Widely prescribed anti- psychotic drugs, such as Eli Lilly's top-selling Zyprexa, do not help most Alzheimer's patients with delusions and aggression and are not worth the risk of sudden death and other side effects, the first major study on sufferers outside nursing homes concludes.
The finding could increase the burden on families struggling to care at home for relatives with the mind-robbing disease.
"These medications are not the answer," said Dr. Thomas Insel, director of the National Institute of Mental Health, which paid for the study. He said better medications are at least several years away.
Three-fourths of the 4.5 million Americans with Alzheimer's disease develop aggression, hallucinations or delusions, which can lead them to lash out at caregivers or harm themselves. This behavior is the most common reason families put people with Alzheimer's in nursing homes.
The study tested Zyprexa, Risperdal and Seroquel -- newer drugs developed for schizophrenia. Doctors are free to prescribe them for any use. However, the drugs carry a strong warning that they increase the risk of death for elderly people with dementia-related psychotic symptoms, mainly because of heart problems and pneumonia, and that they are not approved for such patients.
Zyprexa, made by the Indianapolis drug maker Eli Lilly and Co., is not marketed by Lilly to treat aggression or delusions in Alzheimer's patients. Sales of Zyprexa last year totaled $4.2 billion, making it Lilly's top drug.
"We are not approved to treat elderly patients with dementia. This is a very sensitive patient group," said Lilly spokeswoman Carole Puls on Wednesday.
Zyprexa is federally approved and marketed by Lilly for two conditions: schizophrenia and the manic phase of bipolar disorder. Lilly isn't allowed to promote Zyprexa for other uses, although doctors are free to prescribe the drug for any condition, including Alzheimer's.
Yet roughly one-quarter of nursing home patients are on these drugs, and at least that many patients at home have used them, mainly because there are no great alternatives and there was some evidence they might help a little, experts say.
The study tested the drugs on 421 patients at 42 medical centers who needed considerable care but were living in their own homes, a relative's home or assisted-living facilities. The findings were reported in today's New England Journal of Medicine.
Each patient got one of the drugs or a dummy pill, without knowing what they received. The doctor could raise the dose if needed. Patients were followed for nine months, longer than in most previous tests.
About four in five patients stopped taking the pills early -- on average, in five to eight weeks -- because the medications were ineffective or had side effects that included grogginess, worsening confusion, weight gain and Parkinson's-like symptoms such as rigidity and trouble walking.
Five deaths were reported among the patients on the medication, versus two in the placebo group. But researchers said the difference could be a matter of chance. The causes of death were not disclosed.
Symptoms did improve in about 30 percent of patients taking the drugs, as well as in 21 percent of those getting dummy pills, partly because symptoms can naturally wax and wane.
Some patients who stopped taking one pill were switched to another treatment for the study's second phase, results of which are to be reported next spring.
While the federal government paid for the study, the medications were supplied by the makers: AstraZeneca Pharmaceuticals, maker of Seroquel; Lilly, maker of Zyprexa; and Johnson & Johnson, maker of Risperdal. Most of the researchers have received industry grants or consulting or lecture fees.
Dr. Jason Karlawish of the University of Pennsylvania's Alzheimer's Disease Center wrote in an editorial that the drugs did help a small group of patients who had few or no side effects. He said Zyprexa and Risperdal both were better than Seroquel or the placebo in treating the behavioral problems.
Lead researcher Dr. Lon Schneider, director of the Alzheimer's Disease Center of California and a University of Southern California professor, said doctors should try the drugs if necessary, but watch patients closely and switch to something else after a few weeks if there is no improvement or side effects are too severe.
"Patients are put on these kinds of medications and not particularly monitored and treated for indefinite periods of time," Schneider said. "That just maximizes risk."
source: http://www.indystar.com/apps/pbcs.dll/article?AID=/20061012/BUSINESS/610120423/1003/BUSINESS 12oct2006
Antipsychotic drugs commonly prescribed for restive Alzheimer's patients rarely improve their condition, according to a new study that comes as a blow to what many hoped was a promising new treatment for the debilitating disease.
While relatively benign memory loss is one characteristic of Alzheimer's, more than half of the nation's 5.5 million patients also develop delusions, hallucinations and aggressiveness. Such symptoms increase with age, making care difficult. To deal with such problems, geriatric specialists have increasingly prescribed antipsychotic drugs that started being sold in the 1990s as a second generation of drug treatments for schizophrenia.
The study, published in this week's New England Journal of Medicine, compared the effects of three such antipsychotic drugs with that of a placebo. The drugs were Zyprexa made by Eli Lilly & Co., Risperdal made by Johnson & Johnson, and Seroquel made by AstraZeneca PLC.
The trial followed 421 patients at 45 sites and was conducted between 2001 and 2005. Patients were randomly assigned either a placebo or one of the drugs. The patients were treated in normal clinical fashion, with doctors starting with low dosages and then increasing them until the patient either responded positively or couldn't tolerate the treatment.
Clinicians discontinued use of the drugs for between 77% and 85% of the patients involved within nine months, either because the patient couldn't tolerate the drugs or wasn't getting any benefit.
The study found that 21% of the patients taking the placebo had at least minimal improvement after 12 weeks. The proportions of drug-taking patients who exhibited similar changes were 32% for Zyprexa, 29% for Risperdal and 26% for Seroquel.
The researchers said the difference between the placebo and the drugs wasn't statistically significant and was offset by the higher percentage of patients who had to discontinue the drugs because of side effects. The study concluded "there is no large clinical benefit of treatment" with the drugs "compared with placebo."
Lead author Dr. Lon S. Schneider of the University of Southern California Keck School of Medicine said in an interview that, despite the study's results, it is still worth trying such drugs because "they work in some cases and there aren't great alternatives." He said the researchers were also concerned their study might lead some insurers to balk at paying for the pricey drugs for Alzheimer's patients.
Dr. Bruce Kinon, a research psychiatrist at Eli Lilly, said the findings reflect "the difficulties in treating these patients" and show that Alzheimer's symptoms are different than those of schizophrenia or bipolar disorder, for which Zyprexa is approved.
A spokesman for AstraZeneca, which sold $2.8 billion of Seroquel last year, said it wouldn't comment since it isn't seeking to have the drug approved for Alzheimer's treatment. A spokesman for J&J said the study shows the need for further research and noted that no treatment for agitated Alzheimer's patients has been approved by the Food and Drug Administration.
The study may limit what had been considered a potentially big new market for the drugs, which already bring in billions of dollars in revenue for their makers. The size of the Alzheimer's market for such psychotropic drugs isn't clear, however, because the FDA doesn't approve them for treatment of dementia.
Doctors can still prescribe them for such use, but the FDA requires a so-called black-box warning indicating that they cause an increased risk of death and aren't approved for Alzheimer's patients. Dr. Schneider said that despite the warning, as many as half of all Alzheimer's patients in nursing homes get the drugs at some point.
Unlike most drug trials, which are funded by pharmaceutical makers, this study was paid for by the National Institute of Mental Health. Many of the authors have, however, received consulting fees and other funds from the psychotropic drugs' makers.
An accompanying editorial in the New England Journal, written by Dr. Jason Karlawish of the University of Pennsylvania, praised the study for taking into account patients who dropped out and said it better reflects how drugs are used in the real world.
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