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Cost Benefits of New Schizophrenia Drugs Doubted
Older Medication, Considered Equally Effective, Can Be as Much as $600 a Month Cheaper, Study Finds

By Shankar Vedantam
Washington Post Staff Writer
Friday, December 1, 2006

Treating schizophrenia with an older, cheaper drug, rather than with heavily promoted newer medications, reduces the cost by as much as 30 percent with no apparent difference in safety and effectiveness, according to the first study to examine the economic implications of antipsychotic drug prescribing practices in the United States.

The newer drugs, such as Zyprexa, Seroquel and Risperdal, have cornered the lucrative U.S. market for antipsychotic drugs at a cost of $10 billion a year -- or around $100 for every family.

The findings have roiled the field of psychiatry in a fierce debate over the study's implications and have triggered concerns it could lead public and private insurers to limit drastically which drugs they will pay for.

Earlier research had shown that the older drug was as safe and effective as the newer medications. But experts cautioned against assuming that the cheaper drug would be as cost-effective once hospitalizations, side effects and quality-of-life issues were taken into account.

The new study, published today in the American Journal of Psychiatry, concluded that when those factors were included, monthly costs per patient were $300 to $600 lower with the drug perphenazine, which is no longer under patent. The finding is the latest result from the $42 million Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE), a federal study into the treatment of schizophrenia.

In an indication of the widespread unease in the psychiatric establishment over the results , one senior doctor who helped conduct the study but not the cost-effectiveness assessment said the new finding faced stiff headwinds before it was published, and was subjected to an extraordinary level of review.

"You are saying perphenazine is $500 cheaper," said the doctor, who spoke on condition of anonymity because of the sensitivity of the issue , to explain why many psychiatrists weighing the study seemed aghast. "Now the physicians feel defensive, because people will ask, 'Why are you charging the patient and insurance company $500 more when the drugs don't give you anything more?' "

This doctor, the study's authors and several leading psychiatric experts, including Thomas R. Insel, director of the National Institute of Mental Health, emphasized that the study does not mean that patients doing well on more expensive drugs should be switched to cheaper medication. Switching drugs involves potential problems, and patients doing well on a drug should be kept on it, they said .

But because many patients with schizophrenia need to change medications frequently -- an earlier part of the study found that three-quarters of patients discontinue whatever drug they are on within 18 months -- many could become candidates for treatment with the less expensive drug in a short period of time.

"If they are chronically ill and are not on medication or want to switch, it is certainly a rational choice and would save money, and for the most part we can't detect effectiveness differences," said Robert Freedman, editor in chief of the journal, who co-wrote an editorial accompanying the study.

Freedman and several experts said they were very worried, however, that the choice of medications would be taken from physicians and would be decreed by insurers. That would ignore the complexities of treating schizophrenia and the need for flexibility, the experts said.

Patients who have tried perphenazine unsuccessfully, for example, may not be good candidates to go back on it. The federal study looked only at people who had had schizophrenia for a long time, not newly diagnosed patients. And overall, the fact that patients are dissatisfied so often with medications, including perphenazine, means that flexibility remains key.

In statements, drugmakers AstraZeneca, which makes Seroquel, and Eli Lilly and Co., which makes Zyprexa, said patients benefit from having individualized treatment. The federal Centers for Medicare and Medicaid Services -- Medicaid picks up three-quarters of the $10 billion tab for antipsychotic drugs -- also believes that physician discretion is essential, a spokesman said.

Drug-industry critic Jerry Avorn, author of the book "Powerful Medicine: the Benefits, Risks, and Costs of Prescription Drugs" and a professor of medicine at Harvard Medical School, said this is not a case of difficult trade-offs between cost and quality.

"The cheapest drug produced an effect that was as good as the more expensive drugs," he said. "The resistance to this kind of finding comes from . . . the very legitimate worry that boneheaded cost containers will read this study and then try to get every schizophrenic on every other medication to be switched to the cheapest available product. I am a proponent of educating doctors first rather than tying our hands."

Both Insel and Robert Rosenheck, the Yale University psychiatrist who led the cost-effectiveness study, said the message was not that the half-dozen expensive new drugs should be replaced by perphenazine. Rather, they said, the message of the CATIE study is that once a range of side effects is taken into account, many older antipsychotic drugs may have risks and benefits that are similar to those of the newer drugs.

"It triples the size of the antipsychotic armamentarium available to psychiatrists," Rosenheck said. "Before CATIE, we had five to six drugs and we had tremendous pressure to not use the other 15. What CATIE has said is doctors should feel free to use whatever medicine is right for their patient, and there are 19 or 20 choices, not five or six."

Although both old and new classes of drugs have similar effectiveness in controlling symptoms such as delusions and hallucinations, the advent of the newer drugs was hailed because they seemed less likely to cause side effects involving involuntary muscle movements.

But evidence has gradually accumulated that the newer drugs do cause weight gain and serious metabolic problems. Essentially, the editorial noted, the new medications have resulted in a change in side effects, rather than eliminating them.

Rosenheck said the study means that patients paying for expensive new drugs out of pocket who wanted to switch could try perphenazine without the concern that they are getting inferior treatment. The magazine Consumer Reports recently listed perphenazine, which is sold as a generic drug, as a "best buy" among antipsychotics.

While Rosenheck and CATIE lead scientist Jeffrey Lieberman of Columbia University disagreed with the authors of the editorial on how to interpret several aspects of the study, everyone agreed that the trial provides the best window in the country to date on the treatment of schizophrenia. The editorial said the study highlighted the need for new and better treatments -- and perhaps a new and better mechanism of financial rewards to spur their development.

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