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The Risk of Unintended Consequences

Oldham, John, MD

Journal of Psychiatric Practice®: November 2005 - Volume 11 - Issue 6 - p 359
From the Editor


November, 2005. The much-anticipated first results of the NIMH-funded landmark Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study have been published and have justifiably generated a great deal of interest.1 Patients with schizophrenia were randomized to receive one of four second generation antipsychotics (SGAs)-olanzapine, quetiapine, risperidone, or ziprasidone, or one first generation antipsychotic (FGA)-perphenazine, and the patients were followed for 18 months. The main outcome measure was time from intake until a patient discontinued the medication, because of insufficient efficacy, side effects, or other reasons. Among the results of the study were the findings that all five medications produced improvement in patients, and that those on olanzapine fared a bit better. However, rates of discontinuation of medication during the 18 months ranged from 64% to 82%. In an editorial accompanying the article,2 Freedman stated that the "results could be viewed as discouraging. No drug provided the majority of patients a treatment that lasted the full 18 months of the study" (p. 1,287). Furthermore, the one drug that was somewhat more effective in controlling symptoms, olanzapine, was associated with significant weight gain and diabetes. Nonetheless, while it would have been welcome to see more robust improvement from, and adherence to, all of the medications, the study is enormously informative and helps practitioners individualize treatment for a given patient, weighing potential risk and benefit in the context of the patient's history and risk profile.

Interestingly, a widespread response to these results, in the category of unintended consequences, has been the cry from budget-builders, insurers, and formulary planners that the older and cheaper medication has now been shown to be as effective as the newer ones. In fact, the results are far more complex than that; for example, only one FGA was studied, patients with known prior risk for tardive dyskinesia were excluded from treatment with perphenazine, and the high discontinuation rates limited information about the development of longer term side effects. It is crucial that important research findings such as these not be inappropriately and inaccurately added, by those who control the purse strings, to the already heavy burdens endured by our most disabled patients.

In this issue of the Journal, Burton reviews strategies to improve adherence to SGAs, a subject of great concern, as clearly demonstrated by the CATIE study. Also in this issue, Richardson et al. report the effects of increasing "lifestyle physical activity" in patients with depression and other serious mental illnesses, including schizophrenia. One result of this program, weight loss, has numerous benefits, and of course it helps counteract some of the most vexing side effects of the treatments that work.

John Oldham, MD


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1. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Eng J Med 2005;353:1209-23.
2. Freedman R. The choice of antipsychotic drugs for schizophrenia. N Eng J Med 2005;353:1286-8.
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