Surging Off-Label Use of Schizophrenia Drugs by Teens and Elderly

(March 9, 2007) -- Teenagers and the elderly in the U.S. are increasingly being given a class of anti-psychotic drugs for uses not cleared by regulators.

Prescriptions for off-label, or unapproved, applications of the medicines are helping to propel sales for AstraZeneca Plc, Johnson & Johnson and Bristol-Myers Squibb Co., market research data show. The practice has caught the attention of Representative Henry Waxman, a California Democrat, who is probing whether drugmakers promote unapproved usage.

The treatments, including AstraZeneca's Seroquel and Eli Lilly & Co.'s Zyprexa, generated $14.7 billion in sales in 2006, 20 percent more than the previous year, based on data compiled by Bloomberg. Doctors are prescribing the drugs to patients with Alzheimer's disease and adolescents with mental-health illnesses, though there is little evidence the pills are safe and effective for these ills, some researchers say.

``The off-label uses have driven a lot of growth,'' said Kate Hohenberg, an analyst with market research firm Decision Resources Inc. in Waltham, Massachusetts. ``Physicians who treat these diseases are desperately looking for something.''

It's legal for doctors to administer drugs for unapproved medical conditions. Companies aren't allowed to market products to doctors for uses not yet cleared by the U.S. Food and Drug Administration in Washington or by regulators in other countries.

`Across the Class'

The drugs, including Johnson & Johnson's Risperdal, Pfizer Inc.'s Geodon and Bristol-Myers's Abilify, were developed to treat schizophrenia, a disorder characterized by hallucinations that affects 24 million people worldwide, according to the World Health Organization in Geneva. The pills also are gaining wider use for adolescents with depression, autism and hyperactivity, dementia in the aged and even insomnia.

Almost half of Seroquel sales in 2006 were for disorders for which AstraZeneca has yet to gain regulatory approval, according to Datamonitor Plc, a London-based market research firm. The other half was for approved indications such as treating schizophrenia and for bi-polar disorder, also known as manic depression, according to Terence McManus, a Datamonitor analyst.

The amount of off-label use is ``across the class,'' McManus said in an interview March 6.

Seroquel sales increased 24 percent in 2006 to $3.4 billion. Revenue may jump 30 percent more this year to $4.4 billion, according to David Seemungal, an analyst at Standard & Poor's Equity in London. He estimates that Seroquel sales of London- based AstraZeneca will peak in 2010 at $5.75 billion.

`Policies in Place'

``We have policies in place that provide direction around the appropriate promotion of our product,'' said Jim Minnick, an AstraZeneca spokesman. Lilly's spokeswoman Carole Puls said the drugmaker doesn't promote off-label use.

Johnson & Johnson spokesman Srikant Ramaswami declined to comment on why off-label use is increasing. ``We promote our products only for their FDA-approved indications, and we support scientific and clinical studies that advance what is known about our products,'' he said.

The drugs, known as atypical anti-psychotics, appear to work by interacting with several brain chemicals that help carry signals among nerve cells. The drugs made up one of the top- selling classes of medicines last year behind the $20 billion from cholesterol-lowering statins such as Pfizer's Lipitor.

Delusions, Hallucinations

Twenty-five to 35 percent of patients in nursing homes who are diagnosed with dementia received an antipsychotic drug such as Zyprexa last year, Hohenberg of Decision Resources said. The figures are based on physician surveys and prescription trends, she said.

The use of these drugs in the elderly to quell the delusions, aggression and hallucinations of Alzheimer's disease is a concern, some doctors say. An analysis of 17 studies involving 5,000 patients found that elderly people with dementia- related behavior problems who took the drugs had a death rate almost two times higher than those who didn't take the medicines, according to an FDA public health advisory issued in April, 2005.

The research led the FDA to require the drugmakers place a prominent notice surrounded by a black box on the products' descriptive label for doctors, warning of the increased risk of death from heart disease and pneumonia in the elderly.

States File Suit

``There is a perception that these drugs are safer, so there is less reservation about using them,'' said Jeffrey Lieberman, head of psychiatry at Columbia University in New York. ``Is this increased use warranted? That we don't know yet.''

Lieberman led a study published in October, 2006 involving 421 patients that found the drugs side effects when used in the elderly outweighed benefits.

AstraZeneca's Seroquel was the only drug in the class to have an increase in sales to elderly patients with dementia after the warning was issued, while the other drugs' use in the aged declined or was unchanged last year, Hohenberg said.

Indianapolis-based Lilly has been sued by six states -- Louisiana, West Virginia, Alaska, Mississippi, New Mexico and Pennsylvania -- on behalf of Medicaid programs, seeking reimbursement of money spent on Zyprexa. Louisiana has also sued Johns & Johnson over Risperdal, and last week Pennsylvania filed suit against Lilly, AstraZeneca and Johnson & Johnson over these drugs.

All the suits allege that the drugmakers failed to disclose the risks of side effects caused by the drug and promoted their use to treat conditions for which they were not approved.

Targeting Elderly

``They were convincing primary-care physicians that this medication is so safe and so good, you can prescribe this to single moms who are anxious,'' said Mark Burton, an attorney at Hersh & Hersh in San Francisco, who represents New Mexico in a suit against Lilly. The company also targeted ``elderly people and people who were on public assistance. The states have been spending tens of millions of dollars on the drug.''

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AstraZeneca spokesman Minnick said the company will ``vigorously defend'' itself against the lawsuit. Johnson & Johnson's Ramaswami said the suits are ``without merit.'' and Lilly declined to comment.

Bloomberg News filed a freedom of information lawsuit against the FDA in November, 2006 asking for public access to documents related to off-label uses of the drugs. The matter is under judicial review.

To contact the reporters on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net ; Etain Lavelle in London at at elavelle1@bloomberg.net .

By: Shannon Pettypiece and Etain Lavelle
Source: Bloomberg

Last updated: 03/07

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