Lost In Translation: What We Really Learned From CATIE

One of the most devastating diseases of our time, schizophrenia, is also one of the most con-founding to treat. As the principal investigator on a recent landmark drug trial—a comprehensive, long-term analysis of how to treat schizophrenia, independently funded by the National Institute of Mental Health (NIMH)—I am concerned that the most valuable information learned from this unprecedented study has been “lost in translation” by early reports that focused more on costs and less on the potential for better, more individualized care that this study's findings will enable.

The NIMH Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) study, published in the September 22, 2005, New England Journal of Medicine examined the effectiveness of most marketed antipsychotic medications in 1,500 schizophrenia patients (Psychiatric News, October 21, 2005). These 1,500 patients were monitored under real-world conditions at 57 clinics in 24 states throughout the United States.

We specifically compared newer medications for schizophrenia both with each other and with an older medication. For the first time, we looked not only at how the drugs affected patients' symptoms, but also how they affected patients' overall activities of daily living in dealing with this condition.

How well our patients functioned day to day while on the medications, how many other health care and social support services they needed, and how long they chose to stay on each of the therapies were monitored for a year and half—far longer than in most such studies.

Much of the follow-up reporting of the CATIE study began with headlines announcing some version of “Newer, High-Priced Drugs No Better Than Older, Cheaper Drugs.” Unfortunately, this shorthand didn't capture what we really learned from CATIE: how health care providers can better deploy all the drugs now available to treat schizophrenia and use them individually or in combination to create the kind of customized, individualized patient care that is becoming the distinctly achievable goal of modern medicine.

The 71 physician investigators in our study found that all the medications helped our schizophrenic patients—indeed, all patients vastly improved on medication, more than they would have without therapeutics.

Yet no therapy was ideal; each had advantages and drawbacks. Each differed slightly from the others in terms of effectiveness and side-effect rates. A single doctor in individual practice does not have the opportunity to observe the subtlety of these differences across a broad range of patients, as was possible in the study. Yet that subtlety in effect can make all the difference in the world to the individual patient.

And our focus needs to be on the patient and finding a therapy satisfactory enough to keep the patient using it.

The insights into real-world patient experience gained from the CATIE trial can guide physicians, helping to reduce the frustrating trial and error so characteristic of schizophrenia care. These findings can help fine-tune medication choices. For example, the most effective drug at controlling symptoms also came with the most side effects, weight gain, and diabetes. If I am treating someone whose schizophrenia is particularly difficult to control and who is otherwise at relatively low risk of diabetes, I might select that therapy and then monitor my patient's blood sugar carefully. For another patient who is older and overweight and has a family history of diabetes, I might choose another therapy.

One of the most surprising CATIE findings was that the older medication was comparably effective and no less safe than the newer drugs.

But perhaps CATIE's most important lesson is about what we don't have. Shockingly, we are using the same class of medications to treat schizophrenia in 2005 that we were using in 1955. Some 2.2 million people in the United States alone are affected by schizophrenia—about 1 percent of the population—and we urgently need better medications to treat this disorder.

What's more, we need more large, practical clinical trials like CATIE, evaluating all available therapies against each other (not placebo). It's only through studies like these that we can learn just how effective each new medication is, how it compares with standard therapies in individual patients, and whether it is indeed worth the incremental cost. ▪