The US spends more than $200 billion annually on prescription drugs, yet 'we have no idea what the relative effectiveness of these drugs are compared to each other,' says the lead author of the research.

The cost of the NIMH study is high -- $45 million -- but experts say it could pay for itself many times over if it leads to a significant reduction in the $10 billion now spent annually on drugs for the nation's 3.2 million schizophrenics.

"The implication of this study is that we've been wasting billions of dollars a year on drugs that have either no or minimal benefit over the older ones, or that have minimal advantages that are greatly outweighed by their side effects," said Dr. Daniel Luchin, a University of Chicago psychiatrist who was not involved in the study.

Perphenazine Just as Effective

Reporting in Monday's online edition of the New England Journal of Medicine, researchers headed by Columbia University's Dr. Jeffrey Liberman found that the older drug, Trilafon (perphenazine), was just as effective as three newer antipsychotics, Seroquel (quetiapine), Risperdal (risperidone) and Geodon (ziprasidone).

A fourth drug, Zyprexa (olanzapine), was somewhat better at controlling the hallucinations, delusions and disordered thinking that characterize the disease, but it carried a greater risk of type 2 diabetes and other metabolic changes.

For more than a decade the federal Food and Drug Administration has relied on drug firms to test their own drugs for safety and effectiveness. Typically a company compares a new drug with a dummy pill to see if the new compound is more effective than an inert substance. Ninety percent of new drug studies are conducted by the pharmaceutical industry.

But a growing number of medical experts say the way drug companies test new drugs is inadequate and self-serving. What are needed, they contend, are more studies like the one conducted by NIMH that compare new drugs head to head with existing medications for the same disorder.

"These kinds of data are most important because they give doctors information that they didn't have before that help them to make the choices about what drug should be used in any given patient," said NIMH director Dr. Thomas Insel.

More Drug Comparisons Needed

The problem with studies conducted by pharmaceutical companies, Insel said, is that they are short term and involve a relatively small number of the healthiest patients.

The 18-month NIMH study, on the other hand, involved 1,400 patients treated in real-world settings at 57 sites that included doctors' offices, community clinics and hospitals.

"The pharmaceutical industry does studies comparing new drugs to placebos to get FDA approval," Liberman said. "Clinicians could care less. They want to know how the drug works compared to other medications. So, unless you have a study that's looking at all the drugs in the same study, and for a long enough period of time and using the appropriate measures of assessment, you can't know."

The nation spends more than $200 billion annually on prescription drugs, yet "we have no idea what the relative effectiveness of these drugs are compared to each other," Liberman said. "These kinds of studies are essential given the investment that our society is making in these treatments."

Alan Goldhammer, associate vice president for regulatory affairs for Pharmaceutical Research and Manufacturers of America, said the National Institutes of Health are in the best position to conduct large studies comparing drugs.

Pharmaceutical companies have limited resources and to undertake this kind of study would mean diverting funds devoted to discovering new drugs, he said.

"The FDA operates on a standard of showing safety and efficacy for the drug under conditions of use," Goldhammer said. "The requirements are not to do a comparative trial or to evaluate it again unless there's an issue of ethics involved."

Schizophrenia Drugs Are Not a Cure

Use of the older family of antipsychotic drugs, including perphenazine, had decreased because doctors assumed that newer medications would have fewer side effects, especially tardive dyskinesia, which is marked by Parkinson's-like symptoms.

The NIMH study suggests that is not the case.

"We had assumed there would be a huge difference in the rate of extra side effects between the old drug and the new ones," Insel said. "The bottom line is that there's not a huge difference between any of them. There may be a difference in cost and there may be a difference in some side effects, but there's not a huge difference in effectiveness."

Before the first antipsychotic drugs were developed in the mid-1950s, most people with schizophrenia were either confined to mental hospitals or prisons.

Although the available drugs control symptoms to the point where most patients can function to some degree, they are not a cure and much better medications need to be developed, Insel said.