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Study drives
antipsychotic drug choices
for schizophrenia
(December
2005 Issue)
By Nan Shnitzler
The first analysis of a major antipsychotic drug study for schizophrenia
found that an older, less expensive medication worked nearly as
well as second-generation agents, although rates of discontinuation
were high for all five drugs studied. Results appeared in the Sept.
22 New England Journal of Medicine.
Funded by the National Institute of Mental Health (NIMH), the $42.6
million Clinical Antipsychotic Trials of Intervention Effectiveness
(CATIE) was designed to compare older and newer drugs, to compare
newer drugs with each other and to evaluate the cost effectiveness
of newer drugs.
The study enrolled 1,493 chronically schizophrenic patients ages
18 to 65 at 57 medical sites around the country. In the double-blind
study, patients were randomly assigned perphenazine (available since
the 1950s), olanzapine, quetiapine, risperidone or ziprasidone (all
introduced in the 1990s) and followed for 18 months.
\Overall, 74 percent of patients discontinued medication before
18 months because of intolerable side effects or failure to control
symptoms. Patients who discontinued their first medication could
receive other medication in succeeding phases of the study. "The
study has vital public health implications because it provides much-needed
information comparing medication treatment options," says NIMH Director
Thomas R. Insel, M.D. in a statement. "It is the largest, longest
and most comprehensive independent trial ever done to examine existing
therapies." Future reports will examine drug cost effectiveness
and go more deeply into the interaction between patient, medication
and outcomes, per the statement.
Much ado has been made about the "shocking" amount of discontinuation,
says study co-author Robert A. Rosenheck, M.D. of Yale University
School of Medicine. If fact, this study showed less. Most studies
only last six weeks, with about 70 percent of patients completing
the study, he says. In this study, more than 80 percent of patients
were still participating after six weeks. Also, half the patients
lasted the full 18 months, although they might have switched medications.
"The study surprisingly found that the new drugs were no better,
in three out of four cases, than an older less expensive drug,"
Rosenheck says. "Bottom line, we spend $10 billion a year on these
new generation drugs and in this very large independent study, their
advantages were not apparent." Newer medications can cost as much
as 10 times more than older ones, per the NIMH statement.
Patients stuck with olanzapine the longest, but it came with significant
heart-threatening side effects including weight gain and increased
cholesterol.
Perphenazine, the conventional agent, compared favorably with the
newer drugs in terms of efficacy. But more patients discontinued
it because of extra pyramidal side effects, despite rating scales
of neurological effects that showed no significant difference between
the older and newer drugs. Researchers acknowledge these results
were a minor mystery.
"That is something slightly inconsistent, and we don't understand
why," says study co-author T. Scott Stroup, M.D., M.P.H., of the
University of North Carolina School of Medicine.
Standardized rating scales are intended to be reliable, objective
measures of the actual severity of symptoms. In this study, subjective
patient behaviors likely contributed to discontinuation, Stroup
says. Researchers hope to understand more when they drill down into
the results. Nevertheless, the performance of perphenazine in the
study means the older drugs can be reasonable options in many cases,
Stroup says.
Andrew E. Budson, M.D., a neurologist at Edith Nourse Rogers Memorial
Veterans Hospital in Bedford, Mass. says he associates perphenazine
with serious extra pyramidal effects. Results of this study might
make him think twice when prescribing second-generation medications,
primarily because of cost.
"The VA in particular is concerned about cost," Budson says.
"Treatment is about individuals; research is about populations,"
Rosenheck says. "It will take time to see how stakeholders react
to this new scientific information."
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