by Leonard Roy Frank
[dropcap]O[/dropcap]n 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?