The controversy over whether the high costs of second-generation
antipsychotics (SGAs) are associated with significant benefits that justify
prescribing them rather than cheaper first-generation antipsychotics (FGAs) is
the subject of the cost-effectiveness analysis from the National Institute of
Mental Health-sponsored CATIE (Clinical Antipsychotic Trials of Intervention
Effectiveness) study, reported in the December American Journal of
Psychiatry (see story beginning on page 1.
However, the usefulness of the report is challenged by an accompanying
editorial, signed by AJP Editor in Chief Robert Freedman, M.D., and
cosigned by schizophrenia and antipsychotic medication experts William
Carpenter Jr., M.D., and John Davis, M.D.; and Howard Goldman, M.D., Ph.D. (an
AJP associate editor), Carol Tamminga, M.D. (an AJP deputy
editor), and Marshall Thomas, M.D.
In their editorial, they noted that the CATIE investigators"
carefully avoid clinical recommendations, but the results suggest
significant economic benefits of cheaper first-generation medications without
any significant decrement in the overall clinical effect."
That conclusion is sure to spark debate, and a range of reactions will
likely be elicited by the editorialists' remarkable disclosure that "the
study has limitations that became apparent during its peer review at the
Journal.... We decided to publish the paper, despite serious
reservations, because there are important lessons to be learned from
The 18-month study was too short, they wrote, "for the lifetime of
care for schizophrenia," thus too short a time to pick up on long-term
adverse events, such as tardive dyskinesia or metabolic syndrome, that vary
among the drugs studied.
Second, they questioned the methods used to assign medications, noting that"
the restriction of perphenazine [assignment] to patients who did not
have tardive dyskinesia limits randomness."
Third, they questioned the CATIE investigators' decision to present an
intention-to-treat analysis. "The comparison of costs by initial
treatment assignment when patients did not continue on the same treatment for
the entire study has an uncertain value."
It was the lack of overall difference in Quality Adjusted Life Year (QALY)
ratings favoring SGAs, however, that the AJP editorialists noted was"
most troubling to the reviewers.... Failure to find difference does not
mean that there is no difference," they stressed. It might mean that"
methods are too crude to demonstrate differences that may nonetheless
be important for patients." The study findings, they added, may"
indicate differences in the effects of some drugs that are clinically
relevant, even if they are not captured in the QALY analysis."
Most important of "the lessons learned" is the calculation of
lower costs for perphenazine and the ability to see "how much the costs
of treatment for chronic schizophrenia are driven by the costs of the
Most disappointing, the editorialists said, is the notion that hundreds of
millions of dollars and many years were spent to give clinicians and patients
a new generation of "better" medications. Yet the new drugs appear
to be no more effective than some earlier ones, and CATIE clearly showed that"
the side effect burden has shifted, not disappeared."
"The Costs of Drugs for Schizophrenia" is posted at<www.ajp.psychiatryonline.org>
under the December issue.