'Medicating' children with powerful, toxic psychiatric drugs.

St. Petersburg Times 

 The 'atypical' dilemma

Skyrocketing numbers of kids are prescribed powerful antipsychotic drugs. Is it safe? Nobody knows.

ROBERT FARLEY   
Times Staff Writer
July 29, 2007

More and more, parents at wit's end are begging doctors to help them calm their aggressive children or control their kids with ADHD. More and more, doctors are prescribing powerful antipsychotic drugs.

In the past seven years, the number of Florida children prescribed such drugs has increased some 250 percent. Last year, more than 18,000 state kids on Medicaid were given prescriptions for antipsychotic drugs.

Even children as young as 3 years old. Last year, 1,100 Medicaid children under 6 were prescribed antipsychotics, a practice so risky that state regulators say it should be used only in extreme cases.

These numbers are just for children on fee-for-service Medicaid, generally the poor and disabled. Thousands more kids on private insurance are also on antipsychotics.

Almost entirely driving this spiraling trend is the rise of a class of antipsychotic drugs called atypicals.

These drugs emerged in the 1990s and replaced the older, "typical" antipsychotics like Haldol or Thorazine, which are often associated with Parkinson-like shakes.

The atypicals were developed to treat schizophrenia and bipolar disorder in adults. But once on the market, doctors are free to prescribe them to children, and for uses not approved by the Food and Drug Administration.

There is almost no research on the long-term effects of such powerful medications on the developing brains of children. The more that researchers learn, the less comfortable many are becoming with atypicals.

Initially billed as wonder drugs with few significant side effects, evidence is mounting that they can cause rapid weight gain, diabetes, even death.

They're also expensive. On average last year, it cost Medicaid nearly $1,800 for each child on atypical antipsychotics. In the last seven years, the cost to taxpayers for atypical antipsychotics prescribed to children in Florida jumped nearly 500 percent, from $4.7-million to $27.5-million.

Medicaid and insurance companies have fed the problem, encouraging the use of psychiatric drugs as they reimburse less and less for labor-intensive psychotherapy and occupational therapy.

Another factor: Doctors have been influenced by pharmaceutical companies, which have aggressively marketed atypicals.

Whatever the reasons for the soaring use of psychiatric drugs in children, things have gotten out of whack, according to Dr. Ronald Brown. Last year he headed an American Psychological Association committee that looked into the issue.

"The bottom line is that the use of psychiatric medications far exceeds the evidence of safety and effectiveness," Brown said.

"What people need to do is what's in the best interest of children instead of what's in the best interest of people's pocketbooks. But children don't vote."

* * *

The ever-increasing number of kids who come through the doors of pediatrician Esther Gonzalez's office lead chaotic lives. There's more divorce and more drug use, more domestic violence and physical and sexual abuse. Working parents are overwhelmed.

"Some parents are so stressed out, they come in seeking a pill," Gonzalez said. It is easy to medicate kids; "it is very hard to change environment."

At her practice in Crystal River, she starts with a thorough screening. A child might need occupational, physical or speech therapy. Sometimes, it takes psychiatric drugs.

Despite her concerns about prescribing such medications, Gonzalez has no doubt they have saved many a child from juvenile detention.

Not prescribing drugs to a child who needs them, she said, "it's like seeing someone dying and not giving them CPR."

Among her patients is 7-year-old Matthew Peck of Brooksville. His 13-year-old brother and 16-year-old sister show scars on their arms and legs where he has bitten them. He flies into rages, kicks, scratches and pulls hair. He destroys furniture and punches holes in the wall.

His mom, Cathy Peck, said Matthew's doctors are "leaning toward" a diagnosis of oppositional defiance disorder. And he has attention-deficit hyperactivity disorder (ADHD).

Matthew has taken a 5 mg dose of the atypical Abilify for over two months now. He says "the blue pill" makes him feel like a different person, someone nice.

Peck, a single mother on disability from the Army National Guard, says she worries the drugs may become addictive. And diabetes runs in the family, so that's a concern. Then again ... a few months ago Matthew got hold of a steak knife and destroyed a chair.

"Am I afraid of what the medications might do to him? Yes," Peck said. "But I am also afraid of what his life would be like without them."

Matthew and his brother are playing. Suddenly Matthew raises a hand to hit him.

"Gather!" Cathy Peck yells, the trigger word to help Matthew calm himself.

He lowers his hand, shambles over to his mother, curls up behind her. Crisis avoided.

Matthew's 13-year-old sister, Marradith, said the Abilify works. "He's a different person. He's more fun to be around. He doesn't attack me anymore."

The meds help, Mom says, but therapy is integral to Matthew's treatment. She was taking him to eight sessions a week of occupational, speech and language therapy.

Matthew recently had his last occupational therapy session - but not by choice. After six years, Sensations Pediatrics Therapy in Brooksville closed shop on June 15.

That last day of business, Sensations owner Jeff Leonbruno lamented how hard it is for therapists to stay afloat. Particularly with pediatric therapy sessions, he said, there is a high cancellation and no-show rate, often four or five a day. If they don't show, he can't charge.

"It's difficult to make a living at it," Leonbruno said.

Insurance companies and Medicaid don't pay enough for therapy, he said. They do, however, pay to reimburse for psychiatric medications.

Over the years, he said, Medicaid priorities have shifted toward the elderly in nursing homes. That has put a pinch on services like occupational therapy for children with behavioral disorders.

"There's no AARP for kids," he said.

* * *

Before the FDA approves a new drug, pharmaceutical companies must demonstrate its safety and efficacy. The trials generally are done on adults.

But once the drugs are on the market, doctors are free to prescribe the drug "off label," outside the scope of the FDA's indicated use. They also can prescribe it to children.

Except for Risperdal, none of the antipsychotics is FDA-approved for children. The overwhelming majority are prescribed "off label."

"It is alarming how frequently that is being done," Brown said. "It's of concern that it is being done at all."

A child's brain and central nervous system are still developing, so drugs work differently on kids than adults, Brown said. "There are no studies that have shown they (atypicals) are safe, or for that matter, that they are effective for children."

Drug companies have little incentive to invest in such studies, given that their products already are widely prescribed to children off label.

The antipsychotics are FDA-approved for adults with schizophrenia and bipolar disorder, which used to be known as manic depression. But a study by the University of South Florida found that just 8 percent of Florida children prescribed antipsychotics last year had a primary diagnosis of schizophrenia, and 8 percent had major depression. The most common diagnosis, 38 percent, was ADHD.

Even with bipolar disorder, there is considerable debate in the mental health community about whether it is overdiagnosed, particularly in younger children.

Dr. Mark Olfson of Columbia University studied the use of antipsychotics in children and concluded that only a small percentage had psychotic disorders. Most were used to treat mood disorders, depression, anxiety and ADHD - by families and doctors who have tried everything else and are ready to step outside the well-established treatments and take more risks.

"Most child psychiatrists would probably tell you it does work," Olfson said. "But there is a real need for research, clinical experiments, to determine whether in fact it does work. Given the number of young people, it is a matter of urgency."

Mental health practitioners say they use more antipsychotics now in part because they are better able to identify some mental illnesses, including autism.

Never mind that the National Autism Association warns against the overuse of atypicals for children with autism. Last year, when Risperdal became the first and only atypical approved for use in children - specifically for irritability associated with autism - the association warned against potentially serious side effects, including lactation in boys, weight gain and development of an often irreversible movement disorder.

Rita Shreffler, the autism association's executive director, said antipsychotics should be used only for dangerously aggressive children, and even then only for a short "leveling off period."

Dr. Randall Stafford, an associate professor of medicine at Stanford Prevention Research Center, says off-label prescribing allows doctors the latitude to innovate.

But Stafford was the lead author of a study that concluded that most off-label medication occurs without enough scientific support.

Some prescriptions have become so common, he said, "You have to ask, 'Where is the data to support this use of the drug?' It's not that these off-label uses are dangerous. It's that we just don't know."

* * *

Kate Malloy knows what people will think: Every kid throws tantrums; parents just need to discipline their children.

But with 10-year-old Ryan, she said, the outbursts were beyond aggressive. He seemed outside himself.

A psychologist diagnosed bipolar disorder and recommended they see a psychiatrist.

"You are under the impression that when you go to the doctor you'll be fixed," she said. "And that isn't how it works. They don't, by any means, have all the answers."

The ADHD medication Ryan was prescribed only inflamed things, and therapy fell flat. They tried atypicals, first Risperdal. Then Zyprexa. Then Seroquel.

"In the beginning, when the meds weren't working, I hated them," she said. "I hated that they were the only option."

She took Ryan off all the medications and tried an alternative doctor, who recommended dietary supplements. That worked, but only for a while.

She went to Dr. Mark Cavitt, medical director of pediatric psychiatry at All Children's Hospital in St. Petersburg.

He says mental health practitioners operate in gray areas. The unknowns of the long-term effects of psychotropic drugs have to be balanced against the risk of not treating.

Studies show that atypicals can be effective in modifying aggressive behavior, he said, and that kids who are treated for depression and schizophrenia are less likely to fall prey to pitfalls like drug abuse and teen pregnancy. Then again: "We have to be concerned. There is no such thing as a benign psychiatric medication."

Dr. Cavitt prescribed Risperdal for Ryan. He couldn't tell when he was full and gained 15 pounds. When Risperdal stopped working, they switched to Abilify.

Mom hates to think about the possible long-term effects but has more immediate concerns, like, "Will he jump out of a moving car?"

"There are certainly downsides to medications," she said. "But when medications don't work, we are pretty much screwed. There are not a lot of options."

* * *

At the Suncoast Center for Community Health in Clearwater, the focus is on therapy. Drugs are a last resort.

Renee Kilroy, the clinical director, said the sharp increase in psychotropic medications to children is unsettling. "It's not my belief we need to put more kids on medications. They are still growing and changing."

Therapy costs more in the short term, she said, but a lifetime of medications is costlier. Suncoast can afford to take the longer view thanks to subsidies it gets from the county's Juvenile Welfare Board.

More and more, she said, they get referrals from the school system for disruptive kids. Parents tell her that the school has told them their children need to be put on psychiatric medication before they can come back - even though state law specifically forbids that.

* * *

Children younger than 6 generally should not be given psychotropic drugs. According to guidelines from the Florida Agency for Health Care Administration, it should "only be considered under the most extraordinary of circumstances."

Last year, 1,111 Florida Medicaid children younger than 6 were prescribed antipsychotics.

There is no recommendation for the use of antidepressants in children younger than 6 - yet 629 children were prescribed antidepressants last year.

Using stimulant medications for ADHD should be "rare" for kids younger than 4, the guidelines state, "and only after a failed behavioral intervention such as parent training." Last year, 367 toddlers 3 and younger were prescribed ADHD medications.

Cavitt said 3-year-olds put on psychotropic medications typically are autistic, mentally retarded or brain injured. They are extremely self-injurious or physically aggressive to others, he said.

Robert Whitaker, a journalist and author of the book Mad in America, says there is no circumstance where it makes sense to prescribe an antipsychotic drug to a 3-year-old.

"It is not a scientific use of drugs," Whitaker said. "It is an experiment. There is no data showing that they are helpful in a 3-year-old kid. None. Zero. Zip."

Rather, he said, it is using medication as a controlling device. Whitaker blames a system of "assembly line medicine," where psychiatrists are afforded less and less time with patients. Atypicals provide a shortcut to dealing with unruly children.

"It mutes your ability to respond to the world, emotionally and physically," he said. "They make them easier to manage, to others."

The pharmaceutical companies also help to shape the prescribing patterns, he said. The law forbids them from openly marketing to children off-label, but as any child psychiatrist will tell you, pharmaceutical reps for the atypicals are regular visitors.

Psychiatrists like Cavitt say the reps know the line: They are there only to provide company research and to solicit feedback on the use of their medications.

But Whitaker said it's clear why the reps for atypicals are in the offices of child psychiatrists: "They do it because they know it's effective in promoting off-label uses of their drugs.

"They are publicly traded companies trying to maximize their revenues. It increases off-label use, and doctors should quit pretending otherwise."

Minnesota is the only state that requires public reports of all drug company marketing payments to doctors. A recent New York Times analysis of those records found that doctors who took the most money from makers of atypicals tended to prescribe the drugs to children the most.

* * *

The support group for people whose relatives have committed suicide was unveiling a quilt with squares in memory of each person.

Kathy Pingleton was seated in a plastic chair in the back row when her son's name was called.

"Brandon Lee Pingleton."

Her husband, Ken, put his arm around her and they made their way to the front.

Kathy stole a glance at the section of quilt she made in honor of Brandon, a 15-year-old sophomore at Largo High School.

She worried that she made the square too busy. Lots of pictures and buttons to show Brandon's love of football, soccer and karate.

Kathy reached out a hand to light a candle in his memory. On one finger was a ring made of a guitar string that Brandon used. It reminds her of his artistic side.

Nearly four years ago she and Ken found Brandon hanging in his bedroom, just feet from where they were.

Diagnosed with ADHD, Brandon had landed in a county crisis center after he overdosed on Robitussin and told authorities he was depressed.

When he was released from the center, mom remembers taking him to a psychiatrist. After 5 minutes of evaluation - "How are you sleeping? How is school?" - the doctor doubled his dosage of the atypical antipsychotic Seroquel.

She remembers wondering why he was taking the drug when the Web site said it was for schizophrenia and bipolar disorder.

She hated what the drugs did to him, as did Brandon. He said it made him feel like a zombie.

Seroquel now carries a black box warning that antidepressants may increase the risk of suicidal thoughts in children and teenagers, and that patients should be watched closely.

Those warnings didn't come until 2004. Brandon hanged himself in 2003.

* * *

Alan Levine ran the state's Agency for Health Care Administration in 2005. He became so alarmed by the spike in antipsychotics prescribed to children that he contracted with USF to study the trend.

The study found that from mid 2002 to mid 2004, the cost of psychotropic drug prescriptions for kids increased 60 percent. Pacing that increase was an 82 percent jump in spending on atypical antipsychotics.

"It has very quietly grown as a problem," Levine said.

He wanted to reel it in, but not in a knee-jerk way that might hurt kids who need medications. "There needs to be a more sane and evidence-based approach when prescribing these drugs to children."

The use of antidepressants and ADHD medications dropped and the growth of antipsychotics slowed over a two-year period, starting in April 2004.

By then, said Robert Constantine at USF's Louis De La Parte Mental Health Institute, any psychiatrist would have been aware of the metabolic side effects of the new antipsychotics, and, for those taking antidepressants, the dangers of suicidal feelings.

As part of the $3-million state grant, USF was charged with sending out letters to physicians who were regularly prescribing outside the accepted guidelines.

For example, in the first quarter of this year, 315 children on Medicaid got antipsychotics at higher-than-recommended dosage levels.

Another common problem, Constantine said, was the practice of prescribing more than one antipsychotic at a time. Some doctors swear it works, but there isn't much scientific evidence to back that up. The first three months this year, 274 children were prescribed two or more antipsychotics for an extended period.

Joanne Mills' 12-year-old son was on 16 medications. At the same time.

"At the time we decided to put him on each one of them there was a good reason for it, or else we wouldn't have done it," said Mills, a mother of six in Homosassa.

In the last year, by integrating therapy, she said they have cut her son's 16 medications to three, including the atypical Seroquel.

He has been diagnosed with ADHD and occasionally explosive behavior. For three years, she had to hold him for three hours a night so he could sleep.

Frustrated to the nth degree, she says you walk into the doctor's office with a bubble of hope, and walk out 15 minutes later with a handful of prescriptions, for drugs you've tried before without any lasting benefit.

"The doctors throw their hands up in the air and say, 'I don't know what else to try.' "

About the numbers

Most of the statistics in this story are derived from Medicaid data provided by Florida's Agency for Health Care Administration.

The agency provided the same data to the University of South Florida, which was contracted by the state to study prescribing patterns. As a public service, USF prepared an analysis of the state's data for the St. Petersburg Times.

The numbers include only children on fee-for-service Medicaid. They do not include children in Medicaid HMOs or those with private insurance.

Some 720,000 children were in the fee-for-service Medicaid program last year, out of some 4.5-million children in Florida. That means the statistics in this story vastly underestimate the entire picture of antipsychotic medications prescribed to children.

The Medicaid numbers were used because the program is taxpayer-funded and the information is public.

The atypicals

A new class of drugs emerged in the 1990s, touted as a better and safer way to treat schizophrenia and bipolar disorder. Here are the atypicals now on the market.

Trade name Drug name Marketed by

Clozaril Clozapine Novartis

Zyprexa Olanzapine Eli Lilly and Co.

Risperdal Risperidone Janssen Pharmaceutica

Seroquel Quetiapine AstraZeneca

Geodon Ziprasidone Pfizer

Abilify Aripiprazole Otsuka Pharmaceutical Co.

Invega Paliperidone Janssen Pharmaceutica  

 

Sometimes, Only the Court Jester Is
Allowed Prime Space in the Public Square
from which to Speak the Truth.

this will be replaced by the SWF.



May 10, 2007

Psychiatrists, Children and Drug Industry’s Role

By GARDINER HARRIS, BENEDICT CAREY and JANET ROBERTS

When Anya Bailey 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.

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 Bailey, 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. Bailey said, was learning that the university 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 the company’s drugs.

Doctors, including Anya Bailey’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. Steven 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 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 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. Bailey said.

Psychiatrists at the University of Minnesota, overseen by Dr. George M. Realmuto, settled on Risperdal, not for its calming effects but for its normally unwelcome side effect of increasing appetite and weight gain, Ms. Bailey 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. Bailey 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 Johnson & Johnson, 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 Johnson & Johnson 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 Russell, a Johnson & Johnson 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. Russell said.

When asked whether these payments may influence doctors’ prescribing habits, Ms. Russell 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. Steven 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. Melissa 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. Robert 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 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. 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. Bailey took Anya last year to the Mayo Clinic, where a doctor insisted that Ms. Bailey stop the drug. Unlike most universities and hospitals, the Mayo Clinic restricts doctors from giving drug marketing lectures.

Ms. 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.




September 1, 2010

Child’s Ordeal Shows Risks of Psychosis Drugs for Young

Toddlers are being placed on toxic, anti-psychotic drugs.

By DUFF WILSON

[Right-click here to download a pdf of this article.]

OPELOUSAS, La. — At 18 months, Kyle Warren started taking a daily antipsychotic drug on the orders of a pediatrician trying to quell the boy’s severe temper tantrums.

Thus began a troubled toddler’s journey from one doctor to another, from one diagnosis to another, involving even more drugs. Autism, bipolar disorder, hyperactivity, insomnia, oppositional defiant disorder. The boy’s daily pill regimen multiplied: the antipsychotic Risperdal, the antidepressant Prozac, two sleeping medicines and one for attention-deficit disorder. All by the time he was 3.

He was sedated, drooling and overweight from the side effects of the antipsychotic medicine. Although his mother, Brandy Warren, had been at her “wit’s end” when she resorted to the drug treatment, she began to worry about Kyle’s altered personality. “All I had was a medicated little boy,” Ms. Warren said. “I didn’t have my son. It’s like, you’d look into his eyes and you would just see just blankness.”

Today, 6-year-old Kyle is in his fourth week of first grade, scoring high marks on his first tests. He is rambunctious and much thinner. Weaned off the drugs through a program affiliated with Tulane University that is aimed at helping low-income families whose children have mental health problems, Kyle now laughs easily and teases his family.

Ms. Warren and Kyle’s new doctors point to his remarkable progress — and a more common diagnosis for children of attention-deficit hyperactivity disorder — as proof that he should have never been prescribed such powerful drugs in the first place.

Kyle now takes one drug, Vyvanse, for his attention deficit. His mother shared his medical records to help document a public glimpse into a trend that some psychiatric experts say they are finding increasingly worrisome: ready prescription-writing by doctors of more potent drugs to treat extremely young children, even infants, whose conditions rarely require such measures.

More than 500,000 children and adolescents in America are now taking antipsychotic drugs, according to a September 2009 report by the Food and Drug Administration. Their use is growing not only among older teenagers, when schizophrenia is believed to emerge, but also among tens of thousands of preschoolers.

A Columbia University study recently found a doubling of the rate of prescribing antipsychotic drugs for privately insured 2- to 5-year-olds from 2000 to 2007. Only 40 percent of them had received a proper mental health assessment, violating practice standards from the American Academy of Child and Adolescent Psychiatry.

“There are too many children getting on too many of these drugs too soon,” Dr. Mark Olfson, professor of clinical psychiatry and lead researcher in the government-financed study, said.

Such radical treatments are indeed needed, some doctors and experts say, to help young children with severe problems stay safe and in school or day care. In 2006, the F.D.A. did approve treating children as young as 5 with Risperdal if they had autistic disorder and aggressive behavior, self-injury tendencies, tantrums or severe mood swings. Two other drugs, Seroquel from AstraZeneca and Abilify from Bristol-Myers Squibb, are permitted for youths 10 or older with bipolar disorder.

But many doctors say prescribing them for younger and younger children may pose grave risks to development of both their fast-growing brains and their bodies. Doctors can legally prescribe them for off-label use, including in preschoolers, even though research has not shown them to be safe or effective for children. Boys are far more likely to be medicated than girls.

Dr. Ben Vitiello, chief of child and adolescent treatment and preventive research at the National Institute of Mental Health, says conditions in young children are extremely difficult to diagnose properly because of their emotional variability. “This is a recent phenomenon, in large part driven by the misperception that these agents are safe and well tolerated,” he said.

Even the most reluctant prescribers encounter a marketing juggernaut that has made antipsychotics the nation’s top-selling class of drugs by revenue, $14.6 billion last year, with prominent promotions aimed at treating children. In the waiting room of Kyle’s original child psychiatrist, children played with Legos stamped with the word Risperdal, made by Johnson & Johnson. It has since lost its patent on the drug and stopped handing out the toys.

Greg Panico, a company spokesman, said the Legos were not intended for children to play with — only as a promotional item.

Cheaper to Medicate

Dr. Lawrence L. Greenhill, president of the American Academy of Child and Adolescent Psychiatry, concerned about the lack of research, has recommended a national registry to track preschoolers on antipsychotic drugs for the next 10 years. “Psychotherapy is the key to the treatment of preschool children with severe mental disorders, and antipsychotics are adjunctive therapy — not the other way around,” he said.

But it is cheaper to medicate children than to pay for family counseling, a fact highlighted by a Rutgers University study last year that found children from low-income families, like Kyle, were four times as likely as the privately insured to receive antipsychotic medicines.

Texas Medicaid data obtained by The New York Times showed a record $96 million was spent last year on antipsychotic drugs for teenagers and children — including three unidentified infants who were given the drugs before their first birthdays.

In addition, foster care children seem to be medicated more often, prompting a Senate panel in June to ask the Government Accountability Office to investigate such practices.

In the last few years, doctors’ concerns have led some states, like Florida and California, to put in place restrictions on doctors who want to prescribe antipsychotics for young children, requiring a second opinion or prior approval, especially for those on Medicaid. Some states now report that prescriptions are declining as a result.

A study released in July by 16 state Medicaid medical directors, which once had the working title “Too Many, Too Much, Too Young,” recommended that more states require second opinions, outside consultation or other methods to assure proper prescriptions. The F.D.A. has also strengthened warnings about using some of these drugs in treating children.

No Medical Reason

Kyle was rescued from his medicated state through a therapy program called Early Childhood Supports and Services, established in Louisiana through a confluence of like-minded child psychiatrists at Tulane, Louisiana State University and the state. It surrounds troubled children and their parents with social and mental health support services.

Dr. Mary Margaret Gleason, a professor of pediatrics and child psychiatry at Tulane who treated Kyle from ages 3 to 5 as he was weaned off the heavy medications, said there was no valid medical reason to give antipsychotic drugs to the boy, or virtually any other 2-year-old. “It’s disturbing,” she said.

Dr. Gleason says Kyle’s current status proves he probably never had bipolar disorder, autism or psychosis. His doctors now say Kyle’s tantrums arose from family turmoil and language delays, not any of the diagnoses used to justify antipsychotics.

“I will never, ever let my children be put on these drugs again,” said Ms. Warren, 28, choking back tears. “I didn’t realize what I was doing.”

Dr. Edgardo R. Concepcion, the first child psychiatrist to treat Kyle, said he believed the drugs could help bipolar disorder in little children. “It’s not easy to do this and prescribe this heavy medication,” he said in an interview. “But when they come to me, I have no choice. I have to help this family, this mother. I have no choice.”

Ms. Warren conceded that she resorted to medicating Kyle because she was unprepared for parenthood at age 22, living in difficult circumstances, sometimes distracted. “It was complicated,” she said. “Very tense.”

Behavior Problems

Kyle was a healthy baby physically, but he was afraid of some things. He spent hours lining up toys. When upset, he screamed, threw objects, even hit his head on the wall or floor — not uncommon for toddlers, but frightening.

“I’d bring him to the doctor and the doctor would say, ‘You just need to discipline him,’ ” Ms. Warren said. “How can you discipline a 6-month-old?”

When Kyle’s behavior worsened after his brother was born, Ms. Warren turned to a pediatrician, Dr. Martin J. deGravelle.

“Within five minutes of sitting with him, he looked at me and said, ‘He has autism, there’s no doubt about it,’ ” Ms. Warren said.

Dr. deGravelle’s clinic notes say Kyle was hyperactive, prone to tantrums, spoke only three words and “does not interact well with strangers.”

He prescribed Risperdal. At the time, Risperdal was approved by the F.D.A. only for adults with schizophrenia or acute manic episodes. The following year it was approved for certain children, 5 and older, with autism and extremely aggressive behavior. It has never been approved by the F.D.A. for use in children younger than 5, although doctors may legally prescribe for any use they see fit.

“Kyle at the time was very aggressive and easily agitated, so you try to find medication that can make him more easily controlled, because you can’t reason with an 18-month-old,” Dr. deGravelle said in a telephone interview. But Kyle was not autistic — according to several later evaluations, including one that Dr. deGravelle arranged with a neurologist. Kyle did not have the autistic child’s core deficit of social interaction, Dr. Gleason said. Instead, he craved more positive attention from his mother.

“He had trouble communicating,” Dr. Gleason said. “He didn’t have people to listen to him.”

After the neurologist review, the diagnosis changed to “oppositional defiant disorder” and the Risperdal continued.

“Yes, I did ask for it,” Ms. Warren said. “But I was at my wit’s end, and I didn’t know what else to do.”

Dr. deGravelle referred her to Dr. Concepcion, who in turn diagnosed Kyle’s condition as bipolar disorder.

“Some children, when they come to me, the parents are really so frustrated,” Dr. Concepcion said in a phone interview. “Especially the mothers are so scared or desperate in getting help. Their children are really acting psychotic.”

Dr. Concepcion also spoke with Dr. Charles H. Zeanah, a Tulane medical professor, who disagreed with both the diagnosis and the treatment. “I have never seen a preschool child with bipolar disorder in 30 years as a child psychiatrist specializing in early childhood mental health,” Dr. Zeanah said

More Pills

“It’s a controversial diagnosis, I agree with that,” said Dr. Concepcion. “But if you will commit yourself in giving these children these medicines, you have to have a diagnosis that supports your treatment plan. You can’t just give a nondiagnosis and give them the atypical antipsychotic.”

He also prescribed four more pills.

Kyle’s third birthday photo shows a pink-cheeked boy who had ballooned to 49 pounds. Obesity and diabetes are childhood risks of antipsychotics. Kyle smiles at the camera. He is sedated.

“His shell was there, but he wasn’t there,” Ms. Warren said. “And I didn’t like that.”

Dr. Concepcion referred Kyle to the early childhood support program, which has helped about 3,000 preschoolers from low-income families at risk for mental health problems since 2002.

His speech improved. He threw fewer tantrums. “They started working with us as a family,” said Ms. Warren, who also received parenting advice. “That helps.”

Kyle’s treatment was directed by Dr. Gleason, a Columbia medical graduate who had led a team that wrote 2007 practice guidelines for psychopharmacological treatment of very young children.

“Families sometimes feel the need for a quick fix,” Dr. Gleason said. “That’s often the prescription pad. But I’m concerned that when a child sees someone who prescribes but doesn’t do therapy, they’re closing the door that can make longer-lasting change.”

Off most drugs, Kyle started losing weight and his behavior improved. Ms. Warren’s life also improved. She met a man and they moved into their own house five miles out of Opalousas, a town of 25,000. They were married last Saturday.

At their home recently, Kyle and his brother, Jade, ran and played while their baby sister watched from a playpen. Their clothes were neatly folded in a shared bedroom. They often responded “Yes, ma’am” or “Yes, sir.”

“They’re respectful, but they’re hyper kids,” Ms. Warren said. “Once he came off the medication, he’s Kyle. He’s an intelligent person. He’s loud. He’s funny. He’s smart. He’s bouncy. I mean, there’s never a dull moment. He has a few little behavior issues. But he’s like any other normal 6-year-old.”

Kyle paused to show a reading report card from the end of his kindergarten year, with an A grade.

“Awesome job, Kyle!” his kindergarten teacher wrote.