Where money, medicine intersect - debate

Psychiatrists scrutinized for ties to drug makers, the drugs they prescribe

BY GARDINER HARRIS, BENEDICT CAREY and JANET ROBERTS
New York Times

TwinCities.com-Pioneer Press
Article Last Updated:05/09/2007 11:47:53 PM CDT

When 12-year-old Anya Bailey developed an eating disorder, her mother took her to a psychiatrist at the University of Minnesota who prescribed an antipsychotic drug called Risperdal.

Created for schizophrenia, Risperdal is not approved for eating disorders, but increased appetite is a side effect, and doctors may prescribe drugs as they see fit. Anya gained weight but within two years developed a crippling knot in her back. She now receives regular injections of Botox to unclench her painful back muscles.

Isabella Bailey, her mother, said she had no idea children may be especially susceptible to Risperdal's side effects. Nor did she know Risperdal and similar medicines were not approved at the time to treat children.

Surprising, too, Bailey said, was the U psychiatrist who supervised Anya's care received more than $7,000 from 2003 to 2004 from Johnson Johnson, Risperdal's maker, in return for lectures about one of its drugs.

Doctors, including Anya Bailey's, say payments from drug companies do not influence what they prescribe for patients. But the intersection of money and medicine, and its effect on patients, has become a contentious issues. Nowhere is that more true than in psychiatry, where increasing payments to doctors have coincided with the growing use in children of a relatively new class of drugs known as atypical antipsychotics.

These best-selling drugs, including Risperdal, Seroquel, Zyprexa, Abilify and Geodon, are now being prescribed to more than half a million children in the United States to help parents deal with behavior problems despite almost no approved uses for minors.

A New York Times analysis of records in Minnesota, the only state that requires public reports of all drug company marketing payments to doctors, provides rare documentation of how financial relationships correspond to the growing use of atypicals in children.

From 2000 to 2005, drug maker payments to Minnesota psychiatrists rose more than sixfold, to $1.6 million. During those same years, prescriptions of antipsychotics for children in Minnesota's Medicaid program rose more than ninefold.

Those who took the most money from makers of atypicals tended to prescribe the drugs to children the most often, the data suggest. On average, Minnesota psychiatrists who received at least $5,000 from atypical makers from 2000 to 2005 appear to have written three times as many atypical prescriptions for children as psychiatrists who received less or no money.

The analysis focused on prescriptions written for about one-third of Minnesota's Medicaid population, almost all of whom are disabled.

The analysis shows that from 1997 through 2005, more than a third of Minnesota's licensed psychiatrists took money from drug makers, including the last eight presidents of the Minnesota Psychiatric Society.

Drug makers underwrite decision makers at every level of care. They pay doctors who prescribe and recommend drugs, teach about the underlying diseases, perform studies and write guidelines that other doctors often feel bound to follow.

But studies present strong evidence that financial interests can affect decisions, often without people realizing it.

In Minnesota, psychiatrists collected more money from drug makers from 2000 to 2005 than doctors in any other specialty. Total payments to individual psychiatrists ranged from $51 to more than $689,000, with a median of $1,750. Since the records are incomplete, these figures probably underestimate doctors' actual incomes.

Such payments could encourage psychiatrists to use drugs in ways that endanger patients' physical health, said Dr. Steven Hyman, the provost of Harvard University and former director of the National Institute of Mental Health. The growing use of atypicals in children is the most troubling example of this, Hyman said.

Anya Bailey is a 15-year-old high school freshman from East Grand Forks, Minn., with pictures of the actor Chad Michael Murray on her bedroom wall. She has constant discomfort in her neck that leads her to twist it in a bird-like fashion. Now she slumps when seated at school to pressure her clenched muscles, she said.

It all began in 2003 when Anya became dangerously thin.

Psychiatrists at the University of Minnesota, overseen by Dr. George Realmuto, settled on Risperdal, not for its calming effects but for its normally unwelcome side effect of increasing appetite and weight gain, Bailey said. Anya also had other issues that may have recommended Risperdal to doctors, including occasional angry outbursts and having twice heard voices over the previous five years, Bailey said.

Realmuto said he did not remember Anya's case, but he defended his unapproved use of Risperdal to counter an eating disorder despite the drug's risks. "When things are dangerous, you use extraordinary measures," he said.

Ten years ago, Realmuto helped conduct a study of Concerta, an attention deficit hyperactivity disorder drug marketed by Johnson Johnson, which also makes Risperdal. When Concerta was approved, the company hired him to lecture about it.

Realmuto said he could understand someone worrying that his Concerta lecture fees would influence him to prescribe Concerta, but not a different drug from the same company, like Risperdal.

In general, he conceded, his relationship with a drug company might prompt him to try a drug. Whether he continued to use it, though, would depend entirely on the results.

As the interview continued, Realmuto said that upon reflection his payments from drug companies had probably opened his door to useless visits from a drug salesman, and he said he would stop giving sponsored lectures in the future.

No one has proved that psychiatrists prescribe atypicals to children because of drug company payments. Indeed, some who frequently prescribe the drugs to children earn no drug industry money. And nearly all psychiatrists who accept payments say they remain independent.

"If someone takes the point of view that your doctor can be bought, why would you go to an ER with your injured child and say, 'Can you help me?'" said Dr. Suzanne Albrecht, a psychiatrist from Edina who earned more than $188,000 from 2002 to 2005 giving drug marketing talks.

It is illegal for drug makers to pay doctors directly to prescribe specific products. Federal rules also bar manufacturers from promoting unapproved, or off-label, uses for drugs.

But doctors are free to prescribe as they see fit, and drug companies can sidestep marketing prohibitions by paying doctors to give lectures in which, if asked, they may discuss unapproved uses.

The issue is particularly important in psychiatry, because treatment often involves trial and error and off-label prescribing is common.

Atypicals have become popular because they can settle almost any extreme behavior, often within minutes, and doctors have few other answers for desperate families.

Their growing use in children is closely tied to the increasingly common and controversial diagnosis of pediatric bipolar disorder, a mood problem marked by aggravation, euphoria, depression and, in some cases, violent outbursts. The drugs, sometimes called major tranquilizers, act by numbing brain cells to surges of dopamine, a chemical that has been linked to euphoria and psychotic delusions.

Suzette Scheele, of Burnsville, said her 17-year-old son, Matt, was given a diagnosis of bipolar disorder four years ago because of intense mood swings, and now takes Seroquel and Abilify, which have caused substantial weight gain.

"But I don't have to worry about his rages, he's appropriate, he's pleasant to be around," Scheele said.

The sudden popularity of pediatric bipolar diagnosis has coincided with a shift from antidepressants like Prozac to far more expensive atypicals. In 2000, Minnesota spent more than $521,000 buying antipsychotic drugs, most of it on atypicals, for children on Medicaid. In 2005, the cost was more than $7.1 million, a 14-fold increase.

The drugs, which can cost $1,000 to $8,000 for a year's supply, are huge sellers worldwide. In 2006, Zyprexa, made by Eli Lilly, had $4.36 billion in sales, Risperdal $4.18 billion and Seroquel, made by AstraZeneca, $3.42 billion.

Many Minnesota doctors, including the president of the Minnesota Psychiatric Society, said drug makers and their intermediaries are now paying them almost exclusively to talk about bipolar disorder.

Yet childhood bipolar disorder is an increasingly controversial diagnosis. Even doctors who believe it is common disagree about its telltale symptoms. Others suspect it is a fad. And the scientific evidence that atypicals improve these children's lives is scarce.

Some psychiatrists who advocate use of atypicals in children acknowledge that the evidence supporting this use is thin. But they say children should not go untreated simply because scientists have failed to confirm what clinicians already know.

"We don't have time to wait for them to prove us right," said Dr. Kent Brockmann, a psychiatrist from the Twin Cities who made more than $16,000 from 2003 to 2005 doing drug talks and one-on-one sales meetings, and last year was a leading prescriber of atypicals to Medicaid children.

For Anya Bailey, treatment with an atypical helped her regain her appetite and put on weight, but also heavily sedated her, her mother said. She developed the disabling knot in her back, the result of a nerve condition called dystonia, in 2005.

The reaction was rare but not unknown. Atypicals have side effects that are not easy to predict in any one patient.

In 2006, the Food and Drug Administration received reports of at least 29 children dying and at least 165 more suffering serious side effects in which an antipsychotic was listed as the "primary suspect." That was a substantial jump from 2000, when there were at least 10 deaths and 85 serious side effects among children linked to the drugs. Since reporting of bad drug effects is mostly voluntary, these numbers likely represent a fraction of the toll.

Other psychiatrists renewed Anya's prescriptions for Risperdal until Bailey took Anya last year to the Mayo Clinic, where a doctor insisted Bailey stop the drug.

Unlike most universities and hospitals, the Mayo Clinic restricts doctors from giving drug marketing lectures.

Bailey said she wished she had waited to see whether counseling would help Anya before trying drugs.

Anya's weight is now normal without the help of drugs, and her counseling ended in March. An experimental drug, her mother said, has recently helped the pain in her back.

Source: Published in the St. Paul Pioneer Press and the Minneapolis Star Tribune - May 2007

Tue Feb 13, 2007 4:06PM EST

WASHINGTON, Feb 13 (Reuters) - U.S. lawmakers should investigate the Food and Drug Administration's handling of side effects linked to Eli Lilly and Co.'s (LLY.N: Quote, Profile, Research) antipsychotic medication, Zyprexa, an agency whistleblower said on Tuesday.

FDA scientist Dr. David Graham told a congressional hearing the drugmaker and the agency knew "for a long time" about the risk of weight gain from Zyprexa that could trigger diabetes.

While such side effects were eventually added to the drug's prescribing instructions, Graham testified it was not clear how the agency handled the information or made the decision to alter the label.

"FDA did its typical dragging its feet on post-marketing safety issues," he told Reuters after the U.S. House of Representatives Energy and Commerce subcommittee hearing.

Graham did not review Zyprexa, but said that, after his 2004 public testimony criticizing the FDA's actions on Merck & Co Inc.'s (MRK.N: Quote, Profile, Research) withdrawn Vioxx painkiller, other agency staffers came to him with concerns.

Zyprexa, approved in 1996, is cleared to treat schizophrenia and bipolar disorder.

Other antipsychotic medications also warrant closer scrutiny, Graham told lawmakers without naming specific drugs. He also said he would submit a list of other types of prescription drugs with safety concerns that the committee should investigate.

Antipsychotics include Bristol-Myers Squibb's (BMY.N: Quote, Profile, Research) Abilify, Novartis AG's (NOVN.VX: Quote, Profile, Research)(NVS.N: Quote, Profile, Research) Clozaril, Lilly's Symbyax, AstraZeneca Plc's (AZN.L: Quote, Profile, Research)(AZN.N: Quote, Profile, Research) Seroquel, Johnson & Johnson's (JNJ.N: Quote, Profile, Research) Risperdal and Pfizer Inc.'s (PFE.N: Quote, Profile, Research) Geodon, among others.

Such drugs are increasingly being given for unapproved uses to nursing home patients with dementia and similar mental disorders, which can double the risk of death, he said.

Although the FDA does not regulate the use of medicines once they are approved, Graham called the problem a "public health issue."

Representatives for the FDA and Eli Lilly could not be immediately reached for comment.

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UNITED STATES DISTRICT COURT
EASTERN DISTRICT OF NEW YORK

LOCAL 28 SHEET METAL                                                  
WORKERS on behalf of themselves
And other similarly situated

Thomas M. Sobol

David S. Nalven

Lauren G. Barnes

Hagens Berman Sobol Shapiro

One Main Street, 4th Floor

Cambridge, MA 02142

Telephone: (617) 482-3700

 

Jason Thompson

Ann Mandt

Charfoos & Christensen, P.C.

5510 Woodward Avenue

Detroit, Mi 48202

Telephone (313) 875-8080

 

Ronald Goldser

Timothy Becker

Zimmerman Reed

651 Nicollet Mall, Suite 501

Minneapolis, MN 55402

Telephone (612) 341-0400

 

Attorneys for Plaintiff

Plaintiffs
v.                                                                                
ELI LILLY AND COMPANY
Defendant


I.                    INTRODUCTION

This is a proposed national class action on behalf of consumers and third party  payors (self-insured employers, Taft-Hartley funds, non-profit and for-profit health insurers, all of whom bear the ultimate risk for prescription drug expense) against Eli Lilly & Company ("Lilly" or "Defendant") seeking damages and other monetary relief by reason of Lilly's wrongful and illegal marketing, sales and promotional activities for the atypical antipsychotic Zyprexa.

EXCERPT EXTRACTED FROM PAGES 73 – 75

7. National Alliance for the Mentally Ill (NAMI) Activities

192. Lilly also utilized a non-profit organization as a front to further its own purposes of increasing market share for atypical antipsychotics and other medications. Lilly's funding and partnering with the National Alliance for the Mentally Ill (NAMI) in the late 1990s and early 2000s was designed to accomplish through a non-profit organization what it could not on its own: giving the appearance of independent analysis and a grassroots movement encouraging the use of atypical antipsychotics by state and private insurers. The scheme worked and Lilly certainly benefited from its significant donations to NAMI. Zyprexa was the leading antipsychotic in the world in 2000, capturing nearly 40% of the global antipsychotic market. A year later, Zyperexa was the sixth highest selling pharmaceutical product in the world, with $3.2 billion in sales.

193.    NAMI is a national association of mental health organizations in every state and bills itself as "redacted from court record". In reality, this not-for profit organization readily accepts donations offered by pharmaceutical manufacturers while "redacted from court record".

194.    Lilly has been the largest contributor among pharmaceutical manufacturers to NAMI, giving the organization approximately $2.87 million between 1996 and 1999.

195.    Lilly "donations" to NAMI were not limited to money. In 1999, Mother Jones Magazine reported that Lilly executive Jerry Radke was "on loan" to NAMI as an executive. Also in 1999, Bob Postlethwait, a Lilly executive who headed the group that produced and marketed Zyprexa (and Prozac assisted NAMI Indiana in securing government funding for an executive director.

196.    Lilly also provided funding for a variety of brochures and programs produced by NAMI highlighting the use of atypical antipsychotics. One such Lilly-funded brochure – "Understanding Schizophrenia" – produced by NAMI for patients and families of schizophrenics minimized the side effects of atypical antipsychotics such as Zyprexa. Another – the 2001 "Access to Effective Medications" brochure produced by NAMI National for legislators and paid for by Lilly – lays out a blueprint for nationwide NAMI lobbying of state governments to reduce or remove any limitations to payments for atypical antipsychotics, again down-playing the side effects of such drugs.

197.    Using money from Lilly and other pharmaceutical companies, NAMI – both the various state-level association and the national organization – has effectively lobbied state and federal governments to increase spending on atypical antipsychotic drugs and to reduce restrictions on access to those pharmaceuticals, thereby protecting pharmaceutical industry profits through the guise of independent, grassroots advocacy. For example, between 1998 and 2000, Lilly gave NAMI Washington State $91,000. During that time, NAMI Washington State, in an effort led by NAMI lobbyist Brad Boswell, lobbied the state legislature for $1 million specifically for atypical antipsychotic drugs. Brad Boswell was Lilly's Washington state lobbyist just prior to his assignment with NAMI Washington State. NAMI also join a suit initiated by the Pharmaceutical Research and Manufacturers of America (PhRMA) against the state of Michigan in order to increase physician access to higher cost pharmaceuticals – including atypical antipsychotics – under the state's Medicaid program.

198. The U.S. Department of Health and Human Services Office of the Inspector General issued a report in 2002 warning that cozy financial relationships between non-profit advocacy groups and pharmaceutical companies – such as the one between NAMI and Lilly – which result in the generation of revenue for the pharmaceutical companies could be considered illegal under the federal anti-kickback statute.