New Antipsychotic Drugs Criticized

The new study, which will be published in the New England Journal of Medicine, cost taxpayers $44 million. Last year, the United States spent $10 billion on the newer antipsychotic drugs, which include medications such as Zyprexa, Risperdal, Seroquel and Geodon.

Lieberman and the other researchers said they were surprised to find that an older generic drug called perphenazine, which is 10 times cheaper than the newer drugs, was about as effective -- and about as safe.

Older antipsychotics are known to cause involuntary muscle movements, and the newer drugs were heralded for not causing that problem. But Lieberman said comparisons with older drugs had mostly used a highly potent drug called Haldol, whereas the new study did not find the same degree of movement problems with perphenazine, a less potent drug.

In an editorial accompanying the study, Robert Freedman, a psychiatrist at the University of Colorado Health Sciences Center, said the uncontrolled movements caused by the older drugs were "less troubling than potentially fatal metabolic problems" associated with some of the newer drugs.

Yale psychiatrist Robert Rosenheck, who helped conduct the study, said it was "not a horse race" that produced a winner. Rather, he said, each drug had benefits and risks. Doctors will have to judge what works best for particular patients.

"It would be a tremendous mistake to assume from this study that the cheaper, older drugs are, quote, 'just as good,' " added Darrel Regier, director of the division of research for the American Psychiatric Association, who also said that doctors' judgment is crucial.

The study is likely to stoke one of the most contentious debates in psychiatry -- whether drug treatment ought to be forced on unwilling patients. The fact that three-quarters of patients discontinued treatment because of side effects or a lack of benefit showed that patients "trying to say no to forced neuroleptics [drugs] have had a better grip on reality than the medical community," said David Oaks, a patient advocate who has himself been given five antipsychotic drugs at various times for a range of diagnoses, including schizophrenia.

Pharmaceutical companies called attention to aspects of the trial that showed their products to advantage. Geodon kept patients' weight gain and cholesterol down, said Pfizer's Daniel J. Watts. Zyprexa had a lower discontinuation rate, manufacturer Eli Lilly said. The dose of Risperdal used in the study was too small, which was why the drug did not work as well as it should have, said Ramy A. Mahmoud, vice president for medical affairs at Janssen Pharmaceutica Inc.

Alan Goldhammer of the Pharmaceutical Research and Manufacturers of America, said, "We have always made it clear during drug development that it is only the first stage, that it . . . never tells the whole story about safety and efficacy."

Large studies, which compare different drugs including generics, are beyond the capabilities of individual companies, he said: "They are so costly and time-consuming that it would probably bring drug development to a halt."

Patient advocate Vera Hassner Sharav, who said her son died at 32 because of toxic side effects associated with the antipsychotic drug Clozaril, said the new study showed that the FDA is not doing its job. "We really only seriously test drug safety on the vast public," she said. "That is not right."