Washington, DCThe promotion and sale of two classes of psychiatric drugs, the atypical antipsychotics and selective serotonin reuptake inhibitors antidepressants (SSRIs), will go down in history as the most successful off-label marketing scheme of all time.
But unfortunately, before the illegal scheme takes its rightful place in the law books, a lot more deaths and injuries will be left in its wake.
The SSRIs are sold in the US under the names Paxil, by GlaxoSmithKline; Zoloft, from Pfizer; Prozac by Eli Lilly; Celexa and Lexapro, from Forest Laboratories; and Luvox, from Solvay.
On November 7, 2005, Medical News reported that sales of SSRIs topped $10 billion a year. For some companies, the SSRIs are their best sellers. For instance, according to Forest Lab's Annual Report for the year ending March 31, 2006, its two SSRIs, Lexapro and Celexa, accounted for 68% of the company's total sales for the year.
In 2004, SSRIs and antipsychotics became the third and fourth best selling classes of drugs in the country, with sales of $20.7 billion, according to the July 27, 2005 Wall Street Journal.
The atypicals antipsychotics include Eli Lilly's Zyprexa; AstraZeneca's Seroquel; Bristol-Myers Squibb's Abilify; Johnson & Johnson's Risperdal; and Pfizer's Geodon.
According drug company SEC filings for the third quarter of 2005, the atypicals are still top money makers. For the 3 month period, sales of Risperdal reached $916 million, up 23%; Seroquel sales were $706 million, up 32%; Abilify reached $206 million, up 58%; Geodon had sales of $148 million, up 18%; and Zyprexa had sales of more than $1 billion.
Tax payers are the largest contributors to the off-label profits made from the atypicals. On October 23, 2005, the San Francisco Chronicle reported that "Nationwide, Medicaid programs purchase an estimated 60 to 75 percent of antipsychotic drugs."
In California, for instance, the highest Medicaid expense was for Zyprexa, at close to $250 million in the year ending June 2005. The atypicals accounted for four of the top 10 most expensive drugs in the 12 months prior to June 30, 2005, with California spending a combined total of over $620 million on the drugs.
The off-label marketing of these medications includes prescribing a drug for a different illness, or at a different dose, or with a different combination of other drugs, or for a different patient population than those approved by the FDA.
Its illegal for drug companies to promote drugs for uses that have not been approved but its common knowledge that they do it, and get away with it, continuously. But nowhere in the history of the FDA's regulation of the pharmaceutical industry has the off-label sale of specific medications been more blatant than with these two classes of psychiatric drugs.
Atypical antipsychotics were originally approved for the very limited use by adults with schizophrenia and other psychotic disorders, and SSRIs were approved for treating depression in adults.
However, these drugs are now prescribed off-label to teens, children, infants and toddlers, the elderly, and pregnant women, on a regular basis for everything from pain, insomnia, anxiety, shyness, menstrual discomfort, dementia, restless leg syndrome, to scores of other disorders that have been invented and promoted by PR firms and industry backed front groups over the last 15 years.
Most consumers are unaware that doctors in every field of medicine are prescribing drugs that have not been FDA approved as safe and effective for treating all these disorders and conditions.
An analysis of Florida Medicaid data from September 2002 to September 2003, by the Florida Department of Children & Family Services, found that 41,993 children, 12 and under, were given 190,210 off-label prescriptions for psychiatric drugs by doctors in fields that included anesthesiology, dermatology, geriatrics, allergy, nutrition, ophthalmology, obstetrics, pathology, otolaryngology, hematology, diabetes, plastic surgery, radiology, rheumatology and hand surgery.
People often ask how it is that doctors who specialize in these various fields of medicine would even think to prescribe psychiatric drugs off-label to begin with and critics are quick to point out that all roads of encouragement lead straight back to Big Pharma and the prescribing often begins because free samples of a drug are handy.
For instance, Milton Cole, a 71-year-old man in good health, went to a heart doctor complaining of chest pains. When tests did not reveal a problem, the doctor gave him free samples of Prozac, supposedly to blunt the chest pain, according to the November 3, 2003 Miami Herald.
Thirteen days later, Mr Cole's wife found her husband hanging from a beam in a back room of their shop.
His doctor told the Herald that he did not think Mr Cole was depressed. In fact, by all accounts, Mr Cole was upbeat, busy with friends and church, preparing for a new grandchild and a new house.
The doctor said physicians had prescribed antidepressants off-label for years to manage chronic pain, and that as far as he knew, Prozac did not have any serious side effects and he had never heard that it might cause suicide.
"I chose Prozac probably because I had samples of it," he said in the interview with the Herald. "I thought it was a pretty harmless thing to do."
"That a heart specialist even had free supplies of a drug that's usually the province of psychiatrists," the Herald notes, "says a lot about how drug marketing today encourages physicians to prescribe medications for unapproved, or off-label, uses."
"By offering specialty drugs to non-specialists, sending salesmen to doctors' offices and medical conventions, and touting their drugs' benefits on the slimmest of evidence, pharmaceutical companies have sent off-label retail sales soaring," the Herald reported.
At a hearing titled, Overmedication of Hyperactive Children, before the Committee on Government Reform, on September 26, 2002, the chairman said the committee had reports that psychiatric drugs were being prescribed for 2-year-olds on Medicaid and asked Dr Mary Ann Block, author of, "No More ADHD," whether she had any idea how physicians are influenced by the drug companies to prescribe drugs to kids.
"Yes, as a physician, I see this influence all the time," she told the panel.
"For one thing," she said, "I don't think any of us can turn on the television, radio, open up a newspaper or magazine without seeing multiple advertisements for prescription drugs."
"They go so far as to say, "Ask your doctor if this drug is right for you," she continued, "encouraging the public to go to the doctor to get a drug."
"But in addition," she noted, "I don't believe the public is aware of the strong influence the pharmaceutical industry has on physicians."
"From the time we start medical school until the day we start our practice," Dr Block explained, "we are strongly influenced or attempted to be strongly influenced by the pharmaceutical industry."
"Our medical journals," she said, "which are purported to be unbiased, usually have about 60 percent of their pages as full-page ads from the pharmaceutical industry."
"If I go to a continuing medical education meeting," she noted, "the doctors who are talking to us are being paid by the pharmaceutical industry to give those lectures."
"Many doctors are being paid in their offices to do research for the pharmaceutical industries as well," Dr Block told he panel.
"They also give money to different groups who go out and promote the use of these drugs for our children," she noted.
"So the pharmaceutical companies have a tremendous influence on our society and especially on physicians," she said.
Critics say prescribing doctors are greatly influenced by drug sales representatives who provide them with free meals and other perks, along with the free drug samples and the skewed information from industry funded research.
As part of the overall off-label marketing scheme of these psychiatric drugs, Big Pharma pays researchers to conduct studies on the drugs to come up with new uses to widen the customer net, and critics say the drug makers have this method of promoting off-label use down to a science.
First, the results of an industry funded study are published in a reputable medical journal, most often ghost-written by the drug maker or a PR firm, and then doctors who read the journal begin prescribing the drug for the new off-label use described.
And to cover all bases, the drug company feeds the journals money by purchasing thousands of copies of the study for sales representatives to distribute to all prescribing doctors to catch those who might not read the journals.
As part of this particular scheme to market the new psychiatric drugs, Big Pharma also funneled money to key state officials to make sure their new drugs would be included on the state formulary lists so they would be paid for by public health care programs.
For example, Allan Jones, a former fraud investigator in Pennsylvania, discovered a hidden slush fund account in Pennsylvania where drug companies were depositing money that was being accessed by state employees.
"They were given unrestricted educational grants," he explains, "that were deposited into an off-the-books account, unregistered, unmonitored, literally operated out of a drawer."
Mr Jones also discovered that drug makers were paying state employees directly and giving them perks such as lavish meals, trips and honorariums of up to $2,000 to speak in their official capacity at drug company events.
"It is illegal for a public employee to accept honorariums and to consult with industry without permission," he said, "yet it was happening openly."
After the new drugs were added to the state formulary list, according to Mr Jones, in 2003, Pennsylvania spent a combined total of $139 million for SSRIs and atypicals alone.
Contrary to public pretenses portrayed by the industry backed officials at the top of the FDA, the agency is well aware that SSRIs are dangerous and do not work in treating children. On September 28, 2004, according to the Associated Press, Dr Norm Fost, a member of the FDA's Pediatric Ethics Subcommittee at the time, said, "In 23 studies, none of them has been shown to have any efficacy in children, other than Prozac."
"And there's all this increasing noise level about toxicity," he added.
However, those comments represent a rare slip of the tongue because these days, the Bush administration makes sure that very few negative statements to the media about Big Pharma come from the FDA.
In fact, many reporters say that editors are too inclined to defer to the FDA, "which makes it hard for them to write negatively about a drug that has the agency's approval, or to investigate the agency itself," according to Trudy Lieberman in Bitter Pill, in the July-August 2005, Columbia Journalism Review.
She says veteran journalist, "Donald Barlett has observed that there is much more investigative reporting going on today than ever before, but stories that appear once or twice a year do not reverse the damage done by the parade of daily stories that fail to give readers and viewers balanced and in-depth information about their medicines."
Critics say reporters are also fed disinformation about drugs. "The media are victims of the same problem as doctors and patients," Dr Jerry Avorn, a professor of medicine at the Harvard Medical School, told Ms Lieberman.
"Too often," he said, "they get industry-sponsored sources of information that look like they are from unbiased, scientifically driven public-interest groups when in fact they are thickly veiled marketing activities."