Schizophrenia Daily News Blog

CATIE News & Commentary

The results from the CATIE study that were made public the other day (see CATIE STUDY RESULTS) are provoking a great deal of discussion and analysis in the world of people impacted by schizophrenia - as it well should. The sad, but simple fact is that despite all the money and research a lot less has been accomplished during the past 20 years than we thought, in terms of developing new and better therapies for people with schizophrenia. We can and must do better. We hope this will provide an incentive for biotech and pharma companies to increase their investment in new, innovative and clearly better new therapies for schizophrenia - and for the NIMH and FDA to do some deep thinking about how to improve the process. Over three million people's lives are at stake. I can't help but agree with NAMI's medical director that ""It underscores the need for greater investment in scientific research -- particularly in moving toward more effective, third-generation medications and ultimately a cure for schizophrenia."

Some short excerpts on the CATIE commentary that we've seen on the Internet:

New York Times editorial:

Comparing Schizophrenia Drugs

Published: September 21, 2005

A government-financed study has provided the strongest evidence yet that the system for approving and promoting drugs is badly out of whack. The study compared five drugs used to treat schizophrenia and found that most of the newest, most heavily prescribed drugs were no better than an older drug that is far cheaper. The nation is wasting billions of dollars on heavily marketed drugs that have never proved themselves in head-to-head competition against cheaper competitors.

The whole class of antipsychotic drugs has had undeniable value in blunting the symptoms of schizophrenia, enabling many patients to leave mental hospitals and move into the community. But the first generation of these drugs fell into disfavor because they often caused neurological side effects, like tremors and other involuntary movements.

That spurred the development of a new generation of drugs known as atypical antipsychotics, which now dominate the market and rake in some $10 billion in annual sales. The trouble is that these new drugs were approved largely on the basis of short-term clinical trials that compared them primarily with placebos, so there was little if any evidence that they were any better than many of the older drugs.

That gap has been filled by an 18-month clinical trial involving more than 1,400 adults around the nation. The study, sponsored by the National Institute of Mental Health, measured how long patients were able to keep taking their assigned drugs before deciding to change, usually because a drug wasn't working or had intolerable side effects. Three-fourths of the patients, a shocking number, stopped taking the drug they had been given, suggesting that there is a clear need for better treatments.

The study found that the oldest drug, perphenazine, was as effective and caused no worse side effects than three of the newer drugs. Zyprexa, a new drug made by Eli Lilly, helped patients control symptoms slightly better than the others, but at the cost of serious side effects.

Doctors should find a trove of useful data in the study to help them decide which drug might be best for a particular patient. But Congress and the Bush administration ought to pay attention as well. Surely it would make sense to force manufacturers to test their drugs not just against placebos, but against existing drugs that they are seeking to displace. And surely it would be cost-effective for the government to sponsor large studies comparing a slew of expensive drugs with their cheaper alternatives.

Little Difference Found in Schizophrenia Drugs (New York Times Reporting By BENEDICT CAREY)

..."The study, released yesterday and to be published Thursday in The New England Journal of Medicine, was widely anticipated because it is by far the largest, most rigorous head-to-head trial of the newer antipsychotics conducted without significant drug industry financing. The new drugs account for $10 billion in annual sales and 90 percent of the national market for antipsychotics.

The findings may not significantly alter the prescribing patterns of doctors in private practice, who often do not have to worry about cost, psychiatrists said. But they are likely to have an enormous effect on state Medicaid programs, many short on funds in part because of the high cost of schizophrenia drugs."

...

Several states, including Kentucky, West Virginia and Maine, have limited access to newer drugs, which cost 3 times to 10 times more than the older drugs. "The new study presents an opportunity but also a risk," said John Goodman, president of the National Center for Policy Analysis, a policy research group based in Dallas, which estimates that Medicaid programs spend at least $3 billion a year on antipsychotics, more than for any other drug class.

"The opportunity is to lower the cost of these drugs," Dr. Goodman said. "The risk is that state Medicaid programs use this excuse to entirely deny some patients access to more effective and more expensive drugs which work for those patients."

...

In the doses used in the study, a month's supply of perphenazine costs about $60, compared with $520 for Zyprexa, $450 for Seroquel, $250 for Risperdal and $290 for Geodon, according to Drugstore.com.

"Probably the biggest surprise of all was that the older medication produced about as good an effect as the newer medications, three of them anyway, and did not produce neurological side effects at greater rates than any of the other drugs," said Dr. Lieberman in an interview.

...

One thing that all agreed on was that the current state of schizophrenia treatment leaves a lot to be desired, and that the field longs for new and different drugs.

"The message is the glass is half full," Dr. Lieberman said. "The drugs work but they are not satisfactory to many patients, and three-quarters of the people in our study voted with their feet and discontinued the drugs."

Meanwhile, the American Psychiatric Association published this release on the CATIE trial:

"The American Psychiatric Association was an early supporter of CATIE and we continue to advocate for head-to-head comparisons of medications," said Darrel A. Regier, M.D., M.P.H., director of the APA's Division of Research. "CATIE shows that there's no one-size-fits-all treatment. None of these medications is without side effects and none is without substantial benefit. It is vital that we preserve access to a full range of medications and respect physicians' clinical judgments about which medication to use and when to change."

CATIE found that only 18 to 26 percent of patients remained on the initial medication for 18 months in all treatment groups except olanzepine (36 percent), validating clinicians' belief that, in order to offer the greatest benefit and the least adverse side effects for the individual patient, it is often necessary to try two or more medications.

In February 2004 the APA published the second edition of its guideline for treating patients with schizophrenia.

"This study contributes to our body of knowledge," said Anthony F. Lehman, M.D., M.S.P.H., who chaired the APA's work group on schizophrenia treatments. "From a public policy perspective, it would be a mistake to conclude that restricting access to any of the currently available antipsychotic medications is in the interest of patient care. Since all medications have potentially serious side effects, individual patient risk factors need to be considered in choosing a medication. The more choices, the better. This is consistent with the APA's Guideline on Treatment of Schizophrenia."

In his NEJM editorial accompanying the study, Robert Freedman, M.D., observed that the introduction of antipsychotic medications has had a profound social impact: today the vast majority of patients with schizophrenia are able to live in their communities as opposed to institutional settings. Treatment of schizophrenia has come a long way, but schizophrenia remains a mental illness that often requires long-term management.

"We commend NIMH for undertaking this large-scale clinical trial and we await more information from future reports from CATIE," said Dr. Regier, noting that the Thursday edition of the NEJM carries only the first round of findings from CATIE. "Schizophrenia is a severe medical condition that requires medical training and the patient's involvement to consider the metabolic and neurological side effects as well as the substantial benefits these medications can bring."

The National Alliance for the Mentall Ill (NAMI) had this to say in a press release:

The "Clinical Antipsychotic Trials of Intervention Effectiveness" (CATIE) are the largest comparative study of old generation and newer "atypical" medications ever conducted. Findings from the study, published in the New England Journal of Medicine, have implications for both the role of medication in treating schizophrenia and continued access to a range of options.

"The CATIE study is an important first step in giving physicians and
consumers basic information to make informed choices in selecting medications to treat schizophrenia," said NAMI medical director Ken Duckworth.

"It underscores the need for greater investment in scientific research -- particularly in moving toward more effective, third-generation medications and ultimately a cure for schizophrenia."

The study found that old and new medications are comparably effective, but both are also associated with a high rate (74%) of discontinuation by consumers due to side effects or incomplete control of symptoms.

Although older medications performed as well as newer medications, the study noted that based on previous research, newer agents "appear more efficacious than conventional drugs in reducing negative symptoms (e.g., lack of emotion, interest and expression)."

"For many Americans living with schizophrenia, newer generation
medications have made the difference in level of recovery," Duckworth said.

"For each person, the choice of medication must be made carefully. Different medications have different side-effects. They are not interchangeable."

Clinical factors affecting the choice of medication, include family
history, height, weight, ethnicity, and co-occurring conditions.

Future installments of the CATIE study also will address predictors of
response, cost-effectiveness, outcomes and quality of life.

"Discontinuation in taking medication is only one measurement of
effectiveness," Duckworth said.

NAMI noted that the study especially suggests the need for greater
research on non-adherence in taking medication, including:

*Those factors that influenced 26% of consumers to continue taking
medication in contrast to the large majority that discontinued treatment.

*The degree to which anosognosia (lack of insight) -- in which as many as 60% of persons with schizophrenia sometimes believe they are not sick -- may have contributed to the high rate of discontinuation.

*Other factors, such as improvements in symptoms, or ones unrelated to
the effects of medication.

"More research is needed, but clearly over time, CATIE's findings will
have a significant impact on decisions being made by states and other mental healthcare payers," said NAMI executive director Michael. J. Fitzpatrick.

"Treating individuals requires a range of individualized medication options,
but the bottom-line is that they must be evidence-based."