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Zyprexa: A Prescription for Diabetes, Disease and Early Death
by Leonard Roy Frank
There were 20 deaths, including 12 suicides, in the Zyprexa group.
Shockingly, these deaths went unreported in the scientific literature.
The death cover-ups also took place in reporting trial results of
several other atypical antipsychotics. These deaths occurred during very
short trial periods, so the FDA's approval of these drugs is appalling.
On June 8, 2005, Eli Lilly & Co. announced that it had agreed to pay
$690 million to settle some 8,000 lawsuits filed by people who reported
that taking the antipsychotic drug Zyprexa resulted in unwanted weight
gain, diabetes, other metabolic diseases, and death.
Zyprexa, Lilly's top-selling drug, is used in the treatment of
schizophrenia and in the short-term treatment of manic episodes
associated with bipolar disorder. More than 2,500 other claimants
refused to participate in the settlement, presumably in the belief that
the amount received by each claimant, $62,500 on average, was
insufficient compensation for the pain and suffering Zyprexa caused them.
On July 21, Eli Lilly came out with its second-quarter financial report
showing that $1.07 billion was allocated to cover its liabilities in
these lawsuits. That amount exceeded the $690 million settlement by $380
million. The additional sum was the company's estimate of its liability
and defense costs for the unsettled claims [reported in Forbes.com, July
21, 2005]. News of the settlement may generate more damage claims, in
which event the cost to Eli Lilly may be greater than the $1.07 billion
already set aside.
According to Eli Lilly, about 17 million people in 86 countries have
taken Zyprexa since its introduction in 1996. Although there is no way
of accurately estimating the number of Zyprexa's victims, it's safe to
say that this drug has caused diabetes and other diseases in millions of
people, and that tens of thousands of people have died or will die
prematurely.
Despite these facts, the media has paid scant attention to the
settlement. Despite these facts, there hasn't been a single voice of
outrage or protest heard in the halls of Congress or on the evening
news. And despite these facts, Eli Lilly has made no special effort to
warn the public of the potentially disastrous consequences of taking
Zyprexa as it continues to rake in profits from the sale of this drug.
Zyprexa, whose generic name is olanzapine, belongs to a class of
psychiatric drugs known as atypical antipsychotics. Others in this class
are Novartis' Clozaril (clozapine), Janssen's Risperdal (risperidone),
AstraZeneca's Seroquel (quetiapine), Bristol-Myers Squibb's Abilify
(aripiprazole), and Pfizer's Geodon (ziprasidone).
The first atypical antipsychotic, Clozaril, came on the market in 1990.
The manufacturers hailed these drugs as more effective and safer than
the conventional antipsychotics such as Thorazine (chlorpromazine),
Haldol (haloperidol), and Navane (thiothixene), which have been
available since the 1950s.
Following expensive marketing and promotional campaigns by the
manufacturers of the atypicals, belief in their unsubstantiated claims
became widespread, with the result that the companies were able to
charge much more for the newer drugs than were being charged for the
older ones. Today, a month's supply of Zyprexa costs about $380, 10-30
times more expensive than a month's supply of a conventional antipsychotic.
Total worldwide sales for the antipsychotics have grown from less than
$500 million in 1993 (almost all conventional antipsychotics) to more
than $14 billion in 2004 (all but $1 billion of which came from atypical
antipsychotics).
For more than 10 years, the drug companies have consistently downplayed
some of the serious risks associated with taking atypical antipsychotic
drugs. Psychiatrist E. Fuller Torrey, a leading proponent of drug
therapy for schizophrenics, has written about one of the techniques used
to mislead physicians and the public: "Psychiatrists trying to evaluate
schizophrenia drugs are not told that the expert who minimizes the side
effects of Zyprexa receives a $10,000 retainer from Eli Lilly and also
owns substantial company stock." [American Prospect, July 15, 2002]
Faced with mounting evidence of their harmfulness, the Food and Drug
Administration (FDA) finally required, in 2003, all manufacturers of the
atypicals to place on their labels a warning about the increased risk of
diabetes for users of these drugs.
Hersh and Hersh, a San Francisco law firm representing some 400 of the
claimants in the recent settlement, charged that Eli Lilly "fraudulently
withheld relevant information from potential users of Zyprexa" before
2003. Eli Lilly, went the charge, failed to warn doctors and patients
that Zyprexa carried terrible and potentially lethal risks from weight
gain and diabetes, which the company knew or should have known.
Such warnings might have led doctors to lower dosage levels in
prescribing Zyprexa and to regularly test the blood-sugar levels of
their Zyprexa patients. They might even have caused some doctors to stop
prescribing the drug.
With these precautions, there undoubtedly would have been fewer cases of
diabetes and fewer deaths from taking Zyprexa. But truthfulness is not
one of Eli Lilly's strong suits when profits are at stake. Telling the
truth about Zyprexa would undoubtedly have cut into sales for its
blockbuster drug (the fifth best-selling prescription drug in the
world), which, in 2004, produced revenues of $4.4 billion, almost a
third of the company's total revenues and more than a third of its profits.
The drug is of paramount importance to Eli Lilly's bottom line. The
company seems to have developed a Zyprexa addiction, from which
withdrawal will be difficult. Eli Lilly has also realized indirect
profits from Zyprexa sales. It's a cruel irony that while the company is
filling its coffers by selling a drug that can cause diabetes, four of
its top-selling drugs are treatments for diabetes, with Humulin and
Humalog each expected to top $1 billion in annual revenues. Eli Lilly
gets the customer coming and going.
Potential and current users of the drug, doctors, and the public are
still almost totally in the dark about Zyprexa's shameful history. Based
on the results of a six-week clinical trial sponsored by Eli Lilly, the
FDA granted the company permission to manufacture and distribute Zyprexa
on September 27, 1996. The trial involved 2,500 subjects, and two-thirds
of them didn't even successfully complete the trial. Among those who
stuck it out, 22 percent of the Zyprexa subjects suffered a "serious"
adverse effect, compared to 18 percent in the group taking Haldol.
The FDA reviewers found there was an average weight gain of almost one
pound a week during the six-week trial period and 26 pounds over a
year-long period for the Zyprexa subjects who remained for the extension
trial. Other drug effects included shaking, spasms, sedation, diabetic
complications, rapid heartbeat, restlessness, constipation, seizures,
liver problems, white blood cell disorders, and decreased blood pressure.
In addition, there were 20 deaths, including 12 suicides, in the Zyprexa
group. Shockingly, these deaths went unreported in the scientific
literature. The death cover-ups also took place in reporting trial
results of several other atypicals during the 1990s.
Information concerning these deaths was obtained from FDA documents
through the Freedom of Information Act by science writer Robert
Whitaker, who wrote that one in every 145 subjects who entered the
trials for Zyprexa, Risperdal, Seroquel, and Serdolect had died. [See
Mad in America: Bad Science, Bad Medicine, and the Enduring Mistreatment
of the Mentally Ill, by Robert Whitaker.]
Bearing in mind these deaths, which occurred during very short trial
periods, the FDA's approval of three of the four atypicals cited above
(Serdolect was unapproved) is appalling. It not only condemns the
agency's approval process but also raises doubts about the agency's
political independence.
In the case of Zyprexa, Eli Lilly's ties to the two Bush administrations
are a matter of public record. President George H. W. Bush is a former
member of Eli Lilly's board of directors. In 2000, Eli Lilly made
campaign contributions of $1.6 million, 82 percent of which went to
President George W. Bush and other Republicans. In 2001, President Bush
appointed Mitch Daniel, a former Eli Lilly vice president, to be White
House director of the Office of Management and Budget. And in 2002,
President Bush appointed Sidney Taurel, Eli Lilly's current chairman and
CEO, to the Homeland Security Council.
The failure to report the deaths in the reviews of FDA atypical trials
published in the professional literature, which psychiatrists and other
doctors rely on for guidance in their prescription practices, unmasks
the duplicity of the companies involved, the psychiatrists who
collaborated with them by writing the articles, and the journal editors
who accepted their articles for publication.
In recent years, some reports of death from the atypicals have appeared
in the media, most often one-shot affairs in a few newspapers with
little or no follow-up. These deaths were usually associated with weight
gain and/or diabetes.
For example, in February 2001, Frank Olenick, a Winterville, Ohio, truck
driver, died after going into a diabetic coma at age 40. His widow
Christine Olenick's lawsuit against Eli Lilly said that he began taking
Zyprexa to treat depression and withdrawal symptoms from a painkiller
prescribed for a job-related injury. Two months later, she rushed her
sick husband to a hospital, where a nurse told her his blood-sugar level
was 15 times higher than normal, although he hadn't had diabetes. Mrs.
Olenick said he went into a coma an hour later and died. [Indianapolis
Star, March 16, 2003]
In another case, Rob Liversidge, 39, of Silver Spring, Maryland, gained
more than 100 pounds while taking Zyprexa for manic-depression. Health
problems related to this weight gain ended his government career. A week
before he was to start a new job following a long layoff, Liversidge
collapsed and was taken to a hospital where, despite emergency
treatment, he went into a coma and died four days later. [Baltimore Sun,
March 19, 2003]
Those two cases made it to the newspapers. But the large majority of
complications and deaths from Zyprexa are hidden from public view and
may not even be recognized as such. An exception was P. Murali
Doraiswamy's review of complications among Zyprexa users voluntarily
reported to the FDA over a six-year period.
Doraiswamy, the chief of biological psychiatry at Duke University,
wrote: "Of the 289 cases of diabetes linked to the use of [Zyprexa], 225
were newly diagnosed cases. One hundred patients developed ketosis (a
serious complication of diabetes), and 22 people developed pancreatitis,
or inflammation of the pancreas, which is a life-threatening condition.
There were 23 deaths, including that of a 15-year-old adolescent who
died of necrotizing pancreatitis, a condition where the pancreas breaks
down and dies. Most cases (71 percent) occurred within six months of
starting the drug and many cases were associated with moderate weight
gain." [Pharmacotherapy, July 2002]
There is also an added risk of death for elderly people with dementia
taking Zyprexa and other atypicals. In early 2005, the FDA analyzed the
results of 17 placebo-controlled trials involving the atypicals,
including Zyprexa. The agency found that older patients with dementia
who were given the pills were 1.6 to 1.7 times more likely to die,
mostly from heart-related problems like heart failure or infections like
pneumonia, as those given placebos.
Based on this review, the FDA now requires the makers of these drugs to
place black-box warnings for elderly patients with dementia on labels
for the atypicals. Black-box warnings are reserved for drugs posing the
greatest health risks. [New York Times, April 12, 2005]
But there is no black-box warning for children and adolescents being
prescribed Zyprexa, and doctors apparently are prescribing the drug to
growing numbers of youngsters. The drug has not been FDA-approved for
any childhood condition; but doctors have been prescribing Zyprexa and
other atypicals for autism, attention deficit disorder, hyperactivity,
withdrawal, and aggression. Children in foster homes are especially
vulnerable to this kind of abuse.
Weight gain may be the most troubling effect of Zyprexa because it, in
turn, causes many other problems. The weight-gain issue should not be
minimized as was done by Dr. Alan Breier, Eli Lilly's vice president of
pharmaceutical sales and head of the Zyprexa product team, who told the
Indianapolis Star on April 16, 2003, that Zyprexa, like some of the
other antipsychotic drugs, causes weight gain in about half of all
users. Excessive weight gain would have been a more accurate way of
putting it.
Practically everyone taking Zyprexa gains at least some weight
attributable to the drug. Breier also said that while weight gain is a
risk factor for diabetes, it doesn't of itself necessarily lead to
diabetes. Sure, and smoking doesn't of itself necessarily lead to lung
cancer. Extreme weight gain can result in obesity, which in recent years
has reached near-epidemic proportions in the United States. Obesity
further increases the risk of diabetes. There are now 18 million
diabetics in this country. With more than half a million current users,
Zyprexa is worsening an already critical situation.
The obesity problem is illustrated in the following excerpt from Sharon
Begley's Newsweek article on March 11, 2002, in some ways favorable to
Zyprexa, which broadly describes the drug's effects: "Although the
voices and visions don't always disappear, the new drugs [i.e., the
atypicals] can allow people with schizophrenia to hold jobs and have
families. Still, they increase appetite, and may alter metabolism,
resulting in what [Richard Wyatt, chief of neuropsychiatry at the
National Institute of Mental Health] calls 'the enormous problem' of
huge weight gain. [Donna Willey, a patient interviewed for the article]
gains 20 pounds a year on Zyprexa, and has ballooned from 120 pounds to
her current 280. That makes some reluctant to take the drugs. Another
side effect is foggy thinking, the feeling that brain signals are trying
to push through caramel. Patients may also lose their libido. For all
the power of the new drugs, they are treatment and not cure."
Lives diminished, lives shortened, lives destroyed! All this misery and
suffering, and for what advantage? One review of 52 studies involving
12,649 patients concluded, "There is no clear evidence that the atypical
antipsychotics are more effective or better tolerated than conventional
antipsychotics." [John Geddes et al., British Journal of Psychiatry,
December, 2000]
Eli Lilly executives, however, take no responsibility for the harm
they've caused. They've made no apology. There's been no contrition.
There's only been denial. Eli Lilly CEO Sidney Taurel has said of the
legal settlement: "While we believe the claims are without merit, we
took this difficult step because we believe it is in the best interest
of the company, the patients who depend on this medication, and their
doctors. We wanted to reduce significant uncertainties involved in
litigating such complex cases."
These were not off-the-cuff remarks; they were included in Eli Lilly's
press release on the settlement. Such a response would be laughable were
the issues less serious for the public and for Eli Lilly shareholders.
One can only imagine what these shareholders think about a chief
executive who authorized the payment of $690 million in damages for
claims that were, in his opinion, "without merit."
But given Zyprexa's profitability, Eli Lilly shareholders may have
little to complain about. The expense is just a cost of doing business.
Besides, what's a charge of $690 million, or even $1.07 billion, against
profits of many billions that Lilly has made from Zyprexa since its
introduction nine years ago, to say nothing of the future profits it can
be expected to earn?
How have recent developments in the legal arena affected Zyprexa sales
and the price of Eli Lilly's stock? Worldwide Zyprexa sales fell 10
percent in the second quarter of 2005 compared with the same period in
2004; while in the United States, Zyprexa sales for like periods dropped
21 percent. More important, at least in terms of the shareholders'
immediate interests, Eli Lilly's stock has declined roughly 16 percent
from a high of $67.30 during the last 12 months to its current price at
the end of July, of $56.32.
Because of Enron's fraudulent accounting practices, many people lost
their savings. Because of fraudulent drug-information from Eli Lilly,
many more people lost their health or their lives. But unlike the Enron
scandal, none of the responsible parties at Eli Lilly has been sent to
prison or even been charged with a crime. Bringing Eli Lilly executives
to justice is not likely to happen anytime soon.
Meanwhile, what is to be done? Call it a crime; call it a tragedy; it's
surely a public-safety problem of vast proportions, one demanding
government intervention. Warning people who take or might take Zyprexa
about its grave risks is not a sufficient safeguard.
When, in the early 1960s, the drug thalidomide was shown to cause
horrible deformities in the newborns of thousands of women, the FDA
banned it. Is death a less disastrous drug effect than deformity? How
many more people will have to die before the government steps in to
protect citizens by prohibiting the sale of Zyprexa?
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