Schizophrenia Drug Face-Off: No Clear Winner

Surprise Finding: Older Antipsychotics Can Be as Good as New Ones

From the WebMD Archives

Sept. 19, 2005 -- Mental health experts say it wasn't a horse race. That explains why there's no clear winner from a major government study pitting a new generation of schizophrenia drugs against one another.

Zyprexa was the most effective of the drugs. But its greater number of side effects dims its first-place finish.

Meanwhile, a come-from-behind, second-place finish by Trilafon -- a little-known old horse that nobody thought had a chance -- may rescue the older generation of schizophrenia drugs from being put out to pasture.

Funded by the National Institute of Mental Health (NIMH), the five-year study enrolled 1,500 schizophrenic patients at 27 U.S. medical centers. Neither patients nor their doctors knew whether they were getting Zyprexa, Seroquel, Risperdal, Geodon, or the older Trilafon. Jeffrey A. Lieberman, MD, now director of the New York Psychiatric Institute, led the study while at the University of North Carolina in Chapel Hill.

"These drugs work, but have limitations: 74% of patients in the study elected to seek something better rather than stay on their assigned medication," Lieberman said today at an NIMH news conference. "When it comes to treatment, the glass is only half full. ... We all want more efficacy and fewer side effects. But make no mistake: These drugs do work."

The study findings appear in the Sept. 22 issue of The New England Journal of Medicine.

'Traditional' Drug vs. Newer 'Atypical' Drugs

Schizophrenia is a frightening mental illness afflicting 3.2 million Americans. Usually beginning at age 18 to 24, patients suffer hallucinations, delusions, and disordered thinking. There is no cure. But treatments can greatly reduce the intensity of symptoms.

"Fifty years ago we would have been talking about people institutionalized in state hospitals," NIMH director Thomas R. Insel, MD, said at the news conference. "Then there came drugs, such as Thorazine and Haldol, which proved quite effective in reducing symptoms and the need for hospitalization."

These traditional antipsychotic drugs can have devastating side effects resembling Parkinson's disease: tremor, rigid muscles, and abnormal or restless movements.

About 12 years ago, the new generation of "atypical" antipsychotic drugs came along. These drugs were much less likely to cause Parkinson's-like side effects. But they came with side effects of their own -- extreme weight gain and an increased risk of type 2 diabetes Even so, 90% of schizophrenia prescriptions are for one of these six drugs.

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Clinical trials show that the drugs work better than no drugs at all. But the trials never told doctors how the drugs would work relative to one another. That's why the NIMH sponsored the trial, known as the Clinical Antipsychotic Trials of Intervention Effectiveness or CATIE.

The trial included Trilafon to represent the traditional antipsychotic drugs. It also included four other atypical antipsychotics. Clozaril was not included in the first phase of the trial because it will be tested as a second-line treatment for patients who switch from one of the original drugs in the trial. Those results will be reported later.

A sixth atypical antipsychotic drug, Abilify, wasn't included because the FDA had not approved it by the time of the trial.

What happened in phase 1 of the CATIE trial?

"Zyprexa was somewhat better in efficacy but had the most side effects," Lieberman said. "The biggest surprise was that the oldest medication [Trilafon] was comparable to at least three of the new medications and not much worse than Zyprexa. Contrary to expectations, the old drug did not cause more Parkinson's symptoms than the new drugs."

Some scientists involved in designing the study hadn't even thought the old drugs were worth including in the trial, says study investigator Robert Rosenheck, MD, of Yale University.

"Many of us thought the question was decided and the old drugs were of no value," Rosenheck said at the news conference. "Because we were willing to ask a question that most people thought they knew the answer to, we were able to get a surprising answer."

Doctors Get New Insight

The study findings aren't what everyone hoped for, notes University of Colorado researcher Robert Freedman, MD, in an editorial accompanying the CATIE report.

"The results could be viewed as discouraging," Freedman writes. "No drug provided the majority of patients a treatment that lasted the full 18 months of the study. ... Only 36% of the patients receiving the most effective drug, [Zyprexa], completed the trial."

But Rosenheck tells WebMD that patients who are happy with their schizophrenia medication don't enter clinical trials.

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"We psychiatrists all know patients who have been on the same treatment for many years, even for decades," he says. "Those entering a trial are interested in switching. This is not representative of all patients, many of whom are quite stable -- just those interested in trying something new."

And many patients are hoping for something new.

"Only the minority of patients are unresponsive and cannot benefit from antipsychotic medications," Lieberman tells WebMD. "The switching you see is because the level of response they get from a medication is, for many people, less than what they, their doctors, their families, and their significant others would like to see."

Study investigator T. Scott Stroup, MD, MPH, of the University of North Carolina at Chapel Hill, tells WebMD that when treatment is carefully matched to an individual patient's needs, most patients find something that works.

Lieberman says that's the lasting value of the CATIE study. It gives doctors information -- a lot more information than was ever before available -- on how to match treatment effects and side effects to the needs of an individual suffering from schizophrenia.

Stay tuned. The coming months and years will see more reports as researchers analyze data from the various phases of the CATIE trial.

WebMD Health News

Sources

SOURCES: Lieberman, J.A. The New England Journal of Medicine, Sept. 22, 2005; vol 353: pp 1209-1223. Freedman, R. The New England Journal of Medicine, Sept. 22, 2005; vol 353: pp 1286-1288. News conference, National Institute of Mental Health, with Thomas R. Insel, MD, director, NIMH, Bethesda, Md. Jeffrey Lieberman, MD, chairman, psychiatry, Columbia University Medical Center; director, New York Psychiatric Institute. Scott Stroup, MD, MPH, University of North Carolina, Chapel Hill. Robert Rosenheck, MD, Yale University Medical School; Department of Veterans Affairs.
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