Sept. 4 (Bloomberg) -- The number of American children diagnosed with bipolar disorder, a mental illness, jumped 40- fold from 1994 to 2003, according to a study in the Archives of General Psychiatry.

By 2003, the diagnosis was applied to 1 in 100 kids, researchers found. Of the 800,000 people ages 19 and younger with the diagnosis, nine in 10 were treated with at least one drug and two-thirds with two or more, according to the study, reported yesterday. Adult diagnoses almost doubled to 1,069 for each 100,000 people, and the rate among kids reached 1,003.

Researchers said they didn't know if the rise in children was caused by underdiagnosis in the past or too much now. That question is sparking new debate as companies such as Eli Lilly & Co. and Bristol-Myers Squibb Co. seek U.S. clearance to sell drugs tied to side affects including weight gain and diabetes.

``There's no question that there is misdiagnosis going on,'' said Gary Sachs, director of the bipolar and mood disorders program at Massachusetts General Hospital in Boston, who was not involved with the study. ``You can dispute whether it's under- or overdiagnosis.''

The study was drawn from an annual government survey of doctors. The expanded use of bipolar as a pediatric diagnosis has made children the fastest-growing part of the $11.5 billion U.S. market for antipsychotic drugs. J&J won U.S. clearance Aug. 22 to market Risperdal for use in children ages 10 and older.

Drug Stocks

Indianapolis-based Eli Lilly & Co. and New York-based Bristol-Myers Squibb Co. are seeking similar approval to market competing antipsychotic drugs for use by children.

Bristol-Myers gained 7 cents to $29.22 at 4:00 p.m. in New York Stock Exchange composite trading. Johnson & Johnson gained 19 cents to $61.98. Pfizer Inc., producer of the bipolar drug Geodon, gained 24 cents to $25.08. Lilly rose 78 cents to $58.13. In London, AstraZeneca Plc, the maker of the antipsychotic Seroquel, increased 34 pence to 2,466.

Bipolar disorder was once known as manic depression. In classic, adult versions of the disease, people stay lodged for weeks or months in states of deep depression, then shift to a manic phase in which they sleep little, have intense energy, talk rapidly, and may engage in risky behavior.

Starting in the mid-1990s, some psychiatrists began to argue that the disorder looks different in children, who may alternate more rapidly between depression and mania. In their view, the key sign of a bipolar child is a high level of irritability and rage. The disorder has been linked to poor school performance and substance abuse.

A third to half of patients referred to the Massachusetts General clinic with a diagnosis of bipolar turn out not to have a confirmable case, Sachs said. Patients treated for a diagnosis they don't have won't respond to the treatment and end up getting a lot of different medications, he said.

`More Side Effects'

``They're likely to get more side effects than benefit,'' he said.

Sachs says his ``personal belief is that the true rates of bipolar disorder'' in children may be as much as twice the number estimated by the paper. Despite the side effects, the medications can be effective in treating patients who truly have bipolar disorder, Sachs says.

Treating kids is ``the compassionate thing to do when you see a child suffering, or out of control,'' he said.

When children are misdiagnosed, the result can be dangerous, said Mark Olfson, a psychiatrist at Columbia University in New York who led the study. Several factors make him question the reliability of many bipolar diagnoses, he said.

The disorder in adults is seen mostly in women, yet about two-thirds of diagnosed children are boys. Many children said to have bipolar were also diagnosed with attention deficit disorder, a condition that can look similar, Olfson said.

`Serious Consequences'

``If we're getting this wrong, if substantial numbers of kids are being misdiagnosed with bipolar disorder, it can have serious consequences,'' Olfson said in an Aug. 31 telephone interview.

Two groups of medications are widely used to treat bipolar disorder in children.

Anticonvulsants, developed to treat epileptic seizures, were taken by about half of the children. Drugs in this group include Depakote made by Abbott Laboratories; Johnson & Johnson's Topomax; GlaxoSmithKline Plc's Lamictal; Novartis AG's Tegretol and Pfizer Inc.'s Lyrica and Neurontin.

None are approved by U.S. regulators for treating children with bipolar disorder. Side effects include sedation, weight gain, tremor, and, more rarely, liver and blood problems.

Antipsychotics

Almost half the children took atypical antipsychotics, such as Lilly's Zyprexa, J&J's Risperdal, AstraZeneca Plc's Seroquel, Bristol-Myers' Abilify and Pfizer's Geodon. Side effects linked to this group of medications include weight gain, diabetes and hormonal irregularities.

Risperdal, J&J's top-seller, generated $4.2 billion last year while Zyprexa had $4.4 billion in sales. The FDA is reviewing Zyprexa and Bristol's Abilify for teens.

Lilly is also developing an experimental antipsychotic drug that didn't show the same side effects in the second stage of testing normally required for regulatory clearance, the company said yesterday. That drug targets a different brain chemical than drugs now on the market.

Vivek Kusumakar, global head of Risperdal development for J&J, said when it was approved that the side effects must be weighed against the potentially fatal conditions it treats.

David Healy, a professor of psychological medicine at Cardiff University in Wales, said the rise in the diagnosis was unprecedented. Healy, who has served as an expert witness for lawyers suing drug companies, said he was particularly concerned that so many children were prescribed more than one drug.

``The mismatch between possible benefits and likely harms is great,'' he said.

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net.

Last Updated: September 4, 2007 16:18 EDT