Under pressure from parents and schools looking to control attention deficit/hyperactivity disorder (ADHD), doctors commonly prescribe methylphenidate (MPH), best known by the brand name Ritalin, as a treatment for children as young as 2 -- even though the drug has been tested and approved only for children ages 6 and up.

A report published early last year in the Journal of the American Medical Association by Julie Zito, an epidemiologist at the University of Maryland School of Medicine in Baltimore, estimates that some 150,000 to 200,000 children between the ages of 2 and 4 in the United States are currently receiving prescriptions for MPH.

Steven Hyman, director of the National Institute of Mental Health (NIMH) in Rockville, asks, "How can we tolerate a situation in which drugs are prescribed to an increasing number of preschoolers without safety and efficacy data?"

Laurence Greenhill, of the New York State Psychiatric Institute at Columbia Presbyterian Medical Center, thinks we can't. Greenhill organized a consortium of six institutions to apply for a grant to study the effects of Ritalin on a group of children ranging in age from 3 to 8. About two-thirds of the 312 children to be enrolled in the \$6 million Preschool ADHD Treatment Study (PATS) will be younger than 6 years old.

Greenhill's plan has raised ethical questions of its own, including whether children this young should be subjected to clinical trials of any drug, much less one with Ritalin's ability to alter the way the brain works. In addition to concerns about possible effects on a young child's developing brain, many question whether little children can adequately understand their participation and articulate their willingness to take part in any clinical trial.

Hyman says all of this has been thoroughly examined and planned for, both by the research team and through the NIMH's and local institutional review processes. "We were tied up in knots by this," he says, acknowledging the vetting to which the NIMH subjected Greenhill's plan.

The study is designed to include children with moderate to serious symptoms who have never been medicated for ADHD. Before any child joins the study, his parents receive training intended to help them improve the child's behavior without drugs. Children who respond positively to these efforts will be dropped from the study. Only those whose symptoms remain moderate to severe will continue. After the correct dose for each child is established, he or she will be monitored for 40 weeks to ascertain the drug's longer-term effects.

"The consent process is active and ongoing," says Greenhill. "Parents are re-consented at each of five stages." Children accepted into the study must be fluent enough to object to what's going on; each will be offered an age-appropriate explanation and will be asked to either assent or say no to further testing.

Psychiatrist Peter Breggin, the Bethesda-based author of the 1998 book "Talking Back to Ritalin," has been one of the most outspoken of the drug's -- and the study's -- detractors.

"We shouldn't be giving addictive drugs to kids because we're not willing to give time to them," says Breggin, who advocates non-pharmaceutical treatments such as parental training for the set of symptoms known as ADHD. "All ADHD is, is a list of symptoms that irritate teachers," Breggin says. "To call it a disease is ridiculous, and to say it's hard to treat is meaningless. What we're doing is drugging our kids instead of improving family life and schools.

"If the NIMH were being responsible, they'd call for a moratorium on drugging little children," Breggin says. "There is no scientific way to rule out that we're ruining their brains."

Greenhill counters: "The naysayers may say this isn't needed, but we have to try to collect information because it's been shown that more and more children in this age group are receiving this medication, and we don't have any idea about safe dose range or how it works over time."

"Of course there are some children who are over-medicated, but also some who are horrendously impaired," adds Hyman. "We worry about the impact of treatment on the developing brain, but also the impact of no treatment on the developing brain."

"Without a controlled trial," Hyman says, "in essence every kid is an uncontrolled experiment -- but we never learn anything."

The trials are due to begin this month at six sites, including Johns Hopkins University in Baltimore.

-- Jennifer Huget