Rob Liversidge had reason to hope he was on the long road back from the severe mental illness that had derailed his life.
Aided by a powerful anti-psychotic medication, the 39-year-old Silver Spring man planned to resume the government career that his bipolar disorder had interrupted.
But in October, a week before he was to start a new job, Liversidge collapsed and was rushed to a local hospital. Despite doctors' efforts, he went into a coma and died four days later.
"It was like he never had a chance," says his mother, Ellen Liversidge. Her grief about her son's mysterious death turned to anger, however, when she learned that at least 23 other people had died, and hundreds more suffered potentially life-threatening illness, while taking the same medication.
Zyprexa, widely prescribed to treat bipolar disorder and schizophrenia, has been linked in multiple studies in this country and abroad with diabetes and severe hyperglycemia, a related failure of the body's ability to process sugar. It can quickly lead to coma and death if not discovered and treated soon enough.
Those studies, and actions taken recently by drug regulators in other countries, have prompted some U.S. physicians to call for more prominent warnings to doctors and the public about the potentially life-threatening side effects of this otherwise helpful medication.
"It's clear this is not rare," says Dr. E. Fuller Torrey, director of the Stanley Medical Research Institute in Bethesda, which studies the causes and cures of schizophrenia. "How common it is is not clear yet, but it's very serious."
Torrey contends that the Food and Drug Administration, which regulates the safety of medications, should require a "black-box" warning - with the text in bold type - on Zyprexa's label about the risks of hyperglycemia and diabetes. "There's almost no one who's aware of it out there," he said. "You may be getting deaths of individuals, but no one is putting it together."
An FDA spokeswoman said the agency is reviewing the reports of illness and death, but declined to provide details.
"FDA is evaluating all this information, and we'll make a determination if action is needed," said Susan Cruzan, the spokeswoman. She said regulators are looking at the potential side effects of all anti-psychotic drugs, not just Zyprexa.
The consumer group Public Citizen is considering whether to ask the FDA to require a more prominent label warning for Zyprexa and one or more other anti-psychotic medications that seem to have similar side effects.
"This is a very good drug," said Dr. Sidney Wolfe, executive director of Public Citizen's Health Watch group. But he added: "You could warn people better than what looks like the case right now, and allow the use to be safer."
A spokeswoman for Eli Lilly & Co., which makes Zyprexa, maintains the drug is safe and effective. "No one has yet proved any sort of causality," said Marni Lemons, the spokeswoman.
Zyprexa has been the Indianapolis-based drug maker's top-selling medication - surpassing even the popular antidepressant Prozac - since it went on the market in 1996. With more than 11 million people taking Zyprexa worldwide, global sales approached $4 billion last year, Lemons said.
Psychiatrists and other researchers agree that Zyprexa has helped in treating schizophrenia - a disease characterized by incoherent thinking, disordered memory and delusions - and in managing bipolar disorder, in which sufferers swing between moods of elation and depression.
It is part of a "second generation" of anti-psychotic drugs that have come on the market in the past decade or so, which treat mental illness without the jerky movements, facial disfiguration and other side effects of traditional anti-psychotic medications.
Yet there have been reports since the late 1990s noting that patients taking Zyprexa - as well as some of the other new anti-psychotics - seem prone to diabetes and related illnesses.
In July, researchers from Duke University and the FDA identified 289 reports of patients taking Zyprexa who had developed diabetes or hyperglycemia. They tallied 23 deaths from the mid-1990s through February of last year in the journal Pharmacotherapy.
Though the researchers concluded that the deaths and the drug were linked, Dr. Robert W. Baker, Lilly's senior clinical research physician, says the evidence is not persuasive. "It's especially hard to know what would have happened to those people on some other treatment or no treatment at all," he said.
Baker noted that Zyprexa's label does mention that both diabetes and hyperglycemia were reported during clinical trials of the drug. They are listed among dozens of "infrequent" adverse effects reported while using the medication.
FDA's Cruzan said the agency did not see any "affirmative evidence" that Zyprexa causes or worsens diabetes before approving the drug in the mid-1990s. "That is still the outstanding question," she added.
Complicating the issue is research showing that more schizophrenics are diabetic or prone to diabetes than the general population, even without taking anti-psychotic medications.
"There appears to be some kind of link, we don't really understand its nature," said Dr. Lisa Dixon, a psychiatrist at the University of Maryland medical school and with the Veterans Affairs Hospital.
But Dixon and Dr. William Carpenter, director of the Maryland Psychiatric Research Center at UM, said there are enough reports linking diabetes with anti-psychotic drugs - particularly Zyprexa and an older drug, Clozaril - to be careful about prescribing it for patients who are already overweight. One of Zyprexa's best-known side effects is weight gain, and obesity can lead to diabetes.
Many who have developed diabetes while taking Zyprexa, like Amanda Yates of Glen Burnie, had no history of it. The 27-year-old insurance adjuster made two trips to the emergency room for dangerously high blood-sugar levels and had to take daily injections of insulin for several months to get her condition under control. Once her doctor took her off Zyprexa, she recovered.
"I'm just very, very lucky," she said.
Japan's Health Ministry, concerned by reports of two deaths and seven comas, barred doctors last year from prescribing Zyprexa for any new patients with diabetes, and warned them to monitor closely those already on the drug by regularly measuring blood-sugar levels. British drug regulators issued a warning in April.
Lilly has been making efforts to alert physicians to diabetes risks in mentally ill patients through company-sponsored seminars, but the firm disagrees with Japan's action, Lemons said. Putting warnings on the drug's label "has the potential to misinform patients and their caregivers, causing them to cease taking the medication."
Rob Liversidge had conquered his mood swings and suicidal thoughts after two years of treatment with Zyprexa, his mother said. Of average weight before he started taking the pills, he gained up to 100 pounds on the drug. "He didn't feel he had that many choices. He had been on the old anti-psychotics, and he said they made him feel like a robot," his mother said.
No one had warned him, though, to have his blood-sugar level checked for signs of hyperglycemia, which ultimately killed him, she says.
Ellen Liversidge has hired a California law firm and is considering filing a lawsuit against Lilly. Yet she says her chief aim is to alert others to the potential hazards of the drug.
"I think it helped Rob," she says. "I'm not damning the drug. I'm damning the fact there was no warning on the label."