Study Shows Lilly's Zyprexa
Works Only as Well as "Typical" Drug Costing Pennies
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
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
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
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
Story from BBC NEWS:
For more information see:
Could You Suffer From Psychosis? The Nose Knows
Schizophrenia: early detection study
Study: Schizophrenia Risk
of Children, Increases with Father's Age
October 30, 2003
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
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
"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
of Excerpt: http://www.abc.net.au/news/newsitems/s973351.htm