In Antipsychotics, Newer Isn't Better

By Shankar Vedantam
Washington Post Staff Writer
Tuesday, October 3, 2006

Schizophrenia patients do as well, or perhaps even better, on older psychiatric drugs compared with newer and far costlier medications, according to a study published yesterday that overturns conventional wisdom about antipsychotic drugs, which cost the United States $10 billion a year.

The results are causing consternation. The researchers who conducted the trial were so certain they would find exactly the opposite that they went back to make sure the research data had not been recorded backward.

The study, funded by the British government, is the first to compare treatment results from a broad range of older antipsychotic drugs against results from newer ones. The study was requested by Britain's National Health Service to determine whether the newer drugs -- which can cost 10 times as much as the older ones -- are worth the difference in price.

There has been a surge in prescriptions of the newer antipsychotic drugs in recent years, including among children.

The study, published in the Archives of General Psychiatry, is likely to add to a growing debate about prescribing patterns of antipsychotic drugs. A U.S. government study last year found that one of the older drugs did as well as newer ones, but at the time, many American psychiatrists warned against concluding that all the older drugs were as good.

Yesterday, in an editorial accompanying the British study, the lead researcher in the U.S. trial asked how an entire medical field could have been misled into thinking that the expensive drugs, such as Zyprexa, Risperdal and Seroquel, were much better.

"The claims of superiority for the [newer drugs] were greatly exaggerated," wrote Columbia University psychiatrist Jeffrey Lieberman. "This may have been encouraged by an overly expectant community of clinicians and patients eager to believe in the power of new medications. At the same time, the aggressive marketing of these drugs may have contributed to this enhanced perception of their effectiveness in the absence of empirical information."

Peter Jones, a psychiatrist at the University of Cambridge in England who led the study, searched yesterday for the right word to describe what had happened to his colleagues.

" 'Duped' is not right," he said. "We were beguiled."

One drugmaker immediately questioned the findings. Carole Puls, a spokeswoman for Eli Lilly and Co., which makes Zyprexa, said it was problematic to compare large groups of medications because there are differences between the drugs in each class. Individual patients need different medication options, she said.

Janssen Pharmaceutica, which makes Risperdal, and AstraZeneca, which makes Seroquel, did not respond to requests for comment.

Schizophrenia is a serious mental disorder that is believed to affect about one in 100 adults. It is characterized by psychotic symptoms such as hallucinations and delusions and negative symptoms such as social withdrawal.

Especially over the past decade, older antipsychotics such as Haldol have been widely criticized for triggering uncontrolled body movements, even as the new "atypical" antipsychotics were hailed for causing fewer side effects. Recently, however, concern has grown that antipsychotics in general, and some of the newer drugs in particular, may be causing metabolic side effects.

The new study randomly assigned 227 schizophrenia patients to two groups -- one received a newer antipsychotic, the other an older drug. The patients were evaluated for more than a year by experts who did not know which drug was being taken.

While the researchers had expected a difference of five points on a quality-of-life scale -- showing the newer drugs were better -- the study found that patients' quality of life was slightly better when they took the older drugs. Jones said a conservative interpretation of the data suggested that there is no difference, "so the notion you would pay 10 times as much would be difficult to justify."

"Why were we so convinced?" he asked, referring to the widespread opinion among psychiatrists that the new drugs were worth the great difference in cost. "I think pharmaceutical companies did a great job in selling their products. That is certainly one issue.

"It became almost a moral issue on whether you would prescribe these dirty old drugs," he added. "It became the 'my son' phenomenon. What would you prescribe for your son?"

In retrospect, Jones and others said, there were hints going back many years. In 2003, Robert Rosenheck, a psychiatrist at the Department of Veterans Affairs, found there was no difference between Haldol and Zyprexa -- after patients taking Haldol were treated to prevent the movement side effects.

Last year, the U.S. government trial found that an older drug called perphenazine did about as well as the newer medications. Still, the belief in the newer drugs was so ingrained that many psychiatrists insisted that the results could not be extrapolated to other old drugs, said Rosenheck, who helped conduct that study.

Darrel Regier, who directs research at the American Psychiatric Association, cautioned against drawing broad conclusions after the new study and said that "a thoughtful and prolonged process " is needed before treatment guidelines are changed. Not all the drugs used in the British study were available in the United States, he said, and with many of the newer medications reaching the end of their patent lives, he predicted that questions of cost would fade away.

Jones and Rosenheck said the problem with many drug company studies that seemed to show that new drugs are better is that they focused on short-term results -- a symptom or side effect -- rather than the big picture: how patients fare long-term.

"The story of these newer antipsychotic drugs is a story that reveals an institutional gap," Rosenheck said. "It should not have needed 10 years to get three government studies."

Jones said the studies also illustrate the importance of trusting data, rather than judgment. He drew an analogy with his hobby of walking.

"Sometimes the compass tells you go straight in front of you, but you somehow know it is wrong and that north is behind you," he said. "I have learned to follow the compass."

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