http://www.abc.net.au/science/news/health/HealthRepublish_414363.htm
New calls for long-term Ritalin study
Monday, 12 November 2001
New evidence about the effects of Ritalin, a drug used to treat children with
ADD and ADHD, has prompted renewed calls for research into its long-term
effects.
Dr Joan Baizer and colleagues from the University at Buffalo, State University
of New York have found that relatively high doses of the drug methylphenidate,
the generic form of Ritalin, changed the expression of a gene involved in brain
function in laboratory rats. The same gene is known to be affected in humans by
other psychoactive drugs, such as amphetamines and cocaine.
The researchers presented their findings this week at the annual meeting of the
US Society for Neuroscience.
"Children have been given Ritalin daily for many years, and it is extremely
effective and beneficial, but it's not quite as simple as a short-acting drug,"
said Dr Baizer.
"[It] does appear to be safe when used properly, but it is still important to
ask what it is doing in the brain."
Dr Bazier and team noted that previous studies had shown high doses of
amphetamines and cocaine changed certain aspects of brain cell function.
Ritalin, like these drugs, is a stimulant, so they decided to test whether it
might have similar effects.
Young rats were used in the experiment. One group was given sweetened milk
containing Ritalin, and their brains were compared to those of another group
given just sweetened milk.
According to Dr Baizer, the dose used was comparable to the high end of the
dose used to treat children with ADD and ADHD, after taking into account
differences in metabolism between rats and humans.
The researchers found Ritalin increased the activity of a gene called c-fos in
the striatum, a part of the brain involved in movement and motivation.
"These data do suggest that there are effects of Ritalin on cell function that
outlast the short term and we should sort that out," Dr Baizer said.
ADHD researcher Dr Alasdair Vance of Melbourne's Alfred Hospital said the study
demonstrated the importance of studying the long-term effects of Ritalin.
"These drugs may have considerable benefits for children and families at large,
but the key issue is that our understanding of these medications — and
therefore their appropriate and optimal use — must be made a priority," he
said.
"I am concerned about the long-term use of these drugs, given their exponential
increase in use in the community on a very insubstantial scientific base."
According to Dr Vance, children with ADHD (attention deficit hyperactivity
disorder) and ADD (attention deficit disorder) are believed to have a problem
in the parts of the brain that integrate information from different senses.
These children lack the motivation for picking up what's important, and can't
seem to block out what's not important. Ritalin is believed to work by
increasing the amount of the nerve transmitter dopamine in these parts of the
brain.
"While this generally benefits children with ADHD and ADD in the short term, in
the long term, such reorganisation may eventually mean the drug stops working,
or even makes the problem worse," said Dr Vance.
In some children the beneficial effects of Ritalin appeared to decline despite
continued medication, he said, adding that there is an enormous need to study
the long-term effects of Ritalin on the brains of primary school-aged children.
"Yes, there are studies that show Ritalin is effective," he said. "But they
only look at single doses, or what happens in the first three to six weeks. The
vast majority of children are on it for months to years."
The handful of longer-term studies of Ritalin use had only looked at symptoms,
not brain physiology, he cautioned.
"We must now look at the long-term effects using juvenile animal models and
longitudinal studies in children."
Dr Vance praised the US researchers' decision to use juvenile rats, which he
said were more relevant to the developing brains of young children.
"It's not that these drugs are bad, it's just that we don't know how best to
use them, and we need to move away from simplistic models that do not take into
account the developmental context of the child."