Questioning Drug Costs In Schizophrenia Treatment

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 it.”

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 drugs.”

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.