The NIMH-CATIE Schizophrenia Study: What Did We Learn?

Abstract

It has been over 10 years since the initiation of the National Institute of Mental Health (NIMH) Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and 5 years since the first publication of its primary results (1). In this period, the initial report has been cited in the literature over 1,600 times (2) while more than 80 articles from the study’s extensive database (Table 1), as well as a book serving as an archive of the study’s results and implications (3), have been published. In the meantime, several more randomized trials comparing the effectiveness of antipsychotics have been completed (4–6), meta-analyses that bear on the findings of the CATIE study have been performed (7, 8), and commentaries on CATIE’s findings and critiques of its methodology have been published (9–11). All of these help us to view the CATIE study in a broader context and enable us to determine what we really learned from it. When the CATIE study was designed in 1999– 2000, the prevailing opinion of researchers and clinicians alike was that the newer (second-generation) antipsychotic drugs were vastly superior to the older (first-generation) antipsychotic drugs in efficacy and safety. This largely reflected the results of studies sponsored by the manufacturers of the new drugs (12, 13), marketing messages of pharmaceutical companies and the hopes of many who wanted better treatments. Indeed, the hypothesis and expectation of the CATIE study investigators was that the firstgeneration antipsychotic perphenazine would be inferior to the newer agents. Consequently, the finding that perphenazine was similar in effectiveness to most other medications had a profound effect that extended beyond the scientific and psychiatric communities to the lay public and various stakeholder groups. Somewhat sensational news reports decried the preferential use and greater cost of the newer medications and the marketing practices that led to them. For example, the September 21, 2005, editorial page of The New York Times opined, “A government-financed study has provided the strongest evidence yet that the system for approving and promoting drugs is badly out of whack. The study compared five drugs used to treat schizophrenia and found that most of the newest, most heavily prescribed drugs were no better than an older drug that is far cheaper. The nation is wasting billions of dollars on heavily marketed drugs that have never proved themselves in head-to-head competition against cheaper competitors” (14). But what did we really learn from the CATIE study? In this commentary, we summarize its major implications and their relevance to clinical practice. We will also address some of the study’s most relevant critiques.