Differences seen in anti-psychotic drugs

WEST PALM BEACH, Fla., Sep 19, 2005 (United Press International via COMTEX) -- U.S. researchers said Monday they have found significant differences in the efficacy of five drugs used to combat the baffling disorder known as schizophrenia, as well as significant problems keeping patients on their medication regimens.

The anti-psychotic drug olanzapine -- Zyprexa, marketed by Eli Lilly -- topped the four other anti-psychotics, but only 36 percent of patients were able to remain on Zyprexa for the entire 18-month course of treatment, the researchers said.

In addition, the Clinical Antipsychotic Trials of Interventions Effectiveness, or CATIE, confirmed that patients treated with olanzapine also tended to gain weight and had adversely affected glucose and lipid metabolism, increasing their risk of developing obesity, diabetes and heart disease.

The other medications studied were:

-- clozapine, marketed as Clozaril by Novartis;

-- quetiapine, marketed as Seroquel by AstraZeneca;

-- risperidone, marketed as Risperdal by Janssen Pharmaceutica Products, and

-- ziprasidone, marketed as Giodon by Pfizer.

"Patients with chronic schizophrenia in this study discontinued their anti-psychotic study medications at a high rate, indicating substantial limitations in the effectiveness of these drugs," said Dr. Jeffrey Lieberman, chairman of the department of psychiatry at Columbia University in New York City, the lead author of the study, which is scheduled to be published Thursday in the New England Journal of Medicine.

Schizophrenia is a neurological brain disorder that affects 2.2 million Americans today. The disease is usually first diagnosed in adolescents and young adults.

The 2001 Academy Award winning movie "A Beautiful Mind" depicted the life of Nobel laureate John Forbes Nash Jr., a brilliant mathematician who fought the disease throughout his life. The hallmarks of schizophrenia include delusions, hallucinations and difficulty managing emotions and making decisions.

Direct and indirect costs of schizophrenia are estimated at more than $32 billion a year in the United States.

"Schizophrenia is a very difficult disease to treat," said Dr. Leslie Citrome, professor of psychiatry at the New York University School of Medicine in New York City. "I was surprised that olanzapine came out ahead of the other drugs as far as efficacy was concerned. I think most psychiatrists believe that all these drugs were about the same in treating patients."

In the trial, patients from 57 institutions were enrolled to receive doses of four of the atypical anti-psychotics, newer drugs that have fewer of the movement disorder side effects often seen with the older, conventional, anti-psychotics, such as the one selected in this trial, perphenazine.

Perphenazine appeared to have similar efficacy as the other medications, the researchers said.

The primary goal of the study was to determine how many patients would remain on treatment.

"Stopping or changing medication is a frequent occurrence and major problem in the treatment of schizophrenia," Lieberman said in the journal article, which was released early, following a news briefing in Boston on Monday, due to interest in the study.

Of the 330 patients on olanzapine, 188 or 64 percent stopped taking the medication before the end of the trial -- 48 who complained of lack of efficacy, 62 who complained of adverse clinical events and 78 because the patients just decided to stop. The patients' decision to stop the drug was the single major reason for discontinuation in each of the five patient groups.

"Exploring why they decided to stop could be enlightening," Citrome told United Press International. He said many patients who decide to stop taking the medication complain they just do not feel good taking it.

Other patients may reason that because they feel better, they no longer need to take the medication, he said, adding there may be other reasons that can be identified.

Only 26 percent of the 33 patients on risperidone were able to complete the trial, along with only 25 percent of the 257 patients on perphenazine, 21 percent of the 183 patients on ziprasidone, and 18 percent of the 329 patients on quetiapine.

Citrome suggested that the study, the largest of its kind ever performed, will become a boon for marketing strategies. In clinical practice, "doctors will still have to evaluate patients one by one, considering effectiveness, costs, and tolerability. All these drugs and their impacts vary from patients to patient," he said.

"Even when we looked at weight gain, often seen in olanzapine," Citrome said, "There was great variability among those who were taking the drug," he said. "There were a few people who actually lost weight -- 1.4 pounds a month -- on olanzapine, and there were others who gained as much as 9.5 pounds a month."

The study did not evaluate the latest anti-psychotic on the market, aripiprazole -- marketed as Abilify by Bristol-Myers Squibb -- or other drugs in development, said Dr. Robert Freedman, chairman of the department of psychiatry at the University of Colorado Health Sciences Center in Denver, in an NEJM editorial. "How these drugs perform in comparison with olanzapine is unknown."

The CATIE study was performed under the guidance and funding of the National Institute for Mental Health, a division of the National Institutes of Health.

Citrome said clinicians could give more weight to the study because of its government funding when deciding which drug is best for their individual patients, relegating less importance to trials sponsored by the manufacturers.

The Foundation of Hope in Raleigh, N.C., provided additional funding, and the pharmaceutical companies provided drugs for the study.

"The value of CATIE," Freedman said, "is that it provides solid evidence to help clinicians and their patients make the difficult decisions needed to optimize the treatment of schizophrenia with the compounds currently available."

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Ed Susman covers medical research for UPI. E-mail: sciencemail@upi.com