Cost Benefits of New Schizophrenia Drugs Doubted
Older Medication, Considered Equally Effective, Can Be
as Much as $600 a Month Cheaper, Study Finds
By Shankar Vedantam
Washington Post Staff Writer
Friday, December 1, 2006; A09

Treating schizophrenia with an older, cheaper drug,
rather than with heavily promoted newer medications,
reduces the cost by as much as 30 percent with no
apparent difference in safety and effectiveness,
according to the first study to examine the economic
implications of antipsychotic drug prescribing
practices in the United States.

The newer drugs, such as Zyprexa, Seroquel and
Risperdal, have cornered the lucrative U.S. market for
antipsychotic drugs at a cost of $10 billion a year --
or around $100 for every family.

The findings have roiled the field of psychiatry in a
fierce debate over the study's implications and have
triggered concerns it could lead public and private
insurers to limit drastically which drugs they will
pay for.

Earlier research had shown that the older drug was as
safe and effective as the newer medications. But
experts cautioned against assuming that the cheaper
drug would be as cost-effective once hospitalizations,
side effects and quality-of-life issues were taken
into account.

The new study, published today in the American Journal
of Psychiatry, concluded that when those factors were
included, monthly costs per patient were $300 to $600
lower with the drug perphenazine, which is no longer
under patent. The finding is the latest result from
the $42 million Clinical Antipsychotic Trials in
Intervention Effectiveness (CATIE), a federal study
into the treatment of schizophrenia.

In an indication of the widespread unease in the
psychiatric establishment over the results , one
senior doctor who helped conduct the study but not the
cost-effectiveness assessment said the new finding
faced stiff headwinds before it was published, and was
subjected to an extraordinary level of review.

"You are saying perphenazine is $500 cheaper," said
the doctor, who spoke on condition of anonymity
because of the sensitivity of the issue , to explain
why many psychiatrists weighing the study seemed
aghast. "Now the physicians feel defensive, because
people will ask, 'Why are you charging the patient and
insurance company $500 more when the drugs don't give
you anything more?' "

This doctor, the study's authors and several leading
psychiatric experts, including Thomas R. Insel,
director of the National Institute of Mental Health,
emphasized that the study does not mean that patients
doing well on more expensive drugs should be switched
to cheaper medication. Switching drugs involves
potential problems, and patients doing well on a drug
should be kept on it, they said .

But because many patients with schizophrenia need to
change medications frequently -- an earlier part of
the study found that three-quarters of patients
discontinue whatever drug they are on within 18 months
-- many could become candidates for treatment with the
less expensive drug in a short period of time.

"If they are chronically ill and are not on medication
or want to switch, it is certainly a rational choice
and would save money, and for the most part we can't
detect effectiveness differences," said Robert
Freedman, editor in chief of the journal, who co-wrote
an editorial accompanying the study.

Freedman and several experts said they were very
worried, however, that the choice of medications would
be taken from physicians and would be decreed by
insurers. That would ignore the complexities of
treating schizophrenia and the need for flexibility,
the experts said.

Patients who have tried perphenazine unsuccessfully,
for example, may not be good candidates to go back on
it. The federal study looked only at people who had
had schizophrenia for a long time, not newly diagnosed
patients. And overall, the fact that patients are
dissatisfied so often with medications, including
perphenazine, means that flexibility remains key.

In statements, drugmakers AstraZeneca, which makes
Seroquel, and Eli Lilly and Co., which makes Zyprexa,
said patients benefit from having individualized
treatment. The federal Centers for Medicare and
Medicaid Services -- Medicaid picks up three-quarters
of the $10 billion tab for antipsychotic drugs -- also
believes that physician discretion is essential, a
spokesman said.

Drug-industry critic Jerry Avorn, author of the book
"Powerful Medicine: the Benefits, Risks, and Costs of
Prescription Drugs" and a professor of medicine at
Harvard Medical School, said this is not a case of
difficult trade-offs between cost and quality.

"The cheapest drug produced an effect that was as good
as the more expensive drugs," he said. "The resistance
to this kind of finding comes from . . . the very
legitimate worry that boneheaded cost containers will
read this study and then try to get every
schizophrenic on every other medication to be switched
to the cheapest available product. I am a proponent of
educating doctors first rather than tying our hands."

Both Insel and Robert Rosenheck, the Yale University
psychiatrist who led the cost-effectiveness study,
said the message was not that the half-dozen expensive
new drugs should be replaced by perphenazine. Rather,
they said, the message of the CATIE study is that once
a range of side effects is taken into account, many
older antipsychotic drugs may have risks and benefits
that are similar to those of the newer drugs.

"It triples the size of the antipsychotic
armamentarium available to psychiatrists," Rosenheck
said. "Before CATIE, we had five to six drugs and we
had tremendous pressure to not use the other 15. What
CATIE has said is doctors should feel free to use
whatever medicine is right for their patient, and
there are 19 or 20 choices, not five or six."

Although both old and new classes of drugs have
similar effectiveness in controlling symptoms such as
delusions and hallucinations, the advent of the newer
drugs was hailed because they seemed less likely to
cause side effects involving involuntary muscle
movements.

But evidence has gradually accumulated that the newer
drugs do cause weight gain and serious metabolic
problems. Essentially, the editorial noted, the new
medications have resulted in a change in side effects,
rather than eliminating them.

Rosenheck said the study means that patients paying
for expensive new drugs out of pocket who wanted to
switch could try perphenazine without the concern that
they are getting inferior treatment. The magazine
Consumer Reports recently listed perphenazine, which
is sold as a generic drug, as a "best buy" among
antipsychotics.

While Rosenheck and CATIE lead scientist Jeffrey
Lieberman of Columbia University disagreed with the
authors of the editorial on how to interpret several
aspects of the study, everyone agreed that the trial
provides the best window in the country to date on the
treatment of schizophrenia. The editorial said the
study highlighted the need for new and better
treatments -- and perhaps a new and better mechanism
of financial rewards to spur their development.




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