Pharmaceutical companies wooed academic leaders, ghostwrote articles, suppressed damaging health data and lavished doctors with gifts to make prescribing powerful psychotropic drugs to children a blockbuster profit center, a trail of lawsuits over the past two decades shows.
As a Colorado Springs sales representative for GlaxoSmithKline, Greg Thorpe tried to put a stop to the practice. His manager wrote him up for not being a “team player” after he objected to the free spa treatments and pedicures, hunting trips, tickets to sports games and skiing junkets that his supervisors expected him to give out to doctors and others.
“The sky was the limit,” said Thorpe, whose whistle-blower lawsuit against his former employer ended with a $3 billion settlement with the federal government. “Those who spent more money got rewarded because they were positioning the company for more business. And it did pay off.”
It was just one part of the massive effort by the pharmaceutical industry to drive sales of antidepressants, antipsychotics and other psychotropic drugs to treat poor children, often for uses never approved by federal regulators.
The push succeeded in reaching a particularly vulnerable group: foster children, who experts say often struggle to cope with trauma that psychotropic drugs don’t heal.
A Denver Post investigation into antipsychotic use found that foster children were prescribed the potent mood-altering drugs at a rate 12 times higher than that of other children on Medicaid in Colorado in 2012. Dosages and rates of multidrug prescriptions also were high among foster children in this state.
Colorado officials knew about rising prescription rates and dosages of psychotropic drugs, which include antipsychotics and antidepressants, as early as 2007 but didn’t convene a panel to address the issue for more than five years.
High rates of psychotropic drug use among poor and foster children didn’t occur by mistake, government investigators say. Court documents filed in health care false-claims lawsuits show that drug companies closely tracked the prescribing habits of doctors in the Medicaid program, which pays the health care of the poor, including foster children.
In Colorado, nine of the top 10 most prescribed drugs for foster children in the Medicaid program are psychotropics, according to the most recently available data. In contrast, for non-foster children, only one psychotropic is among the top 10 most prescribed drugs in Medicaid.
Pharmaceutical companies in 2008 alone spent nearly $800 million on sales representatives making visits to health care professionals for antipsychotics and antidepressants, a December 2009 report from the nonpartisan Congressional Budget Office found.
And that’s not counting additional money paid to health care providers for speeches, consulting and research, some of which went to Colorado doctors.
John T. Hardy, an adolescent and child psychiatrist in Pueblo, received about $400,000 from 2009 through 2011 in travel, consulting and speaking fees and meals from drug companies, including antipsychotic manufacturers Eli Lilly and Pfizer, according to a ProPublica database.
A variety of psychotropic drugs — some simultaneously — are used by many children in the foster-care system. Olanzapine, sold under brand names
A Colorado panel studying the high use of psychotropics among foster children in Colorado reviewed Medicaid drug prescriptions and found that in 2012, Hardy was one of the highest volume prescribers in the state of mental health drugs.
“I do what’s best for my patients,” said Hardy, adding that pharmaceutical money doesn’t influence his prescribing decisions. The number of psychotropic prescriptions Hardy wrote could not be obtained by The Post.
Lucrative drugs
Far from the niche market they originally served, antipsychotics these days are some of the most lucrative drugs, with sales topping $18 billion in 2011, more than sales of vaccines and triple the amount spent on antipsychotics in 2002, national drug-sales data show.
More than 1 million children in America take antipsychotics annually, and tens of thousands of those are younger than 5, a 2009 Food and Drug Administration advisory committee study found.
One in 25 children in the nation between the ages of 12 and 17 took antidepressants in 2011, according to a study by the Centers for Disease Control and Prevention that also found that use of the drugs in Americans of all ages increased by 400 percent in the past two decades.
Pharmaceutical firms say the explosive growth has filled an important need and deny that the growth was driven by inappropriate marketing. Officials with those companies say many more people whose symptoms haven’t yet been addressed and aren’t taking the drugs could benefit from taking antidepressants and anti-psychotics.
But many child health experts warn that the increase comes at a tremendous cost to public health programs and at great risk to children. Antipsychotics have been linked to weight gain and diabetes in children and growth of breasts in boys. The FDA has warned that antidepressants increase suicidal behavior and thinking in children and adolescents.
“We really don’t know enough about the safety and effectiveness of these drugs,” said Dr. Tobias Gerhard, an assistant professor at Rutgers University who has studied the growth in prescribing antipsychotics to children and adolescents.
While antipsychotics’ effectiveness and safety remain hotly debated, the prescription of them has become standard practice for treating children for “off-label” uses that have never been approved by federal regulators.
At least three-quarters of the children prescribed antipsychotics through Medicaid took them for issues beyond FDA-approved uses for the drugs, a Rutgers University study found. The drugs often are prescribed for attention-deficit hyperactivity disorder, conduct disorder, anxiety or depression, none of which is a condition the FDA has approved for treatment by antipsychotics in children, the study found.
“It’s an issue that’s getting a lot of attention, but it’s very difficult for payers to impact the prescribing behaviors of clinicians in America,” said Dr. Stephen Crystal, who led that research team. “Major manufacturers of these drugs have paid fines in the hundreds of millions of dollars for alleged improper marketing, in some cases for use in kids.”
Doctors are free to prescribe drugs for any symptom, even if that results in a drug use that has never been approved by the FDA. But it’s against the law for pharmaceutical firms to encourage doctors to prescribe off-label.
$13 billion paid
Since 2008, pharmaceutical companies have agreed to pay more than $13 billion to resolve U.S. Department of Justice allegations of fraudulent marketing practices. Among the cases:
Eli Lilly distributed videotapes to doctors titled “The Myth of Diabetes” when marketing its antipsychotic Zyprexa, despite being aware of studies showing those taking the drug had a higher rate of diabetes, government investigators say. The government accused the company of pressing doctors to prescribe Zyprexa to children and collected a $1.4 billion fine.
Pfizer, which paid a $2.3 billion fine to settle a whistle-blower lawsuit, hired 250 child psychiatrists to help market its antipsychotic Geodon despite there being no approved pediatric use for the drug from the FDA. As part of the settlement, Pfizer denied any wrongdoing.
AstraZeneca paid a fine of $520 million to resolve allegations that it promoted the antipsychotic Seroquel to treat aggression, sleeplessness, anxiety and depression when the FDA had approved the drug only to treat schizophrenia and, later, bipolar mania. Government investigators said the company targeted child physicians.
Johnson & Johnson targeted what it called key opinion leaders to help promote the use of anti-psychotic Risperdal in children, the government alleged in another lawsuit that resulted in a $2.2 billion fine to resolve criminal and civil allegations.
The GlaxoSmithKline whistle-blower case in which Thorpe was a plaintiff included allegations the company encouraged health care providers to prescribe antidepressants to children when the FDA had not approved the drugs for pediatric use. Glaxo agreed to pay $3 billion to the federal government to settle the case, the largest health care false-claims act settlement ever.
Government investigators found that Glaxo aggressively marketed Paxil off-label as curing everything from depression to shyness in children. Increasing pediatric prescriptions of the drug was a key business strategy for the company, one that helped propel Paxil to $2.7 billion in sales in the United States in 2003, documents show.
Between 1994 and 2001, the company conducted three trials using Paxil to treat depression in those under 18. None of the trials showed the drug helped depressed children, the government asserted. But the trials showed that Paxil had harmful effects and increased the likelihood of suicidal thinking and behavior in children.
Despite those damaging findings, the company hired a firm to help it publish a favorable article about Paxil in the Journal of the American Academy of Child and Adolescent Psychiatry.
It wasn’t until 2006, two years after the FDA ordered all manufacturers of antidepressants to provide cautionary warnings on their labels, that Glaxo changed Paxil’s label to note the suicidal risk and sent letters to doctors alerting them of the risk.
Glaxo officials say the company has made broad changes to its drug-marketing policies. It no longer provides bonuses to sales representatives for increasing prescription volume. Glaxo also has begun publishing all drug-trial results and says it will stop offering to pay doctors to give speeches touting drugs.
Industry trade groups also have adopted new policies restricting the gifts that drug sales representatives can offer physicians.
But Thorpe said the changes come too late. The public still is left struggling with high prescription rates to treat the very young, he said.
“An off-label script is a script that keeps giving whether you stop promoting the drug or not,” he said. “A doctor will keep prescribing the drug if he’s become comfortable with it. The patient likes the drug, so they will want it. It becomes a profit for life.”
Thorpe said he became disgusted with Glaxo’s all-expense-paid trips to Jamaica and Hawaii for physicians and their guests to train them how to give speeches touting the drugs.
Some speakers were paid more than $500,000 annually to talk up the benefits of treating children with antidepressants when the FDA had never approved the drugs for such uses, documents show. The company budgeted as much as $6.8 million annually to entertain doctors in luxury sky-box suites at sporting venues, according to the documents.
Thorpe left the company where he had worked 24 years and later filed his lawsuit. It took nine years for government prosecutors to join the suit.
In 2012, Glaxo agreed to settle. Thorpe’s cut for helping the government recuperate money drained from the Medicare, Medicaid and veteran programs was $20 million.
Off-label uses pushed
Glaxo was not the only company to use such tactics. Other firms pushed for off-label uses of newer antipsychotics, known as atypicals, contending they worked better than older versions.
During the 1990s, Johnson & Johnson received FDA approval for its new antipsychotic drug, Risperdal, to treat schizophrenia in adults. But the agency repeatedly rejected J&J’s efforts to obtain approval for children.
The company had not proposed any child or adolescent psychiatric disorders that Risperdal would treat, the FDA noted in one denial letter. In one meeting, FDA officials worried that using the drug to treat conduct disorder in children would amount to creating a “chemical straitjacket.” It was not until 2006 that FDA officials approved the drug for the limited use of treating autism in children.
Still, the company trained its sales force to market the drug to primary-care doctors and child psychiatrists well before that 2006 approval. More than 1,500 child psychiatrists, targeted due to their antipsychotic prescribing history, each received at least 12 calls from J&J sales representatives in 2000 , documents show.
In 2003, when Risperdal still had no FDA-approved use for children, the company developed a “Back to School Bash.” The marketing plan aimed to increase prescriptions of Risperdal to children and adolescents with ice-cream parties and free snacks and lunches.
One district manager praised a sales representative for promoting a new, faster-dissolving version of Risperdal by providing starter kits to child psychiatrists. The kits included free Risperdal samples, coupons for the drugs, lollipops and small toys, a performance review shows.
Other initiatives that J&J launched for Risperdal created problems for the company.
A research partnership with a prominent child psychiatrist backfired when it was revealed that the psychiatrist and two others had accepted $4.2 million from pharmaceutical companies from 2000 to 2007.
J&J hired a marketing firm to ghostwrite articles attributed to academicians who had done little to no work, according to a report from Dr. David Rothman, a Columbia University professor who studies medical industry ties. Rothman was an expert witness for the Texas Attorney General’s Office in a lawsuit against J&J.
Along the way, the company kept from the public key health data showing troubling risks of Risperdal.
In the pediatric market, the company downplayed the risk that the drug would cause the growth of prolactin in boys, which can cause them to develop lactating breasts, said David Kessler, a former FDA chief who was an expert witness in personal-injury lawsuits filed against Janssen Pharmaceuticals Inc., a J&J subsidiary.
Kessler found the company was responsible for medical-journal articles that gave misleading information about the results of studies into the prolactin issue.
In fact, the company’s studies showed breasts developing in about 10 out of 100 children taking the drug, Kessler reported.
“Janssen’s promotion of Risperdal, a powerful drug, for nonapproved uses in the most vulnerable children is deeply troubling,” Kessler stated in his report.
Janssen officials said those activities are in the past.
“Janssen is committed to ethical business practices and has policies in place to ensure its products are only promoted for their FDA-approved indications,” said spokesman Robyn Reed Frenze. “In fact, the company’s policies meet and often exceed the legal requirements of all jurisdictions it operates within and all local industry codes of which it is a member.”
While the court settlements seem big, they don’t compare to the profits the sales of the drugs generate, said Stephen Sheller, a Philadelphia lawyer who worked with the justice department on a whistle-blower lawsuit involving Risperdal.
J&J generated $4.55 billion in annual sales of Risperdal, 18 percent of its pharmaceutical sales, according to financial reports the company filed with federal regulators in 2008.
Meanwhile, lawsuits against pharmaceutical firms alleging violations of the federal false-claims act continue to be filed at a rapid pace. The justice department says 500 health care fraud act lawsuits were filed last year, the most ever in a year.
“Nothing is going to change significantly until a few top people go to jail,” Sheller said. “There is too much money to gain by marketing the drugs illegally.”
Christopher N. Osher: 303-954-1747, cosher@denverpost.com or twitter.com/chrisosher
