Evelyn Pringle September 28, 2006
Scores of new lawsuits are being filed by patients who say they took Zyprexa without knowing the risks after Eli Lilly promoted the drug to doctors as a treatment for conditions other than schizophrenia and bipolar disorder that the drug is approved to treat.
In June 2005, Lilly announced plans to settle roughly 8,000 claims by patients alleging the development of diabetes due to the use of Zyprexa. In an unusually early settlement, Lilly settled the cases for $690 million after only five plaintiffs had provided depositions and before any substantive depositions had been taken from the Lilly defendants.
However, it appears that no amount of lawsuits are going to deter Lilly from promoting the off-label sales of Zyprexa. According to Lilly's latest SEC filing, sales of Zyprexa in the second quarter of 2006 totaled $1.12 billion, a 2% increase over the second quarter of 2005.
Lilly noted in the filing that US sales fell 1% due to a lower demand, but said the company made up for the lower sales by charging a higher price for the drug.
Zyprexa has been approved for treatment of adults with a limited number of conditions. However, although a drug can only be marketed for specific indications approved by the FDA, federal law allows doctors to prescribe a drug for any use regardless of whether its approved for that indication or not.
This loophole has led to Zyprexa being prescribed to treat disorders for which the drug is not approved and for mild psychological disorders for which the drug was never intended.
Critics say this policy must be changed in order to prevent serious health problems in patients who believe the drugs they take are approved and safe merely because a doctor has prescribed them.
Legal experts say it will not take a legal genius to get juries to understand the simple logic that Zyprexa sales would be down, not rising, if Lilly had indeed stopped over-promoting the drug for off-label uses.
Thousands of new lawsuit have been filed since last year's settlement of the first batch of claims. According to Bloomberg News on April 20, 2006, as many as 5,000 new suits have been filed in state and federal courts and more are expected, say attorneys for patients in California, Pennsylvania, Mississippi and Texas.
Patrick Mulligan, a Dallas personal-injury attorney, told Bloomberg that he filed 2,500 Zyprexa suits in state courts after the settlement, primarily in California and Indiana.
And a Zyprexa case filed in Texarkana, Texas, in March 2006, by another law firm involves 492 individuals.
But yet critics say the off-label prescribing continues. "Doctors are prescribing it for women with post-partum depression; they're prescribing it for children who are acting out," said Tommy Fibich, a Houston attorney representing 300 patients to Bloomberg News.
The allegations involving children could be more costly to resolve, according to Robert Rabin, a Stanford University law professor who specializes in product-defect litigation. "Kids are a particularly vulnerable group of plaintiffs," Mr Rabin told Bloomberg.
If the claims involving children can be proven, the damages would be higher, he says, because they would need to be paid over a longer period of time
According to Dr Stefan Kruszewski, MD, a Harvard trained, board certified psychiatrist in adult, adolescent, geriatric and addiction psychiatry, from Harrisburg, Pennsylvania, the new antipsychotics increase the risk of obesity, diabetes type II, hypertension, cardiovascular complications, heart attacks and stroke.
Like most other critics, he also says that Lilly knew about these side effects long before the drug company issued any warnings to doctors and consumers.
"Zyprexa and its antipsychotics counterparts," Dr Kruszewski explains, "were marketed to be safer and easier to tolerate than the older, cheaper antipsychotics because the pharmaceutical companies said that the newer drugs caused fewer neurological injuries, like restlessness or 'akathesia,' and tardive dyskinesia."
Those claims have turned out to be totally false he says. "So, what we have now is a drug, Zyprexa, whose massive revenues and promotion are based upon faulty disclosures by the manufacturer, Eli Lilly," he advises.
"The drug causes both a severe metabolic syndrome consisting of obesity, diabetes and cardiovascular problems," he explains, "at the same time that it continues to cause neurological side-effects like the older antipsychotics."
It does have a major advantage for Lilly, he points out, because a dose of older antipsychotic haloperidol might sell for 6 pennies while a dose of Zyprexa might sell for over 6 dollars.
Using fraud, kickback and antitrust statutes, state attorneys general have filed legal actions against Lilly to recover the money paid out for Zyprexa by government funded programs like Medicaid.
According to the October 23, 2005, San Francisco Chronicle, "Nationwide, Medicaid programs purchase an estimated 60 to 75 percent of antipsychotic drugs."
Zyprexa holds the title of top money maker for Lilly when it comes to state funded healthcare programs. For instance, Zyprexa was the highest expenditure for Medi-Cal, California's version of Medicaid, at close to $250 million in the year ending in June 2005.
Private health care programs also want their money back. A lawsuit filed in New York in August 2004, on behalf of private health insurers accuses Lilly of violating racketeering laws, in part, by bankrolling nonprofit groups to promote Zyprexa as a treatment for a number of unapproved conditions and to downplay the medicine's side effects.
Proof of this allegation can be found in Kentucky. In 2002, the Kentucky Medicaid program had a $230 million deficit, and a $36 million bill for Zyprexa was the largest drug expense.
When Kentucky held public hearings and tried to exclude Zyprexa from Medicaid's list of preferred drugs, the most notorious pharma front group in the US, the National Alliance for the Mentally Ill (NAMI), bused in protesters to the hearings, placed full-page ads in newspapers, and sent faxes to state officials. However, what NAMI did not reveal at the time was that the buses, ads, and faxes were paid for by Eli Lilly, according to the December 18, 2003 New York Times.
NAMI also came out in full force to discredit a study by the National Institute of Mental Health, the largest and longest independent study on the new antipsychotics to date, called the Clinical Antipsychotic Trials of Intervention Effectiveness, or CATIE. The results of the study released in September 2005, said the new atypical antipsychotics "have no substantial advantage" over the old ones.
The minute the CATIE results were made public, the NAMI army was disbursed to protect the profits of the new drugs. First, NAMI blamed the results of the study on patients who participated. Many patients dropped out or discontinued the medication, NAMI said, because they suffered from a co-occurring disorder called anosognosia, or "lack of insight" into the need for treatment.
Next it complained about the fact that the CATIE study "only lasted for 18 months," although critics point out that NAMI has never been heard to complain when a drug company trial lasted a mere 12 weeks or less.
It in fact, critics say, it will not be difficult to prove that all the major drug companies pay big money to these front groups to do their bidding. For instance, in a March 9, 2005, Press Release, the Health and Social Campaigners' Network International, revealed a survey of annual reports from "patient advocacy groups" that showed an escalation in pharma donations, but for market-driven reasons.
The survey looked at the top 12 donors (Pfizer; GSK; AstraZeneca; Johnson & Johnson; Merck; Novartis; Aventis; Roche; Lilly; Bristol-Myers; Wyeth; and Abbott), plus the types of health-based charities to which the companies gave their money and found that in almost 100% of cases, the drug makers gave money to the groups that specialize in the therapeutic areas in which the drug companies research, develop or market products.
Overall, the report said, pharma funding can account for more than half of the revenue received by these groups, and yet only four of the 125 annual reports contained information about the specific amounts of money provided by drug companies.
"Not surprisingly, the report noted, "these details were almost entirely absent from most of the reports."
Another lawsuit filed by the attorney general of Mississippi in July 2006, charges that Lilly knew Zyprexa increased the risk of diabetes, pointing out that in April, 2002, nearly a year and a half before Lilly first warned doctors and consumers of the risk of diabetes in the US, the company changed the drug's labeling in the UK and Japan to include warnings about the association between Zyprexa and diabetes related injuries.
According to the attorney general's office, about 10% of Zyprexa patients have developed insulin-dependent diabetes. Some of these patients are children, the lawsuit says, even though Zyprexa "has never been approved for, nor found to be effective, in the treatment of children."
Nonetheless, Lilly has doctors prescribing Medicaid funded Zyprexa to kids all over the country. For instance, a study in the August 3, 2004 Archives of Pediatric Adolescent Medicine, found the number of children in Tennessee covered by the state's TennCare program, who were prescribed antipsychotics nearly doubled in six years. The largest increases were among children aged 13 to 18 at 116%, followed by a 93% increase in children aged 6 to 12. The study also found a 61% increase in use with preschool children.
In Texas, a review of prescriptions for the months of July and August 2004, found that more than 19,400 teenagers were prescribed an antipsychotic billed to a publicly funded program, according to ACS-Heritage, a medical consulting firm hired by the state to investigate the use of psychotropic drugs on children.
Nearly 98% of the teens, ACS said, were prescribed antipsychotics "off-label" for conditions not approved and in more than half of the cases, the dosage appeared to be inappropriately high.
The study also said that almost half of the children did not appear to have a valid diagnosis warranting the use of the drug, and one-third of the children were on 2 or more drugs.
Experts point out that Zyprexa is not only dangerous to use with children, the drug has been shown to be less effective in treating children than the older cheaper class of antipsychotics. The results of a study published in August 2006, by the New York Psychiatric Institute, found that the older antipsychotics worked much better with kids.
According to the study, the average response rate in children among 8 studies employing the new antipsychotics was only 55.7%, compared to a 72.3% response rate among children in 13 studies who were given the older drugs.
In February 2006, Alaska and West Virginia filed lawsuits against Lilly alleging the company improperly marketed the drug for unapproved uses and cost the states millions of dollars after patients developed diabetes and other diseases.
West Virginia is seeking payment for all medical costs related to Zyprexa, in addition to reimbursement for the more than $70 million the state paid for the drug. The state maintains that damages can be tripled under the law cited in the complaint.
The lawsuit says studies have linked Zyprexa to diabetes since 1998, and that sales representatives misled and deceived doctors about the safety and the efficacy of Zyprexa and that Lilly's advertisements deceptively understated risks and overstated benefits.
The complaint alleges that Lilly promoted "off label" prescriptions for a host of conditions including anxiety, sleep disruption, mood swings, attention deficit hyperactivity and dementia. As a result of these actions, the complaint says, Lilly sold more Zyprexa than it would have sold if it had disclosed the risk of diabetes and other diseases.
"Lilly benefited from its misrepresentations and fraudulent conduct by gaining sales of Zyprexa at the expense of other, safe, effective drugs," the complaint states.
Two additional federal class actions were filed against Lilly on February 28, 2006 in New York. One asks for reimbursement for all money paid by consumers and non-government health plans and the other demands medical monitoring of all people who took Zyprexa who have not yet been diagnosed with diabetes, pancreatitis or high blood sugar.
There is no doubt that both the FDA and Lilly knew about these risks long before they alerted doctors and consumers. In a study published in the July 2002 journal Pharmacotherapy, P Murali Doraiswamy, the chief of biological psychiatry at Duke University, reviewed the FDA adverse event reports submitted on Zyprexa patients and found that of the 289 cases of diabetes, 225 patients were newly diagnosed.
In addition, the review showed that 100 patients developed ketosis, a serious complication of diabetes, and 22 people developed pancreatitis, or inflammation of the pancreas that is life-threatening. There were also 23 deaths, including a 15-year-old patient who died of necrotizing pancreatitis.
Lilly has also been hit with Zyprexa lawsuits in Canada. According to company's latest SEC filing, in 2005 the drug maker was served with four lawsuits seeking class action status in Canada on behalf of patients who took Zyprexa, and one of the lawsuits has been certified for residents of Quebec.
"The allegations in the Canadian actions," the filing states, "are similar to those in the litigation pending in the United States."
Also in Canada, according to an August 30, 2006 article in Monday, Victoria health researcher Janet Currie, is calling for a public inquiry into the use of the atypical antipsychotic drugs. The drugs are being prescribed for the wrong reasons to seniors and children, says Ms Currie, the director of the Victoria-based Psychiatric Medication Awareness Group.
"Atypical anti-psychotics are only supposed to be prescribed for schizophrenia and psychosis," she states. "Yet they're being used for sedation and behaviour control."
Ms Currie says she is "absolutely" sure that Zyprexa is being given to children and seniors when it should not be. "It's being prescribed way, way beyond the indicated uses of schizophrenia and psychosis," she says.
Zyprexa is covered by the government funded PharmaCare program. According to BC health ministry data, PharmaCare paid $26,493,119 in 2005 for Zyprexa, $11,688,886 for risperidone (which is sold as Risperdal), and $13,279,737 for quetiapine fumarate (sold under the name Seroquel).
Ms Currie says those figures suggest the drugs are being over prescribed particularly in light of serious side-effects they cause. She reported that one woman had gained more than 100 pounds. "Weight gain exposes you to all sorts of other problems," she says.
According to the Monday article, a special authority drug is one that may only be prescribed under special criteria. In the case of Zyprexa, the patient must have been diagnosed with schizophrenia or other non-dementia-related psychosis and other antipsychotic drugs must have failed, or not been tolerated by the patient.
Ms Currie claims that PharmaCare's controls on "special authority" drugs like Zyprexa are "useless."
"It has no teeth in it at all," she says. "It's not working."
She claims that drug companies are only interested is profits. "They don't care about the damage that may lie in their wake, to individuals, to the family and to the health care system," she says. "It's like a mining company that comes in, rips up a mountain and then walks off."