Healthy Skepticism Library item: 7028

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Publication type: news

Waters R.
New Schizophrenia Drugs No Better Than Older, Cheaper Generics
BLOOMBERG NEWS 2006 Dec 1
http://www.bloomberg.com/apps/news?pid=newsarchive&sid=aJ2HAZHLooSo

Abstract:

Newer antipsychotic medications used to treat schizophrenia are no more effective than the older drugs they have largely replaced though they cost 10 to 20 times more, according to a large new U.S.
government-funded study.

Newer drugs, such as Johnson & Johnson’s Risperdal, Eli Lilly & Co.‘s Zyprexa and AstraZeneca Plc’s Seroquel, account for more than 90 percent of the $10.5 billion-a-year U.S. antipsychotic drug market, largely paid for by federal and state governments.

The drugs were billed in the mid-1990s as causing fewer of the side effects known as tardive dyskinesia that made users of earlier medications like Haldol and Thorazine tremble, doze off and jerk involuntarily. Today’s study backed up earlier research suggesting the much-costlier new drugs are neither safer nor more effective than the older medications.

``The assumption was these medications would have superior efficacy, greater safety and ultimately result in better long- term outcomes,’‘ said study co-author Jeffrey Lieberman, chairman of Columbia University’s psychiatry department. ``The presumption when the public is paying $10 billion a year is that it is worth it.’‘

The 10-year history of the newer antipsychotics and the results of the current study throw those assumptions into question, Lieberman said in a phone interview yesterday. The new research was published in the American Journal of Psychiatry.

``The original understandings and expectations have not been met,’‘
Lieberman said. ``We’re paying more than the incremental value justifies and could probably use older medications that are less expensive.’‘

Cost-Effectiveness

Thomas Insel, director of the National Institute of Mental Health, which funded the $42.6 million research, said the study helped answer a key
question: Is it cost-effective to use these second-generation drugs instead of the less-expensive older ones?
``The answer from this paper is that the older drugs may be a better buy,’‘
Insel said.

In an earlier analysis from the same clinical trial, known by the acronym CATIE, Lieberman and his colleagues reported last year that among four of the newer schizophrenia drugs, only Zyprexa was slightly more effective than a 40-year-old medicine, perphenazine. Today’s report compared the cost effectiveness of the same antipsychotics.

In the trial, almost 1,500 schizophrenia patients were randomly assigned to take perphenazine or one of four newer drugs: Seroquel, Zyprexa, Risperdal and Pfizer Inc.‘s Geodon. The researchers evaluated the patients’ progress in various ways throughout the 18-month study and calculated the total costs.

More Costly

The researchers concluded that caring for patients taking the newer antipsychotics cost $300 to $600 more each month than for those on perphenazine, depending on which of the new drugs they took. The analysis included the cost of the drugs as well as medical care, hospitalization, social services and other treatment related to the patients’ mental illness.

The cost difference was almost entirely attributable to the higher prices of the new drugs. The average cost to treat a patient on perphenazine was $960 a month — just $50 of that for the drug. Treating a patient with Zyprexa, the most expensive of the newer antipsychotics, cost $1,404 a month, and more than a third of that, $545, was for the drug.

The second-generation drugs that compete with Zyprexa cost less per pill, but the patients taking them incurred higher costs for care. Seroquel, which last year overtook Zyprexa as the top- selling antipsychotic, with $2.6 million in sales, costs $412 a month, while the total cost of care for patients taking it in the study was $1,478.

``When you look at total health-care costs, Zyprexa was the most cost-effective among the atypicals,’‘ said Carole Puls, a spokeswoman for Lilly, in a phone interview yesterday. The chief reason was the patients avoided hospitalization, she said.

Side Effects Less Likely

The advantage of Seroquel is that patients taking it are less likely to experience the neurological side effects that used to plague users of the older drugs, according to Arthur Lazarus, senior director of clinical research for AstraZeneca.

``Seroqeul has the best side-effect profile of all,’‘ Lazarus said in a phone interview yesterday. ``As a practicing psychiatrist, I would never subject a patient to the risks of tardive dyskinesia.’‘

The newer drugs were marketed in the mid-1990s almost as ``miracle drugs,’‘
said Joseph Glenmullen, a clinical instructor of psychiatry at Harvard Medical School and a critic of the overuse of psychiatric medications.

``The companies exaggerated their safety and promoted these drugs as not causing tardive dyskinesia,’‘ he said. ``It’s not true.’‘

New Side Effects

There is mounting evidence that the newer drugs can also cause tardive dyskinesia, though the relative rates are not yet clear. What is clear is that the newer drugs also cause another set of troubling side effects:
weight gain and metabolic changes that can lead to diabetes. Patients taking Zyprexa gained an average of 2 pounds a month, the study found.

With pharmaceutical companies funding so many drug studies, the National Institute of Mental Health should stop devoting most of its resources to funding them as well, said Vera Sharav, a critic of psychiatric medications and president of the Alliance of Human Research Protection, an advocacy group.

``NIMH has abandoned its mission by only funding drug studies,’‘ she said in a phone interview yesterday. ``There’s been no funding for alternative modalities of treatment.’‘

Not so, says NIMH director Insel.

``We spend a lot on psychosocial treatments,’‘ he said. ``No one would argue that medication should be the sum total. The worst thing that could happen is if we got into an either-or mindset.’‘

To contact the reporter on this story: Rob Waters in San Francisco at rwaters5@bloomberg.net .

Last Updated: December 1, 2006 00:16 EST ~~~~~~~~~~~~~~~~~~~

http://www.washingtonpost.com/wp-dyn/content/article/2006/11/30/AR2006113001
532_2.html
The Washington Post 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 Friday, December 1, 2006; Page A09

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.