberrations is reported to be associated with an increased risk of cancer down the line,” says lead author Randa A. El-Zein, an assistant professor of epidemiology at the University of Texas M.D. Anderson Cancer Center in Houston, who performed the blood studies. “It was pretty surprising that all of the children taking methylphenidate showed an increase in chromosome abnormalities in a relatively short period of time.”

“This study doesn’t mean that these kids are going to get cancer,” principal investigator and senior author Legator stressed, “but it does mean they are exposed to an additional risk factor, assuming that this study holds up.” Of the fifty-three known human carcinogens, he says, forty-eight could be detected using the chromosome analysis methods El-Zein employed.

Reporting their discovery in the journal Cancer Letters, the researchers said this seems to be the first study addressing the potential chromosome-breaking effects associated with methylphenidate prescribed to children. The article was first made available online in February 2005.

Much larger studies at several medical centers are needed to confirm these results and to answer questions not addressed by it—including what happens when children stop taking methylphenidate. “Do the levels of chromosome abnormalities go back to normal?” El-Zein asks. “We don’t know.” —Tom Curtis