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Impulsive, hyperactive, easily distracted, impatient. For many parents, this description could be applied to any young child still learning acceptable social behavior. But for millions of children in the U.S., something in their brain chemistry causes these traits to persist at exaggerated levels and negatively affects their learning and relationships.

Attention deficit hyperactivity disorder (ADHD), the diagnosis applied to such children, has been a condition fraught with controversy since it was first recognized by the medical community. And nothing has ignited the passion of doctors, parents, and patients like the use of stimulant drugs such as Ritalin as treatments.

According to the National Institute of Mental Health, the disorder that would eventually be dubbed ADHD first gained serious attention in 1902. That year, English pediatrician Sir George F. Still published a series of lectures describing children with significant behavioral problems that could not be attributed to the way they were raised. He proposed their behavior was instead caused by a neurological disorder. Since then, numerous studies have been conducted to define the disorder and identify the best treatments.

Doctors in the 1950s named the condition minimal brain dysfunction based on the idea that affected children suffered from externally induced brain damage. Subsequent research proved the situation was more complex, and doctors assigned new titles to the disorder, eventually settling on ADHD in the 1980s. But even as its definition evolved, the major ADHD treatments remained based on a single type of drug: amphetamines.

"ADHD has been treated with amphetamines since 1937," says Paul H. Wender, a distinguished professor emeritus of psychiatry at the University of Utah School of Medicine known as the "Dean of ADHD" by his colleagues. Amphetamines, powerful central nervous system stimulants, had a paradoxical effect on hyperactive patients, helping them to calm down and focus on tasks.

"All stimulants work the same in terms of the mechanism of action," says Susan L. Andersen, director of the developmental psychopharmacology laboratory at McLean Hospital, Belmont, Mass. The drugs affect the release and reuptake of the neurotransmitters dopamine and norepinephrine. Where healthy people would experience euphoric highs from taking stimulants, low doses given to ADHD patients have a calming effect.

In 1955, the Food & Drug Administration approved methylphenidate, an amphetamine derivative developed by Ciba-Geigy, for a variety of psychological disorders. But it wasn't until several years after the compound's patent expired in 1967 that Ritalin--Ciba's brand-name version of the drug--was indicated to treat ADHD in children.

Ritalin was originally sold as 5-, 10-, and 20-mg tablets to be administered three times a day. Today, Ritalin also exists as a sustained-release 20-mg tablet and a long-acting 20-, 30-, or 40-mg tablet.

"In the 1970s, when Ritalin was introduced, Ciba sponsored a great deal of research" on ADHD medication, Wender says, putting its brand name first in the public eye. By 1975, more than 1 million U.S. children had been diagnosed with ADHD. Of the half-million patients being treated with drugs, approximately 265,000 were prescribed Ritalin.

In the mid-1990s, ADHD diagnoses nearly doubled to 2 million, prompting public fears of misdiagnosis and overmedication. Ritalin fast went from a brand name to a punch line as advocacy groups began to question ADHD's validity as a disease and charged drugmakers with pushing unnecessary medications.

"ADHD likely has more subtypes than we are aware of due to problems assessing it," Andersen says. Symptoms of ADHD can appear in conjunction with other developmental disorders, and ADHD-like behavior can also be a temporary response to trauma.

THE MOST RECENT edition of the "Diagnostic and Statistical Manual of Mental Disorders," published by the American Psychiatric Association, offers criteria for diagnosing ADHD that require extensive evaluation of a patient's medical, psychological, educational, and social behaviors.

Even with a positive diagnosis, individuals respond differently to the available medications, so doctors must adopt a trial-and-error approach in deciding what and how much to prescribe.

"Amphetamine and methylphenidate are equally effective," Wender says, "but some people respond better to one than the other." Efficacy studies on methylphenidate indicate that about 70% of participants show improvement, while 30% have unchanged or worsened symptoms and must seek alternative treatments.

Despite the uncertainties, most doctors believe that stimulant drugs are making a difference for ADHD patients. "Methylphenidate and amphetamines play an important role in the treatment of this common disorder," Wender says. "They are still very useful."—VICTORIA GILMAN

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