Bipolar Diagnosis in Kids Jumps 40-Fold in 10 Years As Companies look for New Uses for Old Drugs

From this Report

The number of children in the U.S. diagnosed with bipolar disorder, a mental illness once seen mostly in adults, jumped 40-fold between 1994 and 2003, according to a study in the Archives of General Psychiatry.

By 2003, about 1 percent of children were diagnosed, or 1,003 for every 100,000 people age 19 and younger. The adult rate almost doubled to 1,069. Nine in 10 kids diagnosed with the disorder were on at least one drug, and two-thirds took two or more, said researchers led by Mark Olfson, a psychiatrist at Columbia University in New York.

Doctors said they don't know if the rise was caused by too little diagnosis in the past, or too much now as a one-size- fits-all response to aggressive behavior. The question is sparking debate as companies such as Indianapolis-based Eli Lilly & Co. and New York-based Bristol-Myers Squibb Co. seek to market drugs for children linked to 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. [...]

The absolute number of children treated jumped to 800,000 from 20,000 during the 10-year study, according to data gathered from the National Center for Health Statistics survey of office visits by the researchers. The rate jumped from 25 for every 100,000 people age 19 and younger.

Manic Depression

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.

Sachs said that one-third to one-half of patients who have been referred to his clinic with a diagnosis of bipolar turn out not to have a confirmable case. 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.

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

[...]

When children are misdiagnosed, the result can be dangerous, said Olfson, a psychiatrist at Columbia University. He said there are several factors that make him question the reliability of many bipolar diagnoses.

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

``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.

Medication Types

Two groups of medications are widely used 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.

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.

Nearly 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 caused by this group of medications include weight gain, diabetes and hormonal irregularities.

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

Risperdal in Children

Risperdal was cleared for use in children ages 10 and older on Aug. 22, beating Lilly and Bristol-Myers in a push to expand use of such medicines by younger patients. Risperdal, J&J's top- seller, generated $4.2 billion last year while Lilly's Zyprexa had $4.4 billion in sales. The FDA is reviewing Zyprexa and Bristol's Abilify for teens.

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.