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Ritalin May Last Longer Than Thought

Drug may affect brain after dose has worn off

MONDAY, Nov. 12, 2001 (HealthDayNews) -- The effects of Ritalin, a drug commonly prescribed for children with attention deficit hyperactivity disorder, may last longer than expected.

Contrary to current belief that Ritalin has only short-term effects, new research indicates that the drug, known generically as methylphenidate, may affect brain function after a dose has worn off. The researchers, whose findings stem from studies with rats, say they do not yet know how great the effect is or for how long it lasts.

However, the makers of Ritalin say that long-term studies of children taking the drug have shown no long-term health problems.

Manufactured by Novartis Pharmaceuticals Corp., Ritalin is the most commonly prescribed medication for attention deficit hyperactivity disorder, which affects an estimated 2 million American children. Children with the disorder have problems sitting still, planning ahead or finishing tasks. The disorder is two to three times more common in boys than in girls.

Senior researcher Joan Baizer, an associate professor of physiology and biophysics at the State University of New York at Buffalo, says the idea for the study began during a discussion about the effects of amphetamines and cocaine on an area of the brain known as the striatum. The two drugs appeared to switch on "immediate early genes," which trigger changes in brain cell function.

Specifically, this involves a gene called c-fos, which seems to be involved in learning and structural and functional changes in the brain.

Baizer, whose daughter takes Ritalin for the hyperactivity disorder, wondered whether the drug might have the same effect.

The full consequences of immediate early gene activation are not fully understood, she says. "You are turning on a gene in brain cells, which is known to then change other genes, which means that the cell is going to be in a somewhat different state than it was before," she says.

To study the effect this might have, the researchers fed sweetened milk containing Ritalin to one group of rats and sweetened milk only to a second group. After 90 minutes, the researchers examined the brains of the animals.

The researchers noticed much more neuron activity involving c-fos in the rats that received Ritalin than in those that got sweetened milk only. Baizer says this is the first evidence of Ritalin's effects on this particular gene.

"We saw a lot of cells that were making this protein, c-fos, in the striatum and in the cortex," she says. "The same thing had been seen with amphetamine and cocaine in similar parts of the brain."

The dose that the researchers fed the rats would be equivalent to a very high dose in humans, but Baizer says this was necessary because rats metabolize Ritalin faster than people. "It would still be a high dose, but it may not be too far out of the therapeutic range," she says.

"It's assumed that you give [Ritalin] to the kid and it's effective for three hours," says Baizer, adding that if could last longer if the child is taking the sustained-release formula. "The next day, you give the same dose, and it's assumed that the brain is back to the same state as it was previously. This would suggest that that's maybe not the case."

"It seems to be changing cell function in a way that's going to outlast the three, four or five hours of immediate clinical effects," she says. A report on the research was presented yesterday in San Diego at a meeting of the Society for Neuroscience.

In a statement issued in response to the study, Novartis stresses that the dose used on the rats makes it difficult to apply the findings to people.

"It is important to recognize that the data being presented…are the results of a single study using a very high dose of methylphenidate in rats," the statement says. "Therefore, this cannot provide any significant insight into effects of methylphenidate as it is administered in the treatment of ADHD."

Moreover, the drug maker says, observational studies of young adults who were treated with Ritalin as children, and of children taking Ritalin who were followed for two to nine years, found no negative, long-term side effects.

So far, the researchers have examined only the effect of a single dose of Ritalin. In the future, Baizer says, they want to examine the effects of repeated treatments and whether other genes also are affected.

But Baizer stresses that the findings, although interesting, are preliminary and should not change how Ritalin is prescribed.

"It's clinically documented over and over again to be an extremely effective and beneficial drug for kids with attention deficit disorder," she says.

What To Do

For information on Ritalin, visit the Internet Mental Health or the National Institute on Drug Abuse Web sites. Or, check out Novartis online.

To learn more about attention deficit hyperactivity disorder, visit the National Institute of Mental Health online or go to the KidsHealth Web site.

SOURCES: Interview with Joan S. Baizer, Ph.D., associate professor, Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, N.Y.; statement from Novartis Pharmaceuticals Corporation United States, East Hanover, N.J.
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