Psychiatry 2007;4(5):21-23
by Elisa F. Cascade; Amir H. Kalali, MD; Jeffrey Lieberman, MD; John Hsiao, MD; Richard Keefe, PhD; and Scott Stroup, MD
Author Affiliations: Ms. Cascade is Vice President, Strategic Research and Safety, Quintiles Inc., Falls Church, Virginia; Dr. Kalali is Vice President, Global Therapeutic Group Leader CNS, Quintiles Inc., San Diego, California, and Professor of Psychiatry, University of California, San Diego; and Dr. Lieberman is the Lawrence E. Kolb Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons, Director of the New York State Psychiatric Institute, and the Lieber Chair of the Lieber Center for Schizophrenia Research in the Department of Psychiatry at Columbia University, New York, New York; Dr. Hsiao is with the adult treatment and preventive interventions branch of the division of services and interventions research at NIMH in Bethesda, Maryland; Dr. Keefe is Associate Professor of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina; and Dr. Stroup is Associate Professor of Psychiatry at the University of North Carolina at Chapel Hill and Adjunct Associate Professor of Social Medicine.
Abstract
We investigated the share of branded and generic antipsychotics before and after the publication of the CATIE results in September, 2005. According to our data, the publication of the CATIE results has had very little impact on new patient starts. To determine the impact of CATIE on use of olanzapine (Zyprexa®) subsequent to first line therapy, we also examined product share for switch/add patients. We found that since the publication of the CATIE results, the use of olanzapine has stabilized, following a decline subsequent to first line therapy, and may potentially be growing very slowly. An expert commentary is provided on the data.
Key words: antipsychotic, CATIE, schizophrenia, olanzapine, zyprexa
Psychiatry 2007;4(5):21-23
Introduction
To determine the long-term effectiveness and tolerability of the newer atypical antipsychotics and a conventional antipsychotic (perphenazine), the National Institute of Mental Health funded the CATIE (Clinical Antipsychotic Trials in Intervention Effectiveness) Schizophrenia Study. Published in the September 22, 2005, issue of the New England Journal of Medicine (and more broadly in the popular press), results from the CATIE study found that the newer atypical antipsychotics (with the exception of olanzapine [Zyprexa®]) had similar discontinuation rates to perphenazine; however, the side effect rate associated with olanzapine (e.g., primarily metabolic) was also the highest among the drugs studied. In this article we examine the results of CATIE on physician prescribing.
Methods
To investigate share of branded and generic antipsychotics before and after the publication of the CATIE results in September 2005, we examined quarterly retail pharmacy prescription data Verispan from January, 2004, through December, 2006. The Verispan data captures more than 1.4 billion patient-centric prescriptions per year, nearly half of all prescription activity in the US. This data set includes prescriptions from a variety of retail channels (e.g., national retail chains, mass merchandisers) from a near-census of US pharmacies. The Verispan retail pharmacy database also captures information from all payer types, including cash.
Results
Figure 1 presents new patient share among branded and generic antipsychotics. As seen in the graphic, the publication of the CATIE results has so far had very little impact on new patient starts. Although there appeared to be a small bump in generic prescribing around the time of publication, the use of generics has now returned to pre-publication levels. Despite the fact that olanzapine was demonstrated to have the greatest efficacy across all agents included in the study, the CATIE publication has had no discernable impact on the trend in first line olanzapine use.
To examine the impact of CATIE on use of olanzapine subsequent to first line therapy, we also examined product share for switch/add patients. As seen in Figure 2, the trend in use of olanzapine among new patients is very different than use subsequent to 1st line (i.e., switch/add patients). In fact, although the decline in olanzapine share subsequent to first line therapy had been slowing, since the publication of the CATIE results in September, 2005, the use of olanzapine has stabilized and may potentially be growing very slowly.
Expert Commentary
by Jeffrey Lieberman, MD; John Hsiao, MD; Richard Keefe, PhD; and Scott Stroup, MD, for the CATIE Investigators Group
Psychiatry 2007’s May “Trend Watch” provides important evidence of the impact that the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project is having on the ongoing debate about atypical antipsychotics and the pharmaceutical industry—although perhaps not quite in the way intended. While there are, of course, two CATIE studies—a trial in chronic schizophrenia comparing atypical antipsychotics to each other and a representative first generation agent and another trial comparing the atypicals to placebo for psychosis and agitation in Alzheimer’s disease—the project did not study use of antipsychotics in other mental health conditions. However, the huge expansion in usage (and cost) of second generation antipsychotics over the past decade has been driven largely by new “indications,” such as bipolar disorder, major depression, and obsessive compulsive disorder.
The data on antipsychotic prescriptions presented in Trend Watch bracket the publication date of the (primary) results from the CATIE schizophrenia trial. During this time, the FDA approved use of quetiapine (Seroquel®) for mania in 2004, then for bipolar depression in 2006, and there were several reports about the weight gain and diabetes risk associated with the atypicals, particularly olanzapine (Zyprexa®). While the CATIE schizophrenia trial found that olanzapine had the greatest efficacy, it also reported that olanzapine had the worst side effects, with significant and substantial differences on weight and metabolic parameters.
Nevertheless, the apparent lack of change in prescription rates reflects the difficulty in changing practice patterns. The publication of data in the scientific literature (to wit; New England Journal of Medicine, American Journal of Psychiatry, and Archives of General Psychiatry) by itself does not necessarily exert large influences on clinical practice despite their veracity. This has been seen repeatedly and may not reflect well on our field. The scientific literature is not the main source of information for the majority of clinicians who may rely on secondary and derivative educational publications and programs or pharmaceutical detail persons, and for whom personal clinical experience outweighs evidence-based medicine—hence the need for educational efforts beyond simple publication of the data to integrate the CATIE results into practice and policy. Indeed, we believe that the focus of the debate has now shifted to process of implementation and policy formation.
Sometimes the question is more important than the answer. What is remarkable about the May “Trend Watch” is that Psychiatry 2007’s editors and readers are asking whether and how the CATIE project has affected clinical practice. The question itself reflects the impact CATIE is having on mental health providers, clinicians, and the pharmaceutical industry. From 1993 to the present, the market share of first generation antipsychotics (based on number of prescriptions) decreased from 90 percent to 10 percent while overall expenditures on (mostly) second generation antipsychotics increased from $1 billion to over $13 billion. The CATIE results call into question how much benefit patients, the mental health system, and society derived from these changes. If clinical practice and prescribing patterns have not yet been impacted, this could be due to a time lag in the process of integrating the CATIE results. It also may be due to the overwhelming impact of a decade and a half of marketing exposures regarding the benefits of atypical antipsychotics for caring clinicians hoping for something better for their patients. If so, it may be time for all of us to shift our hope and energies toward the development of treatments whose effectiveness will be convincing to researchers and clinicians alike.
