September 19, 2005
A landmark study led by University of North Carolina at Chapel Hill School of Medicine researchers has found that a drug used since the 1950s to treat people with schizophrenia works about as well as four newer, more expensive drugs introduced in the 1990s.The study also found that one of the newer drugs, olanzapine (brand name: Zyprexa), was slightly better than the other drugs but was associated with significant weight gain as a side effect.

“The good news is that we have more medications that are useful than we thought, and we have high-quality information that will help in making choices,” said UNC’s Dr. Scott Stroup, a co-principal investigator in the Clinical Antipsychotic Trials of Intervention Effectiveness, which is also known by the acronym CATIE. The other co-principal investigator is Dr. Joseph McEvoy, associate professor of biological psychiatry at Duke University Medical Center.

Stroup is an associate professor in the department of psychiatry. UNC’s Dr. Diana Perkins, a professor in the department of psychiatry; and Dr. Ed Davis, professor and chairman of the department of biostatistics in UNC’s School of Public Health, also are key investigators in the study.

The first results to be reported from the CATIE trial, which began in 1999 and is run from UNC, are being published this week in the Sept. 22 issue of the New England Journal of Medicine. The National Institute of Mental Health (NIMH) funded the $60 million trial.

“The study has vital public health implications because it provides doctors and patients with much-needed information comparing medication treatment options,” said Dr. Thomas Insel, NIMH director. “It is the largest, longest and most comprehensive independent trial ever done to examine existing therapies for this disease.”

Schizophrenia, which affects 3.2 million Americans, is a chronic, recurrent mental illness, characterized by hallucinations, delusions and disordered thinking. The medications used to treat the disorder are called antipsychotics. Previous studies have demonstrated that taking antipsychotic medication is far more effective than taking no medicine, and that taking it consistently is essential to the long-term treatment of this disorder. The medications alone are not sufficient to cure the disease, but they are necessary to manage it.

In the CATIE trial, researchers directly compared the older drug perphenazine (which is now sold only as a generic medication) to four newer drugs: olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal) and ziprasidone (Geodon). The purpose of the study was to learn whether or not differences exist among the newer drugs and whether or not the newer drugs have any significant advantages over the older drug.

The newer drugs, which are called atypical antipsychotics, cost about 10 times as much as the older drug.

More than 1,400 patients took part in the trial at 57 sites nationwide. CATIE sites in North Carolina included UNC, Duke University Medical Center, John Umstead Hospital in Butner, Dorothea Dix Hospital in Raleigh and the Behaviorial Health Center in Charlotte. Quintiles Transnational, based in Research Triangle Park, provided extensive logistical support for the nationwide study.

Patients were randomly assigned to receive one of the five drugs. Almost three-quarters of patients switched from their first drug to a different drug during the study. The patients who started on olanzapine were less likely to be hospitalized for a psychotic relapse and tended to stay on the drug longer than patients taking other drugs. However, patients on olanzapine also experienced substantially more weight gain and metabolic changes associated with an increased risk of diabetes than patients taking the other drugs.

Contrary to the researchers’ expectations, movement disorder side effects such as rigidity, stiff movements and muscle restlessness were not seen more frequently with the older drug than with the newer drugs. The older medication was as well tolerated as the newer drugs and was equally effective as three of the newer drugs. The advantages of olanzapine – in symptom reduction and duration of treatment – over the older medication were modest and must be weighed against the increased side effects of olanzapine, the researchers said.

Thus, taken as a whole, the newer medications have no substantial advantage over the older medication used in this study. An important issue still to be considered is individual differences in patient response to these drugs, the researchers added.

Several factors, such as adequacy of symptom relief, tolerability of side effects and treatment cost, influence an individual’s willingness and ability to stay on medication.

“There is considerable variation in the therapeutic and side effects of antipsychotic medications,” said Dr. Jeffrey Lieberman, CATIE’s principal investigator. “Doctors and patients must carefully evaluate the tradeoffs between efficacy and side effects in choosing an appropriate medication. What works for one person may not work for another.”

Lieberman was a member of the UNC psychiatry faculty when CATIE began. Now he is chairman of Columbia University’s department of psychiatry and director of the New York State Psychiatric Institute.

The New England Journal of Medicine article addresses many of the primary questions from the study. Future reports stemming from CATIE will discuss additional topics (such as cost-effectiveness of the drugs, quality of life and predictors of response) and will provide a more detailed picture of the interaction between patient characteristics, medication and outcomes.

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UNC School of Medicine contact: Stephanie Crayton, (919) 966-2860 or scrayton@unch.unc.edu.

For further information please contact Ramona DuBose, director of communications for the UNC School of Public Health, by telephone at 919-966-7467 or by e-mail at ramona_dubose@unc.edu.

 

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