Sep 20, 2005 01:00 AM

Page A01

Expensivenew antipsychotic drugs that are among the most widely prescribed pillsin medicine are no more effective and no safer than an older, cheaperdrug that has been largely discontinued, according to the mostcomprehensive comparative study ever conducted.

The surprisingresult of a federally funded study released yesterday challengeswidespread assumptions among psychiatrists about the best way to treatserious mental illness and underscores the extent to which physicians,patients and policymakers can be blindsided by self-interested researchby drugmakers.

The study also paints a sobering picture of thestate of treatment of schizophrenia, a disabling illness that afflictsabout 3.2 million Americans with symptoms such as delusions,hallucinations and disordered thinking: Every drug, old and new, causedserious side effects, and the vast majority of patients stopped takingeach of them.

“The study has vital public health implications,”said Thomas Insel, director of the National Institute of Mental Health,which funded the study. “It is the largest, longest and mostcomprehensive, independent trial ever done to examine existingtherapies for this disease.”

Heavily marketed on the groundsthey caused fewer side effects, the newer drugs, known as atypicalantipsychotics, cornered about 90 percent of the market.

All wonFood and Drug Administration approval on the basis of short-termstudies that showed they were better than sugar pills, and researchersemphasized yesterday that the medicines do work. But they have neverbefore been systematically compared against each other in a long-termtrial designed to guide doctors in deciding which to try first, andwhich would best suit particular patients.

The new study trackedpatients for 18 months, which allowed researchers to compare theeffectiveness of the medications as they actually are used. Patientshad a variety of complicating factors, much as they do in the realworld, and came from diverse backgrounds.

Columbia Universitypsychiatrist Jeffrey Lieberman, who led the new study, said 90 percentof trials in the scientific literature — which doctors rely on toguide treatment — are sponsored by drug companies. Although theindustry trials serve a useful purpose, he said, they are rarelydesigned to answer certain crucial questions.

The industry hasrecently come under fire for hiding unfavorable trial data, especiallyin studies of antidepressant medications for children. Companiesconduct trials to win FDA approval or for marketing reasons, Liebermansaid.

“These are not the same purposes that are consistent withthe needs of clinicians, patients, family members, administrators andpolicymakers,” he said. “How do currently marketed treatments compare?If there are differences in cost, are they justified? There has notbeen any consistent means to get that information.”

Although theNational Institutes of Health is increasingly funding such trials,Lieberman said they also ought to be funded by federal agencies thatpay for drug treatment for huge numbers of patients, such as theCenters for Medicare and Medicaid Services (CMS).

“CMS pays tensof billions to support medication, and there is no way they know whatthe appropriate value of these medications is,” he said.

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

Lieberman andthe other researchers said they were surprised to find that an oldergeneric drug called perphenazine, which is 10 times cheaper than thenewer drugs, was about as effective — and about as safe.

Olderantipsychotics are known to cause involuntary muscle movements, and thenewer drugs were heralded for not causing that problem. But Liebermansaid comparisons with older drugs had mostly used a highly potent drugcalled Haldol, whereas the new study did not find the same degree ofmovement problems with perphenazine, a less potent drug.

In aneditorial accompanying the study, Robert Freedman, a psychiatrist atthe University of Colorado Health Sciences Center, said theuncontrolled movements caused by the older drugs were “less troublingthan potentially fatal metabolic problems” associated with some of thenewer drugs.

Yale psychiatrist Robert Rosenheck, who helpedconduct the study, said it was “not a horse race” that produced awinner. Rather, he said, each drug had benefits and risks. Doctors willhave to judge what works best for particular patients.

“It wouldbe a tremendous mistake to assume from this study that the cheaper,older drugs are, quote, ‘just as good,’ ” added Darrel Regier, directorof the division of research for the American Psychiatric Association,who also said that doctors’ judgment is crucial.

The study islikely to stoke one of the most contentious debates in psychiatry –whether drug treatment ought to be forced on unwilling patients. Thefact that three-quarters of patients discontinued treatment because ofside effects or a lack of benefit showed that patients “trying to sayno to forced neuroleptics [drugs] have had a better grip on realitythan the medical community,” said David Oaks, a patient advocate whohas himself been given five antipsychotic drugs at various times for arange of diagnoses, including schizophrenia.

Pharmaceuticalcompanies called attention to aspects of the trial that showed theirproducts to advantage. Geodon kept patients’ weight gain andcholesterol down, said Pfizer’s Daniel J. Watts. Zyprexa had a lowerdiscontinuation rate, manufacturer Eli Lilly said. The dose ofRisperdal used in the study was too small, which was why the drug didnot work as well as it should have, said Ramy A. Mahmoud, vicepresident for medical affairs at Janssen Pharmaceutica Inc.

AlanGoldhammer of the Pharmaceutical Research and Manufacturers of America,said, “We have always made it clear during drug development that it isonly the first stage, that it . . . never tells the whole story aboutsafety and efficacy.”

Large studies, which compare differentdrugs including generics, are beyond the capabilities of individualcompanies, he said: “They are so costly and time-consuming that itwould probably bring drug development to a halt.”

Patientadvocate Vera Hassner Sharav, who said her son died at 32 because oftoxic side effects associated with the antipsychotic drug Clozaril,said the new study showed that the FDA is not doing its job. “We reallyonly seriously test drug safety on the vast public,” she said. “That isnot right.”

– end of _Wash. Post_ article –

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[Here’s the full statement MindFreedom submitted to the Washington Post, resulting in the quote in the above article.]

Challenging fraudulent claims about “atypical neuroleptic” psychiatric drugs

Statement by David Oaks, Director, MindFreedom International

Ihave heard zealots lobby for a massive increase in involuntarypsychiatric drugging by claiming that the newer neuroleptics are farmore effective and that the side effect nightmare that plagued olderneuroleptics had been solved.

But this new federal study showsthat many of our members who have been desperately trying to say “no”to forced neuroleptics have had a better grip on reality than themedical community.

The drug industry hype about miracle wonderpills turns out, once more, to be fraud. The drug industry hasseriously mis-informed the public, the medical community, governmentdecision-makers, families and patients. This fraud has caused serioussuffering among a very marginalized group. The bizarrely high costs ofthese drugs threaten to bankrupt many state and local health caresystems.

The New England Journal of Medicine official editorialwarns that patients face “difficult choices” about drugs that canpotentially cause “fatal metabolic problems” and therefore the answeris “informed patient preference.” But when the rubber hits the road,patients and their families are routinely lied to about efficacy andhazards of these drugs, and far too many patients are forced andcoerced to take neuroleptics, including with court orders on anoutpatient basis in their own homes.

And of course, families in crisis are seldom offered humane and safe alternatives to psychiatric drugs.

Ihave personally experienced forced neuroleptics and the experience canfeel overwhelmingly horrible, a profound intrusion of our basic humanrights, like a wrecking ball to the mind. That qualitative experiencedoesn’t tend to get out in these studies.

The controversy hereis beyond being pro or con drugs. Some of our members willingly chooseto take prescribed psychiatric drugs. The issue is really aboutfreedom. And the drug corporation domination threatens basic humanrights in our society.

The big picture is what we at MindFreedomcall the take-over of the mental health system by the drug industry,which impacts research, conferences, medical associations and choice oftreatments.

While it’s good to see a study focus on efficacy andside-effect problems such as weight gain and diabetes, the biggeststory that the public hasn’t heard yet is that taking long-termhigh-dosage neuroleptic is associated with actual structural damage tothe higher level parts of the brain. These brain changes can make itvery difficult to quit neuroleptics by creating dependence.

Itwould also be good to see far more studies about non-drug alternativesthat have been shown to be effective, safer and more sustainable,especially ten, twenty or thirty years down the road. A corerecommendation of President Bush’s New Freedom Commission was morestudy of the long-term effects of psychiatric drugs but we haven’t seenthat happen yet.

A drug-based approach to psychiatric problemsis also poised to globalize as never before. There ought to be open,honest and public debate about these questions to prevent that fromhappening. It’s time for democracy to get informed and hands-on withthe mental health system.

After thirty years of watching thepsychiatric drug industry I’ve come to see it as a traveling medicalshow. Whenever their current approach is finally debunked they alreadyhave a load of new drugs waiting in the pipeline. We expect to see anumber of new neuroleptics produced in the next few years and thepublic’s skepticism ought to be on high alert.

– end statement –