Preschool Meds

By SHERYL GAY STOLBERG

n a warm, breezy Friday in September, a parade of mothers in minivans arrived at a preschool in suburban Connecticut to drop off a collection of 4-year-olds. Among the young students was Sam G., a sturdy, big-eared boy with cheeks that flush easily and a personality that has earned him a reputation, politely speaking, as a handful.

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Like most 4-year-old boys, Sam loves things that move -- trains, planes and trucks, especially fire trucks -- and is usually on the move himself. When he enters a room, his clear blue eyes dart about, as though he cannot take in the sights fast enough. His knees and elbows are perpetually scraped. When his teachers read stories aloud, Sam often wanders about.

This particular Friday was no exception. It was Bring-Your-Stuffed-Animal-to-School Day, and Sam burst through the door carrying a two-foot-tall black-and-white cow he calls Moo. Surveying the scene, he paused momentarily and then, as if someone had lighted a fuse underneath him, thrust his arms forward and began zipping around the room, the cow acting as his shield. During the next two hours, Sam tried to open the childproof window locks; he got into fights in the sandbox and repeatedly stood in the center of the room, swinging the cow by its tail. When his teacher finally put the animal on the shelf ''for a nap,'' Sam burst into tears.

Time was, Sam's rambunctiousness would have been chalked up to childhood or, more precisely, boyhood. Today, Sam has a diagnosis -- attention deficit hyperactivity disorder, and a potential treatment: methylphenidate, a drug better known by its brand name, Ritalin. Sam has been taking the drug, in various doses that are interspersed with dummy pills, since July as part of the three-year Preschool A.D.H.D. Treatment Study, known as PATS. This unusual clinical trial is financed by the National Institute of Mental Health and overseen by the New York State Psychiatric Institute in Manhattan. The institute, which is affiliated with Columbia Presbyterian Medical Center, is one of six academic medical centers around the country that have been recruiting children since January 2001. The aim is to enroll 314 children by February. Results are expected sometime in 2004.

The research may be the most controversial medical experiment the federal government has ever conducted in children: a study of the safety and effectiveness of generic Ritalin in preschoolers, ages 3 to 5. Experimenting on children is always delicate, especially when the children are barely out of diapers. Ritalin, marketed to help hyperactive students focus in school, is a stimulant, and though it is generally considered safe, scientists acknowledge they do not understand how it affects young children's developing brains. The drug is not approved for children under age 6. But doctors increasingly prescribe it to them ''off label'' -- a worrisome trend, yet hardly surprising in an era when 3-year-olds are expected to know their numbers and 5-year-olds are being taught to read.

''We have an obsession with performance in our country,'' says Lawrence Diller, a behavioral pediatrician in Walnut Creek, Calif., and the author of two books on A.D.H.D. ''We have a universal performance enhancer in Ritalin. It helps anyone, child or adult, A.D.H.D. or not, to perform better. It was inevitable that there would be this drift down to the 3- to 5-year-old set.''

Darlene and Brian G., who insisted that their last names not be used to protect Sam's privacy, had struggled for years to have a child. Darlene, a compact 51-year-old woman with blond hair and jade-green eyes, was 39 when she married Brian, an engineer 13 years younger than she is. In 1997, having exhausted their emotional and financial resources on in vitro fertilization, they decided to adopt.

Sam was born Dec. 18 of that year to a 17-year-old. Only later would the couple learn that their son's biological mother, as well as some of her relatives, had been given the diagnosis of attention deficit hyperactivity disorder.

By the time Sam started walking, two things about him were clear: he was fearless and always on the go. When he was 2, Sam climbed onto the dining-room table and tried to swing from the ceiling fan. He switched on the electric stove, then stretched his little body across the burners. He tripped the latch on a sliding-glass door, then let himself out on the second-story balcony. Darlene yanked him back as he was about to topple over the rail.

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Brian thought Sam was just being a boy, and the pediatrician seemed to concur. When Darlene asked about testing for hyperactivity, he told her to wait until Sam was 5 or 6, and in school. ''If I live that long,'' she shot back.

When Sam was 3, the director of his preschool called to say that Sam had raised his fists to her ''and we can't have that kind of behavior here.'' Darlene, upset yet relieved that someone else had seen what she saw, called Brian in tears. ''He's going to get kicked out of preschool,'' she told him. ''He's only 3!''

A local psychologist diagnosed A.D.H.D. in Sam and recommended therapy. Darlene, a believer in holistic medicine, also took Sam to a naturopath, who tested him for food sensitivities and severely restricted his diet: no wheat, dairy, gluten, corn syrup or food additives. The entire family gave up pizza. At school birthday parties, Sam got soy ice cream.

By the time Sam turned 4, the family's insurance coverage for the therapy was running out. Then Darlene's cousin alerted her to an advertisement in The New York Daily News. ''Is your preschooler just too active?'' the ad asked. It promised ''a comprehensive evaluation by our study team, as well as up to 14 months of treatment -- all at no cost.''

he man behind the advertisement was Laurence L. Greenhill, a 61-year-old child psychiatrist at the Psychiatric Institute on Riverside Drive in New York City. Square-shouldered and stocky, with wire-rimmed glasses and dark wavy hair that he slicks down for speaking engagements, Greenhill is what pharmaceutical companies call a K.O.L. -- key opinion leader -- which means he conducts the cutting-edge drug research that shapes prescribing decisions for thousands of ordinary doctors who treat A.D.H.D. He is serious almost to the point of being humorless, a trait that colleagues say serves him well.

''Among people who do work like this, studies on the very young, the very sick, there is no shortage of cowboys,'' says Steven Hyman, who was the director of the National Institute of Mental Health at the N.I.H., when the study was approved. ''Larry Greenhill is not a cowboy.''

Greenhill came of age in psychiatry at a time when medical experts were beginning to regard hyperactivity as not simply a behavioral disorder but a condition with a biological basis, akin to asthma or diabetes, that could be corrected with medicine. In 1998, having already helped lead a landmark study of Ritalin in school-age children, he turned his attention to preschoolers. In November 1999, the National Institute of Mental Health agreed to finance his preschool study.

But before the money was released, a scientific landmine exploded in the middle of the long-running Ritalin debate. In February 2000, The Journal of the American Medical Association reported a twofold-to-threefold increase in the use of stimulant drugs, particularly methylphenidate, among 2- to 4-year-olds. The study, by Julie Magno Zito, a pharmacy professor at the University of Maryland, did not shock doctors who treat A.D.H.D. But it did shock the public.

''Those of us who have been prescribing medication since the 70's had been watching this huge increase,'' Lawrence Diller says. ''Zito's piece put it on the front page of every newspaper.''

Hillary Clinton, still first lady but running for Senate in New York, demanded to know what the government was doing about it. Hyman told her about Greenhill. Within weeks, the White House had announced a major initiative to reduce the use of stimulants among the very young. The preschool study was a central component.

Critics argue that the trial may, in fact, increase stimulant use, legitimizing it for children who are not as closely monitored as Sam. But Hyman defends his decision to go ahead, given that so many preschoolers are already on the drug. ''If we can do these trials right,'' he says, ''we are damnable if we don't do them. Because if we don't do them, then every child becomes an uncontrolled experiment of one.''

To Peter Breggin, the nation's best-known A.D.H.D. critic, the study marked ''a tragedy for America's children.'' A soft-spoken, silver-haired psychiatrist, Breggin is the author of more than a dozen books, including ''Talking Back to Ritalin.'' With his gentle manner and frequent television appearances, Breggin puts forth an appealing -- and, Greenhill contends, troubling -- message: attention deficit hyperactivity disorder is a figment of modern psychiatry's imagination.

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Flipping through the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders on a recent afternoon, Breggin read aloud from its list of A.D.H.D. symptoms: ''Often fails to give close attention to details or makes careless mistakes in schoolwork. Often fidgets with hands or feet or squirms in seat. Often blurts out answers before questions have been completed.'' He scowled.

''There is no disease,'' he said flatly. ''It's a list of behaviors that annoy adults.''

On Jan. 23, 2002, Sam and his parents made the first of what would become weekly visits to the psychiatric institute. They had come to meet Dr. Janet Fairbanks, the child psychiatrist and colleague of Greenhill's who would evaluate Sam.

Diagnosing A.D.H.D. is difficult with any child, but with preschoolers, who tend to be active and impulsive, it is especially hard. The medical literature suggests A.D.H.D. is often overdiagnosed and overtreated, which is one reason Breggin's arguments have gained so much currency.

Contrary to the perception that Ritalin is being used as a kind of ''chemical handcuff'' for inner-city kids, studies show the drug is most often prescribed to white suburban boys -- in short, kids like Sam. Sensitive to the controversy, the mental-health institute insisted that Greenhill's team require parenting training: 10 weeks of classroom instruction in behavior modification. Children who show little or no improvement at the end of the 10 weeks then become eligible for medication.

The team also set strict limits on who can enroll, taking only the most severely affected children. Fairbanks knew right away Sam would qualify. The electric stove story, she says, was a big tip-off. ''He has no sense of danger, which is characteristic of these kids, which is why they get hurt a lot. It's curiosity, combined with no impulse control.''

By April, the psychiatric institute had recruited enough children, 13 in all, including a set of 3-year-old twins, to begin its next round of parent training. The course was led by Tova Ferro, a clinical psychologist who herself was expecting a child. On the night I sat in, the lesson was timeouts. Ferro popped a video into a recorder, and a man appeared on the television screen, begging his toddler to put away her toys amid lame threats of a timeout. Ferro asked what the father had done wrong. ''He was a wimp,'' one mother piped up. Ferro agreed. She advised the parents to make a list of behaviors serious enough to warrant a timeout. Every family is different, she told them. ''Think about what makes sense for you.''

Although her goal is to help parents improve their children's behavior, Ferro is under no illusions. ''Some children will need additional interventions,'' she said. Translation: Some will need drugs.

For Brian and Darlene, the parent training was mostly a review of what they had already picked up in parenting books, though they enjoyed the emotional support. But as with every other aspect of the PATS clinical trial, the parent training, modeled on a Canadian program, has critics. Among them is William E. Pelham Jr., director of the Center for Children and Families at the State University of New York at Buffalo.

At his center, Pelham offers intensive training for teachers and summer camp for hyperactive kids -- programs that he says help as many as 75 percent avoid medication. He says that Greenhill's less intensive training is set up to fail.

''I bet you 100,000 bucks I could tell you the results of that trial,'' Pelham said. ''The results will be that kids need medication because parent training is not enough. I think that's dangerous. It is going to send a message to people that young children need medication.''

But the cold truth, says Hyman, the former director of the mental-health institute, is that few Americans could afford the kind of help Pelham offers. ''We were very concerned,'' he said, ''that any behavioral therapy that came out of this trial had to be generalizable.''

In Sam's case, the training was of little help, and the question of whether to put him on medication was much on his parents' minds throughout the 10-week session. On Sam's good days, Darlene was convinced she should hold out until he started school. On bad days, she was ready to cave. In the end, it was Brian who made the decision.

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He liked the idea that Sam would be carefully monitored, that his medication would be increased only gradually until doctors determined the optimal dose, which he would take for 10 months. The father who once insisted his son was just being a boy had come to accept him as a boy with a problem.

''My eyes,'' Brian said, ''have been opened.''

Sam started the medicine on the first Saturday in July. The following Friday, he strutted into the institute wearing one of his many fire truck shirts. His mother was glowing. ''Today,'' Darlene announced, ''was wonderful.''

In keeping with the study requirements, Fairbanks started Sam on an extremely low dose, 1.25 milligrams of methylphenidate, once a day. Every two days, the dose went up; by Thursday, Sam was on 7.5 milligrams once a day, still much less than the study's maximum dose of 7.5 milligrams three times a day. Darlene had given him the medicine, a tiny white pill, in a bowl of applesauce at 10 a.m. At 10:45, she ran a little experiment. She offered Sam a spray bottle of pet deodorizer and asked him to help her spray the couch.

To his mother's astonishment, Sam did not run around the house squirting everything in sight. He stood in front of the couch and sprayed the cushions. Later, on a trip to the drug store, Sam asked if he could get a toy. When Darlene told him he would have to wait, he said, ''O.K., Mom.'' She nearly burst into tears.

By 2 p.m., the magic was over. The medicine was wearing off. In the car on the way to their appointment, Sam was looking at a newspaper when Darlene heard the sound of paper crumpling. She asked Sam not to tear the paper, but he couldn't stop. Soon, his whole body was in motion, feet jangling, fingers wiggling.

That Friday, in Fairbanks's cramped office, the family squished next to one another on the psychiatrist's couch, all of Darlene and Brian's hopes and fears came spilling forth. They wondered aloud how they might channel Sam's impulsiveness and lack of fear. He could be an explorer, Darlene suggested. An astronaut, Fairbanks chimed in. ''I want him to be a leader,'' Brian said finally. ''I want him to follow his dreams.''

Later, they took Sam out for pizza in the city, a rare treat. ''I am starting to go on Ritalin,'' he announced. ''They're these little tiny pills. They're for to help me.'' Help you with what? I asked. ''To help me with helping,'' he replied, as if this were the most obvious thing in the world. ''With helping and listening.''

Then a bus rumbled by on Broadway, and Sam turned to look. Soon, he was out of his seat, darting for the door, his father calling out after him. It would be another 15 hours before his next little white pill.

It was a difficult summer -- ''a roller coaster,'' in Brian's words. The trial followed a complicated double-blind crossover pattern, with the doses, and hence Sam's behavior, changing week to week. While outside experts charted Sam's responses, Sam's parents and doctors were kept in the dark. Darlene, though, wasn't fooled. The week Sam played Boggle Jr., a spelling game, for 30 minutes, was a high-dose week. The week he opened the childproof bottle of Clorox and accidentally doused himself in bleach (''I wanted to help you with the laundry,'' he told Darlene) was the placebo week.

By September, things had grown even more complicated. During a high-dose week, Sam developed a tic -- a common and disconcerting side effect. It began subtly, an odd, occasional rolling of the shoulder, as though Sam were trying to wriggle out of his shirt. It didn't bother him, or his parents, until a few days after Labor Day, during a family trip to Cape Cod.

They were eating lunch when Darlene spotted Sam's arms going, first his left, then his right. His eyes grew big; his expression went blank. When she asked Sam to squeeze her hand, he couldn't; his own hand was curled up in a feeble knot. For two hours, Darlene and Brian watched their son deteriorate until, just as suddenly as it began, the twitching subsided. Frightened, they temporarily stopped the medication.

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These kinds of reactions, Greenhill says, are just what his team is looking for, although the cause of Sam's tic remains unclear. It could be a side effect that goes away when the child stops taking the drug. Or Sam may have a tic disorder, which sometimes occurs alongside A.D.H.D. And there is also another, more troubling possibility, Fairbanks says: ''Does the medicine somehow release something that was a vulnerability? And will it continue after the medication is stopped?''

The tic prompted Fairbanks to ask Sam's parents if they wanted to withdraw him from the trial. But Darlene and Brian, who once worried so much about putting their son on medication, did not want to take him off. ''It's too soon to give up,'' Brian said. Today, Sam takes his optimal -- and much lower -- dose. The occasional shoulder roll remains.

Fairbanks has seen this kind of determination before. The parents of two of her patients were crushed when their children had to leave the trial because of appetite loss and insomnia, side effects of the medication.

In his own way, Sam seems to sense his parents' dilemma. On the drive back to Connecticut after a recent visit with Dr. Fairbanks, he pointed out the George Washington Bridge and talked about the pumpkin garden he had planted. Then he declared that he had become a parent.

''I have a child,'' he said, in his serious, earnest way. ''His name is Billy. He just turned 3. He knows all his alphabets. He knows at school when recess time is on. He knows when the bell rings, and they're going out. He listens to his teachers. He cleans up when he's supposed to.''

It did not take a child psychiatrist to figure out that, in his imagination, Sam had neatly created the boy he hopes to be.