Superiority of New Schizophrenia Drug Challenged

Study: Olanzapine good, but not much better than cheaper standby

TUESDAY, Nov. 25, 2003 (HealthDayNews) -- Bucking previous reports, new research suggests that a state-of-the-art drug to treat schizophrenia doesn't earn its significant premium when compared with an older and much cheaper medication.

Earlier research had found that the newer drug, olanzapine, was worth its almost $8 a day more per patient than the most frequently prescribed medication, haloperidol, because olanzapine reduces symptoms and prevents psychotic relapses better. And experts have argued that while olanzapine and its ilk cost more than older drugs, they save money over time by reducing hospitalizations and other health care expenses.

However, the latest study found each patient treated at Veterans Administration hospitals with olanzapine cost that system between $3,000 and $9,000 more each year, on average, than patients on haloperidol. But the researchers didn't see a significant improvement in symptoms or quality of life for the added expense.

So should doctors avoid the new and stick to the old? Perhaps not just yet.

"The reason I'm not prepared to come to that conclusion is that this is just one study," says Dr. Robert Rosenheck, the leader of the new research and the director of the VA's Northeast Program Evaluation Center in West Haven, Conn.

Olanzapine does appear to be less likely than haloperidol to cause serious motor symptoms, called tardive dyskinesia, which are linked to long-term use of antipsychotics. If that's the case, Rosenheck says, use of the more expensive drug might be justified. However, only longer studies will tease out that benefit.

Marni Lemon, a spokeswoman for Eli Lilly and Co., which sells the drug as Zyprexa, says the company is "supportive of this type of research." And while her company, in fact, funded the study, she adds, "It's important to note that it is only one study, with significant limitations."

The patients in the study were "very ill," Lemon says, noting they had the disease for an average of 22 years.

"These are people who have been sick for a long, long time, and are very difficult to treat," she says.

She also says that the cognitive improvement and reduced restlessness associated with the newer drug are important advantages.

Rosenheck, who is also a professor of psychiatry and public health at Yale University Medical School, says he was surprised by the results until he reviewed the medical literature. In one of his textbooks, he read that patients on the older antipsychotic drugs sometimes appear depressed or psychotic when, in fact, they have gait and motor problems that resemble Parkinson's disease -- problems that can be helped with additional medication.

The Food and Drug Administration raised that very issue in the mid-1990s when it was considering whether olanzapine was superior to haloperidol, says Rosenheck, who used a Freedom of Information Act petition to ferret out that information.

The FDA noted at the time that studies comparing olanzapine and haloperidol, or Haldol, might be overstating the benefits of the new drug by confusing the side effects of Haldol with failure, Rosenheck says.

A report on the latest findings appears in the Nov. 26 issue of the Journal of the American Medical Association.

Olanzapine belongs to a family of drugs called atypical antipsychotics. These medications, which also include Janssen's Risperdal, are considered "atypical" because, unlike older psychosis treatments, they don't cause muscle and nerve side effects like tremors and twitches.

But doctors frequently prescribe medications to suppress the shaking complications with the "typical" antipsychotics.

Recognizing this pattern, the latest study compared olanzapine and haloperidol in a "real world" setting by pairing haloperidol with benztropine, a drug also used to control muscle stiffness and tremors in people with Parkinson's disease.

The researchers followed 309 schizophrenic patients at 17 VA hospitals nationwide. Of those, 159 received olanzapine and 150 took haloperidol and a preventive dose of benztropine.

Many patients dropped out of the study before it ended, though the number who left was roughly the same in each group.

After a year, the researchers say, the two drugs seemed equally effective at preventing psychotic symptoms like hallucinations, delusions, and confusion. Patients in each group had similar quality of life on several measures, including their ability to maintain relationships, to function in the world, and their overall sense of well-being.

Patients taking olzanapine did have fewer muscle and movement side effects than those on haloperidol, as well as less restlessness and slightly better scores on memory tests.

Still, Rosenheck says, "the biggest thing you want to see is differential improvement in quality of life, and there was no significant difference" between the two drugs.

More than 80 percent of schizophrenics in the VA system now take atypical antipsychotics, with 38 percent on olanzapine. In fiscal year 2003, the VA spent $208.5 million on the mind drugs, including $106.6 million on olanzapine.

Dr. Robert Conley, a psychiatrist at the University of Maryland in Baltimore, says the study "is definitely going to have an effect on the field" of schizophrenia treatment. However, Conley says, the study is far from definitive. The vast majority of patients were men, and all were in the VA system. "It might not be generalizable outside the VA," he says.

In addition, the researchers studied only a small fraction of the nearly 4,400 schizophrenics they initially screened, meaning the group they looked at might not represent the larger pool. Finally, he adds, benztropine and related drugs can cause side effects, including cognitive problems, urinary trouble and severe constipation.

More information

For more on schizophrenia, try the National Alliance for the Mentally Ill or the National Institute of Mental Health.

SOURCES: Robert Rosenheck, M.D., director, Northeast Program Evaluation Center, Veterans Administration, West Haven, Conn., and professor of psychiatry and public health, Yale University Medical School, New Haven, Conn.; Robert Conley, M.D., professor of psychiatry and pharmacy science, University of Maryland, Baltimore; Marni Lemon, spokeswoman, Eli Lilly and Co., Indianapolis; Nov. 26, 2003, Journal of the American Medical Association
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