Study Shows Lilly's Zyprexa Works Only as Well as "Typical" Drug Costing Pennies per Dose

A study comparing a pennies-a-day schizophrenia drug with a far more expensive and widely prescribed Eli Lilly & Co. drug found no difference between the two in reducing schizophrenia symptoms and improving quality of life.

The results of the Lilly-sponsored study, published in this week's Journal of the American Medical Association, run counter to those of some earlier studies. In those earlier studies it was found that Lilly's Zyprexa -- the more expensive drug -- improved symptoms and quality of life and lowered health-care costs when compared with Haldol, largely by cutting down on hospitalization of schizophrenic patients.

Indeed, before they began enrolling patients, the authors of the JAMA study, a randomized trial that followed 309 military veterans for a year, believed the results would mirror the prior studies' findings and initially were surprised by their results. Upon further review, the principal author, Robert Rosenheck, said he found some problems in the design of some of the major prior studies.

"We need to rethink what we're getting for what we're paying," said Dr. Rosenheck, director of the U.S. Department of Veterans Affairs Northeast Program Evaluation Center in West Haven, Conn., and a professor of psychiatry and public health at Yale Medical School. "The profound issue in health care is do we pay anything -- regardless of the price -- for a statistically significant benefit?"

The participants in this study, which was conducted by doctors at 17 VA hospitals, don't mirror the general population: Nearly all were men -- with an average age of 46 -- who had been suffering from schizophrenia for about two decades. Still, in an era marked by sharply rising health-care costs, the study is likely to raise questions about what many doctors have seen as a costly but worthwhile first-line treatment for a debilitating disease. According to the study, about two million people in the U.S. suffer from schizophrenia, a psychotic disorder marked by delusions and hallucinations.

Zyprexa didn't reduce hospital stays, according to the study. Zyprexa was associated with substantially greater costs, ranging from $3,000 to $9,000 a patient annually. Zyprexa typically costs the Department of Veterans Affairs $8 a day per patient, while Haldol costs six cents a day, the agency said.

Alan Breier, Lilly's chief medical officer, said he didn't believe the study would prompt doctors to revert to prescribing Haldol or other older drugs before Zyprexa. Instead, he said, doctors need to look at the "totality of the literature" on Zyprexa. The drug had world-wide sales of $4.1 billion during the year ended Sept. 30 and makes up more than one-third of the Indianapolis drug maker's revenue. "I think it's important not to draw black-and-white conclusions from one study," Dr. Breier said.

Patients were randomly assigned to Zyprexa or Haldol and neither the doctor nor the patient knew which drug was being used. Patients taking Haldol also were given another drug to prevent tremors and other Parkinson's-like side effects of Haldol; that drug also costs pennies a day. (Zyprexa patients were given an inert companion pill to mimic the side-effect medication taken with Haldol.)

Patients taking Zyprexa were less likely to suffer from mild akathisia, a feeling of inner restless, and more likely to perform slightly better on tests that measure memory and fine movements. When adjustments were made to account for those who switched medications, the patients in the Zyprexa group also had fewer symptoms of tardive dyskinesia, a neurological problem that causes repetitive, involuntary movements, such as smacking lips, grimacing and rapidly moving arms and legs. But none of those benefits, when assessed by patients and trained raters, led to a greater quality of life for patients using widely accepted measures, the researchers concluded.

Still for some doctors, those benefits are enough to merit prescribing Zyprexa as a first-line treatment. "Even mild akathisia can be tormenting," said Stephen R. Marder, a professor at UCLA Neuropsychiatric Institute.

Zyprexa patients in the study also were more likely to report substantial weight gain than those on Haldol and the side-effect drug. That is a concern because the Food and Drug Administration recently required Lilly and other makers of drugs in that class to carry warning labels on the drugs about a possible risk of diabetes.

In the study, patients unhappy with their treatment could switch to another medication. The data were analyzed to make sure that medication switches didn't bias the results.

The study set out to recruit about 600 participants and ended up with about half that, although it had enough patients to draw statistically valid conclusions. Nonetheless, Dr. Breier, of Lilly, said the results could have been skewed by 28 patients for whom treatment costs exceeded $50,000. Of those "outliers," 17 were in the Zyprexa group, a Lilly spokeswoman said.

Dr. Rosenheck says Lilly suggested excluding those higher-cost patients from the analysis, which he refused to do. He crunched the data using four different methods to address the skewed distribution, each time coming up with the same results. "They began to suggest things that I did not feel comfortable publishing under my name," he said. "When we do research, we generally don't throw out data." A Lilly spokeswoman declined to comment.

Dr. Rosenheck knows of no prior studies comparing Zyprexa and Haldol that used a companion drug to prevent Haldol's side effects. Instead, he found some studies used a companion drug once the symptoms emerged. That is a problem, he said, because telltale symptoms let patients and doctors know that Haldol was used, prompting some patients to drop out. In addition, he said, some side effects may be mistaken for symptoms of schizophrenia. All of those factors could bias the results, he said.

In the yearlong study, Rosenheck and his coauthors enlisted 309 patients with schizophrenia at 17 Veterans Affairs medical centers. Half were given olanzapine and the other half were given haloperidol and a drug called benztropine to control side effects. Neither doctors nor patients knew which drugs were administered.

The scientists found that haloperidol patients had mildly diminished scores on cognitive tasks and a slightly increased rate of tardive dyskinesia, along with the slightly increased rates of akathisia. Patients on olanzapine experienced more weight gain.

The scientists detected no statistically significant difference between the two groups in overall quality of life or symptoms of schizophrenia.

Dr. John M. Kane, executive director of the Zucker Hillside Hospital in New York City, cautioned that the population of patients in the study was not completely representative: They were older and had been ill for about 20 years.

A longer, National Institutes of Health-funded study comparing an older, haloperidol-like drug to four of the newer medications in 1,500 people is currently underway.

 

Sources: Information compiled from the following news sources, and related stories:
Older, cheaper schizophrenia drug as effective as newer one: ...
Canada.com, Canada - Nov 26, 2003

Study Questions New Schizophrenia Drug
Newsday - Nov 25, 2003

Benefits of Newer Schizophrenia Drug in Doubt
MSNBC - Nov 25, 2003
 

Weighing the Costs of Schizophrenia Drugs - HealthCentral

 

Wall Street Journal

Smell test 'spots schizophrenia'
Source: BBC News

Simple smell tests could help doctors identify people at risk of developing schizophrenia, a study suggests.
 

It has long been known that people with schizophrenia or psychosis are unable to correctly identify smells.

But until now scientists were unsure whether this occurred before or after symptoms developed.

This latest study, published in the American Journal of Psychiatry, suggests it happens before the first symptoms appear.

High risk patients

Dr Warrick Brewer and colleagues at the University of Melbourne examined a group of people, all of whom were deemed to have a very high risk of developing psychosis.

They found those who went on to develop schizophrenia, rather than other forms of psychosis, were all unable to identify smells properly.

For instance, they thought the smell from a pizza actually came from an orange or the smell of bubblegum was actually smoke.

This problem was present before the onset of any significant clinical symptoms of psychosis.

The researchers believe their findings could lead to a new test for schizophrenia, which could in turn transform the way people with the condition are treated.

"An accurate and reliable diagnostic tool for schizophrenia could allow for early treatment or prevention and minimise the extensive and significant distress to those in the community directly and indirectly affected," said Dr Brewer.

The researchers believe that changes in the brain in the very early stages of schizophrenia may prevent people from identifying smells properly.

"It is the only sense that passes straight to this area of the brain," said Dr Brewer.

"Any vulnerability involving these neural circuits can affect our labelling of smell."

'Quite useful'

Professor Philip McGuire of the Institute of Psychiatry in London said the findings were promising.

"It sounds like a strange idea but it makes sense," he told BBC News Online.

"The part of the brain that perceives smells connects parts of the brain implicated in schizophrenia.

"If we were able to use a simple test of how we smell things to identify those at super risk of developing schizophrenia, that would be quite useful.

"Other people are trying to identify other biomarkers with brain scans, for instance. But these are quite expensive.

"Being able to do it in just a few minutes with a simple test is potentially very useful."

He said further studies are needed before doctors could adopt the technique.

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/3224437.stm

For more information see:

Could You Suffer From Psychosis? The Nose Knows (Science Daily)

http://www.sciencedaily.com/releases/2003/10/031029064717.htm
 

Schizophrenia: early detection study

http://www.abc.net.au/worldtoday/content/2003/s991964.htm

Study: Schizophrenia Risk of Children, Increases with Father's Age
Thu October 30, 2003 07:14 PM ET

Children fathered by older men have an increased risk of schizophrenia in later life, possibly because of mutations in their father's DNA, according to a new study from Sweden published Friday.
 

A link between paternal age and schizophrenia has been reported before but scientists were not sure whether this was due to increasing mutations with advancing age or the result of inherited personality traits.

To find out, researchers at the University of Wales College of Medicine in Cardiff and Gothenburg University in Sweden examined the medical records of 50,087 Swedish army conscripts recruited between 1969 and 1970.

The study found that the odds of developing schizophrenia increased by 30 percent for each 10-year increase in paternal age.

"This supports the hypothesis that accumulating germ cell mutations may lead to an increase in genetic liability to schizophrenia in the offspring," Dr Stanley Zammit, from the University of Wales, said.

Source: British Journal of Psychiatry

Scientists identify more genes linked to schizophrenia

Scientists have identified three genes that could play a role in causing schizophrenia, a German researcher said.

"After 10 years without any real success, we have now determined three candidate genes," Germany's Saarland University Professor Peter Falkai said.

Professor Falkai said the genes Dysbindin, Neuregulin and G72 had been identified but that anywhere from 50 to 100 genes could be involved in causing schizophrenia.

Speaking at a conference of the German Research Network on Schizophrenia, a government healthcare research program, Professor Falkai said the findings were made by several working groups, with German scientists playing a significant role.

He said about half the cases of schizophrenia, which usually manifests itself during late adolescence or early adulthood, were probably caused by the genes with the other half due to environmental triggers.

Those could include complications at birth or during pregnancy, viral illnesses, hashish consumption and high stress levels in cities.

University of Bonn professor Wolfgang Maier described the progress made on the disease, which hits about one in 50 people, as a "crucial breakthrough".

While findings suggested that medicine currently used to treat schizophrenia was relatively effective, the gene findings could lead to new treatments.

"Instead of symptomatic therapy, we now have the chance to develop a selective causal therapy," Professor Falkai said.

http://www.abc.net.au/news/newsitems/s973351.htm