NOT OT/NYTimes: Psychiatrists, Children and Drug Industry’s Role

[Guest guest]

" Just as surprising, Ms. said, was learning that the university

psychiatrist who supervised Anya’s care received more than $7,000 from

2003 to 2004 from & , Risperdal’s maker, in return for

lectures about one of the company’s drugs. "

Psychiatrists, Children and Drug Industry’s Role

Fabrizio Costantini for The New York Times

Anya is among a growing number of children given antipsychotic

drugs by doctors who are paid by the makers of those drugs.

By GARDINER HARRIS, BENEDICT CAREY and JANET ROBERTS

Published: May 10, 2007

When Anya developed an eating disorder after her 12th birthday,

her mother took her to a psychiatrist at the University of Minnesota

who prescribed a powerful antipsychotic drug called Risperdal.

Prescription for Influence

Beyond the Label

The New York Times

Enlarge This Image

Fabrizio Costantini for The New York Times

Anya has a painful nerve condition called dystonia, in which the

muscles in her back clench as a result of taking an antipsychotic drug.

Enlarge This Image

Fabrizio Costantini for The New York Times

Anya with her younger sister, , and her mother, Isabella.

Created for schizophrenia, Risperdal is not approved to treat eating

disorders, but increased appetite is a common 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 back muscles. She often awakens

crying in pain.

Isabella , Anya’s mother, said she had no idea that children

might be especially susceptible to Risperdal’s side effects. Nor did

she know that Risperdal and similar medicines were not approved at the

time to treat children, or that medical trials often cited to justify

the use of such drugs had as few as eight children taking the drug by

the end.

Just as surprising, Ms. said, was learning that the university

psychiatrist who supervised Anya’s care received more than $7,000 from

2003 to 2004 from & , Risperdal’s maker, in return for

lectures about one of the company’s drugs.

Doctors, including Anya ’s, maintain that payments from drug

companies do not influence what they prescribe for patients.

But the intersection of money and medicine, and its effect on the

well-being of patients, has become one of the most contentious issues

in health care. 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 profound risks and 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

between doctors and drug makers 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 Times analysis focused on prescriptions written for about one-third

of Minnesota’s Medicaid population, almost all of whom are disabled.

Some doctors were misidentified by pharmacists, but the information

provides a rough guide to prescribing patterns in the state.

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 knowing 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. E. 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, Dr. Hyman said.

“There’s an irony that psychiatrists ask patients to have insights into

themselves, but we don’t connect the wires in our own lives about how

money is affecting our profession and putting our patients at risk,” he

said.

The Prescription

Anya is a 15-year-old high school freshman from East Grand

Forks, Minn., with pictures of the actor Chad Murray on her

bedroom wall. She has constant discomfort in her neck that leads her to

twist it in a birdlike fashion. Last year, a boy mimicked her in the

lunch room.

“The first time, I laughed it off,” Anya said. “I said: ‘That’s so

funny. I think I’ll laugh with you.’ Then it got annoying, and I

decided to hide it. I don’t want to be made fun of.”

Now she slumps when seated at school to pressure her clenched muscles,

she said.

It all began in 2003 when Anya became dangerously thin. “Nothing tasted

good to her,” Ms. said.

Psychiatrists at the University of Minnesota, overseen by Dr. M.

Realmuto, settled on Risperdal, not for its calming effects but for its

normally unwelcome side effect of increasing appetite and weight gain,

Ms. said. Anya had other issues that may have recommended

Risperdal to doctors, including occasional angry outbursts and having

twice heard voices over the previous five years, Ms. said.

Dr. Realmuto said he did not remember Anya’s case, but speaking

generally 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, Dr. Realmuto helped conduct a study of Concerta, an

attention deficit hyperactivity disorder drug marketed by &

, which also makes Risperdal. When Concerta was approved, the

company hired him to lecture about it.

He said he gives marketing lectures for several reasons.

“To the extent that a drug is useful, I want to be seen as a leader in

my specialty and that I was involved in a scientific study,” he said.

The money is nice, too, he said. Dr. Realmuto’s university salary is

$196,310.

“Academics don’t get paid very much,” he said. “If I was an

entertainer, I think I would certainly do a lot better.”

In 2003, the year Anya came to his clinic, Dr. Realmuto earned $5,000

from & for giving three talks about Concerta. Dr.

Realmuto said he could understand someone’s 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, Dr. 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.

Kara , a & spokeswoman, said that the company

selects speakers who have used the drug in patients and have either

undertaken research or are aware of the studies. “Dr. Realmuto met

these criteria,” Ms. said.

When asked whether these payments may influence doctors’ prescribing

habits, Ms. said that the talks “provide an educational

opportunity for physicians.”

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. Some say

they prescribed and extolled the benefits of such drugs before ever

receiving payments to speak to other doctors about them.

“If someone takes the point of view that your doctor can be bought, why

would you go to an E. R. with your injured child and say, ‘Can you help

me?’ ” said Dr. Suzanne A. Albrecht, a psychiatrist from Edina, Minn.,

who earned more than $188,000 from 2002 to 2005 giving drug marketing

talks.

The Industry Campaign

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 drug industry and many doctors say that these promotional lectures

provide the field with invaluable education. Critics say the payments

and lectures, often at expensive restaurants, are disguised kickbacks

that encourage potentially dangerous drug uses. The issue is

particularly important in psychiatry, because mental problems are not

well understood, treatment often involves trial and error, and

off-label prescribing is common.

The analysis of Minnesota records 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.

The psychiatrist receiving the most from drug companies was Dr. Annette

M. Smick, who lives outside Rochester, Minn., and was paid more than

$689,000 by drug makers from 1998 to 2004. At one point Dr. Smick was

doing so many sponsored talks that “it was hard for me to find time to

see patients in my clinical practice,” she said.

“I was providing an educational benefit, and I like teaching,” Dr.

Smick said.

Dr. S. Sharfstein, immediate past president of the American

Psychiatric Association, said psychiatrists have become too cozy with

drug makers. One example of this, he said, involves Lexapro, made by

Forest Laboratories, which is now the most widely used antidepressant

in the country even though there are cheaper alternatives, including

generic versions of Prozac.

“Prozac is just as good if not better, and yet we are migrating to the

expensive drug instead of the generics,” Dr. Sharfstein said. “I think

it’s the marketing.”

Atypicals have become popular because they can settle almost any

extreme behavior, often in 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, Minn., 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,” Ms. 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.

The Diagnoses

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.

One of the first and perhaps most influential studies was financed by

AstraZeneca and performed by Dr. DelBello, a child and adult

psychiatrist at the University of Cincinnati.

Dr. DelBello led a research team that tracked for six weeks the moods

of 30 adolescents who had received diagnoses of bipolar disorder. Half

of the teenagers took Depakote, an antiseizure drug used to treat

epilepsy and bipolar disorder in adults. The other half took Seroquel

and Depakote.

The two groups did about equally well until the last few days of the

study, when those in the Seroquel group scored lower on a standard

measure of mania. By then, almost half of the teenagers getting

Seroquel had dropped out because they missed appointments or the drugs

did not work. Just eight of them completed the trial.

In an interview, Dr. DelBello acknowledged that the study was not

conclusive. In the 2002 published paper, however, she and her

co-authors reported that Seroquel in combination with Depakote “is more

effective for the treatment of adolescent bipolar mania” than Depakote

alone.

In 2005, a committee of prominent experts from across the country

examined all of the studies of treatment for pediatric bipolar disorder

and decided that Dr. DelBello’s was the only study involving atypicals

in bipolar children that deserved its highest rating for scientific

rigor. The panel concluded that doctors should consider atypicals as a

first-line treatment for some children. The guidelines were published

in The Journal of the American Academy of Child and Adolescent

Psychiatry.

Three of the four doctors on the panel served as speakers or

consultants to makers of atypicals, according to disclosures in the

guidelines. In an interview, Dr. A. Kowatch, a psychiatrist at

Cincinnati Children’s Hospital and the lead author of the guidelines,

said the drug makers’ support had no influence on the conclusions.

AstraZeneca hired Dr. DelBello and Dr. Kowatch to give sponsored talks.

They later undertook another study comparing Seroquel and Depakote in

bipolar children and found no difference. Dr. DelBello, who earns

$183,500 annually from the University of Cincinnati, would not discuss

how much she is paid by AstraZeneca.

“Trust me, I don’t make much,” she said. Drug company payments did not

affect her study or her talks, she said. In a recent disclosure, Dr.

DelBello said that she received marketing or consulting income from

eight drug companies, including all five makers of atypicals.

Dr. Realmuto has heard Dr. DelBello speak several times, and her talks

persuaded him to use combinations of Depakote and atypicals in bipolar

children, he said. “She’s the leader in terms of doing studies on

bipolar,” Dr. Realmuto said.

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

G. 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.

The Reaction

For Anya , 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. These include rapid weight

gain and blood sugar problems, both risk factors for diabetes;

disfiguring tics, dystonia and in rare cases heart attacks and sudden

death in the elderly.

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.

Jim Minnick, a spokesman for AstraZeneca, said that the company

carefully monitors reported problems with Seroquel. “AstraZeneca

believes that Seroquel is safe,” Mr. Minnick said.

Other psychiatrists renewed Anya’s prescriptions for Risperdal until

Ms. took Anya last year to the Mayo Clinic, where a doctor

insisted that Ms. stop the drug. Unlike most universities and

hospitals, the Mayo Clinic restricts doctors from giving drug marketing

lectures.

Ms. 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.

This article is by Gardiner , Benedict Carey and Janet .