Dec. 1 (Bloomberg) -- 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