A recent study comparing medications used to treat schizophrenia
is the latest example of an emerging type of large-scale clinical
effort aimed at finding the most effective ways to treat chronic
conditions. Such studies are particularly important as the burden
of chronic diseases grows and medical costs continue to soar. The
surprise in this study is that the older treatments, which are
less expensive than newer ones, may be just as good. It isn't the
first study of this type to reach that conclusion.
Schizophrenia is a chronic, recurrent mental illness that brings
hallucinations, delusions and disordered thinking to 3.2 million
Americans. Antipsychotic drugs were first discovered and used to
treat the disease in the 1950s, and increasingly potent drugs with
different side effect profiles have been emerging ever since. Second-generation
drugs called "atypical" drugs have been touted as being as effective
as older drugs while causing fewer side effects. Although the evidence
for that hasn't been solid, they now have a 90 percent share of
the U.S. market despite being roughly 10 times more expensive.
The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness)
trial was launched by NIMH to compare the effectiveness of antipsychotic
drugs. The 18-month study involved more than 1,400 participants
at 57 clinical sites around the country. Researchers directly compared
an older medication, perphenazine, available since the 1950s, to
four newer medications: olanzapine, quetiapine, risperidone and
ziprasidone. Their primary outcome measure was discontinued treatment,
a definable outcome integrating many factors, including doctors' and
patients' judgments about efficacy and side effects, and encompassing
real-world complications. Stopping or changing medications is common
in people with schizophrenia, so it's a particularly relevant measure.
Unfortunately, none of the drugs lasted the full 18 months of
the study for most of the patients taking them. Only 36 percent
of those taking the most effective drug, olanzapine, completed
the trial. The differences between olanzapine and perphenazine,
the older medication, were moderate, and the results for the other
atypical drugs were comparable to perphenazine. Olanzapine might
therefore seem the best of the antipsychotic drugs at first glance,
but patients in the olanzapine group gained an average of 2 pounds
per month, more than patients in any other group, and had blood
glucose, cholesterol and other measures signaling the development
of metabolic syndrome-a serious health condition.
There's clearly a complex series of trade-offs between efficacy,
side effects and price among these drugs and this study will help
people make more informed decisions about them. Future CATIE reports
will address cost-effectiveness, quality of life and other aspects
of these medications. CATIE, NIMH says, is part of an overall effort
to conduct "practical" clinical trials that address public health
issues. It brings to mind NHLBI's ALLHAT (Antihypertensive and
Lipid-Lowering Treatment to Prevent Heart Attack Trial), which
compared three major classes of medications to treat high blood
pressure and found that less costly diuretics are at least as effective
as higher-priced drugs.
Given the high costs of health care, these types of head-to-head
comparisons will be critical for delivering better, more cost-effective
care. 
