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CME

Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizophrenia: Efficacy and Safety Outcomes of the CATIE Trial

  • Authors: Jeffrey A. Lieberman, MD; Joseph P. McEvoy, MD; Diana O. Perkins, MD, MPH; Susan M. Essock, PhD; John W. Newcomer, MD; Peter J. Weiden, MD
  • THIS ACTIVITY HAS EXPIRED
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Target Audience and Goal Statement

This activity has been planned in accordance with the need to provide clinical psychiatrists with information on the impact of clinical effectiveness studies, such as CATIE, on therapeutic choices in the management of patients with schizophrenia.

The goal of this activity is for clinicians to apply scientific research from the CATIE study into their clinical practice.

Upon completion of this activity, participants should be able to:

  1. Differentiate among the antipsychotics included in the CATIE study within the parameters of safety, efficacy, and tolerability.
  2. Assist clinicians in drawing clinically relevant conclusions for the treatment of patients with schizophrenia.


Disclosures

It is the policy of The Center for Health Care Education, LLC, that faculty disclose to the attendees (1) when products/devices or procedures being discussed are off-label, unlabeled, experimental, and/or investigational (not FDA approved); and (2) any limitations on the information that is presented, such as data that are preliminary or that represent ongoing research, interim analyses, and/or unsupported opinion. Clinicians have the professional responsibility to ensure that drugs are prescribed and used appropriately on the basis of their own clinical judgment and accepted standards of care. Please consult approved labeling for full prescribing information.

It is the policy of The Center for Health Care Education, LLC to ensure balance, independence, objectivity, and scientific rigor in all its sponsored educational activities. All faculty participating in a sponsored activity are expected to disclose to the participants any significant financial interest or other relationship with manufacturer(s) of any commercial product(s)/device(s) and/or provider(s) of commercial services included in the educational activity. The intent of this disclosure is not to prevent a faculty member with a relevant financial or other relationship from participating in the activity, but rather to provide participants with information on which they can make their own judgments. The CHCE has identified and resolved all faculty conflicts of interest prior to the release of this activity.


Author(s)

  • Susan M. Essock, PhD

    Professor, Mt. Sinai School of Medicine, Department of Psychiatry, New York, NY

    Disclosures

    Disclosure: Dr. Essock has no financial relationships to disclose.

  • Jeffrey A. Lieberman, MD

    Lawrence E. Kolb Chairman of Psychiatry, Columbia University College of Physicians and Surgeons, Department of Psychiatry, Director, New York State Psychiatric Institution, New York, NY

    Disclosures

    Disclosure: Grant Support: Acadia, Bristol-Myers Squibb, GlaxoSmithKline; Patent: Repligen.

  • Joseph P. McEvoy, MD

    Associate Professor, Department of Psychiatry & Behavioral Science, Duke University, Durham, NC

    Disclosures

    Disclosure: Grants Support: AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutica, Eli Lilly & Company, Pfizer Inc; Consultant: Bristol-Myers Squibb, Pfizer Inc; Honoraria: Janssen Pharmaceutica, Bristol-Myers Squibb.

  • John W. Newcomer, MD

    Associate Professor, Department of Psychiatry & Behavioral Science, Duke University, Durham, NC

    Disclosures

    Disclosure: Grants Support: AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutica, Eli Lilly & Company, Pfizer Inc; Consultant: Bristol-Myers Squibb, Pfizer Inc; Honoraria: Janssen Pharmaceutica, Bristol-Myers Squibb.

  • Diana O. Perkins, MD, MPH

    Professor, Department of Psychiatry, University of North Carolina, Chapel Hill, NC

    Disclosures

    Disclosure: Grant Support: Eli Lilly & Company, Pfizer Inc, Bristol-Myers Squibb, Otsuka, AstraZeneca; Consultant: Bristol-Myers Squibb, Shire; Honoraria: Bristol-Myers Squibb, Eli Lilly &; Company, Pfizer Inc.

  • Peter J. Weiden, MD

    Director of the Psychosis Program, Center for Cognitive Medicine, Department of Psychiatry, University of Illinois Medical Center, Chicago, Illinois

    Disclosures

    Disclosure: Grant Support: AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutica, Pfizer Inc; Consultant: AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutica, Organon, Pfizer Inc, VANDA; Honoraria: AstraZeneca, Bristol-Myers Squibb, Janssen Pharmaceutica, Pfizer Inc.


Accreditation Statements

    For Physicians

  • This activity is sponsored by The Center for Health Care Education, Inc (CHCE).

    This activity has been planned and produced in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). The Center for Health Care Education, Inc, is accredited by the ACCME to provide continuing medical education for physicians.

    The Center for Health Care Education, LLC, designates this educational activity for a maximum of 2.0 AMA PRA Category 1 Credit(s) TM . Physicians should only claim credit commensurate with the extent of their participation in the activity.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

Follow these steps to earn CME/CE credit*:

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You may now view or print the certificate from your CME/CE Tracker. You may print the certificate but you cannot alter it. Credits will be tallied in your CME/CE Tracker and archived for 6 years; at any point within this time period you can print out the tally as well as the certificates by accessing "Edit Your Profile" at the top of your Medscape homepage.

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CME

Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizophrenia: Efficacy and Safety Outcomes of the CATIE Trial

Authors: Jeffrey A. Lieberman, MD; Joseph P. McEvoy, MD; Diana O. Perkins, MD, MPH; Susan M. Essock, PhD; John W. Newcomer, MD; Peter J. Weiden, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

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Introduction, Presented by Jeffrey A. Lieberman, MD

Atypical Antipsychotics

  •  
  • Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizoph

    Slide 1.

    Effectiveness of Antipsychotic Drugs in Patients With Chronic Schizophrenia: Efficacy and Safety Outcomes of the CATIE Trial: Introduction

    (Enlarge Slide)
  • I think the story begins really in 1989 or 1990 when this issue of Time appeared and that was to symbolize or to reflect the introduction of clozapine, which was supposed to have been a new class of antipsychotic drugs, potentially a breakthrough -- the most significant innovation in antipsychotic pharmacology since the introduction of chlorpromazine. And like what happened when chlorpromazine was introduced, people thought that this really amazing thing and that the cure for mental illness might be at hand. The field quickly embraced this, as did the families, patients; and with the introduction of antipsychotic drugs, which were reputed to be clozapine-like, the new so-called atypical second-generation antipsychotic drugs got an increasing share of the market. Now, more than 9 out of every 10 prescriptions written for an antipsychotic drug is for one of the newer ones.

  • Slide

    Slide 2.

    (Enlarge Slide)
  • So the prevalence of use is very high, suggesting that there's a belief in their superiority for one reason or another. As a result of this preferential use, the cost of this class of drugs has gotten increasingly substantial to the point that now the US market is about $10 billion a year, the global market is $14 billion a year, and this, along with the cost of other drugs, has put a real strain on the budgets of Medicaid and other third party payers.

  • US Atypical Antipsychotic Market Is Large and Expanding

    Slide 3.

    US Atypical Antipsychotic Market Is Large and Expanding

    (Enlarge Slide)
  • The reasons why they became so popular were because they were believed to have increased efficacy, fewer side effects, better long-term outcome, and even though they would cost more, they would reduce health care services and increase productivity, and therefore, in the long run, be cost-effective. Those were the initial expectations and claims, but now we're over a decade into the second-generation antipsychotic drug era, and the efficacy claims are really not robustly or consistently substantiated.

  • Implications of Atypical Antipsychotic Therapy for the Future

    Slide 4.

    Implications of Atypical Antipsychotic Therapy for the Future

    (Enlarge Slide)
  • The side effect issue has become more complicated, as we're going to hear, and I'll say more about it in a second, and the improvement in long-term outcome really hasn't been demonstrated; as for cost-effectiveness, the data just plain ain't there.

    The side effect issue is more complicated, because the first-generation drugs were mainly limited by the high rates of neurologic side effects -- acute extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) The newer medicines definitely have a lower or negligible incidence of EPS or TD, but they by varying degrees have an increased propensity relative to the first-generation drugs to cause weight gain or metabolic side effects, influencing glucose and lipid metabolism. This has raised concerns and questions as to whether we simply traded neurologic for metabolic side effects with the newer medicines.

  • Side Effects of Atypical Antipsychotics: Shift in Risk Perception

    Slide 5.

    Side Effects of Atypical Antipsychotics: Shift in Risk Perception

    (Enlarge Slide)

A Need for Practical Clinical Trials of Atypical Antipsychotics

  • Now in order to try and get a more objective and definitive answer as to whether the new-generation medicines have been an advance and whether they're worth the incremental cost, one would want to look at the studies in the literature, but there are real limitations to these. The majority of studies published in the scientific literature derive from short-term studies that were designed for regulatory approval or labeling language; the comparators are either placebo or a single active agent, the results have limited generalizability because they don't always have representative patient samples and are not done in representative clinical settings or under so-called real-world treatment conditions. The vast majority of such studies are sponsored by pharma, and that's an essential source of sponsorship but the motivations and goals of a pharmaceutical company are different from academic and public mental organizations. In addition, there is the question of bias and preferred outcome,raising questions about the credibility of the studies. In the absence of empirical data, clinicians have relied on their own experience with the medications or case reports, but clinical experience, the case reports are an inadequate substitute for real data from clinical trials.

  • Limitations of Our Knowledge

    Slide 6.

    Limitations of Our Knowledge

    (Enlarge Slide)
  • Consequently, there's been a stronger call for practical clinical trials; these are studies designed to answer questions faced by clinicians and policy makers to compare clinically relevant alternative interventions, collect data on a broad range of health outcomes that are meaningful, include representative patients, and carry out the trials in representative settings that reflect "real-world" treatment conditions.

  • Call for Practical Clinical Trials

    Slide 7.

    Call for Practical Clinical Trials

    (Enlarge Slide)
  • The National Institute of Mental Health (NIMH) has pursued the sponsorship of practical clinical trials, initially with the Treatment for Adolescent Depression Study (TADS), and subsequently with the STEP bipolar disorder study and the STAR depression study, and the CATIE study -- these are all acronyms, of course, for much longer titles -- the CATIE study is the one that evaluates the effectiveness of antipsychotic drugs in the conditions for which they're used; first and foremost is schizophrenia, but they also could include Alzheimer's disease with psychosis and agitation and psychotic depression, bipolar disorder.

  • NIMH-Sponsored Practical Clinical Trials

    Slide 8.

    NIMH-Sponsored Practical Clinical Trials

    (Enlarge Slide)

CATIE Schizophrenia Trial: Overview

  • The CATIE schizophrenia trial asked 3 simple questions: How do the second-generation drugs compare to a representative first-generation antipsychotic drug? What is the comparative effectiveness of the second-generation antipsychotic drugs? And are the second-generation drugs cost-effective?

  • Primary Questions Addressed by CATIE Schizophrenia Trial

    Slide 9.

    Primary Questions Addressed by CATIE Schizophrenia Trial

    (Enlarge Slide)
  • This study was sponsored by the NIMH; it was coordinated by a group of universities that received the contract for this award. The study was managed by a contract research organization that was retained and implemented at a network of sites -- 57 sites in 24 states around the United States that were reflective of the different systems of care where people with schizophrenia generally received treatment, including HMOs, private group practice sites, VA hospitals, state mental health clinics or hospitals, academic medical centers.

  • CATIE: Clinical Antipsychotic Trials of Intervention Effectiveness

    Slide 10.

    CATIE: Clinical Antipsychotic Trials of Intervention Effectiveness

    (Enlarge Slide)
  • The study involved 1460 patients with analyzable data who were followed for up to 18 months.

  • CATIE Schizophrenia Trial: Overview

    Slide 11.

    CATIE Schizophrenia Trial: Overview

    (Enlarge Slide)
  • Inclusion criteria were broad and minimal; basically, you had to have schizophrenia and not be in a first episode or treatment resistant, ie, with a history of symptoms not responding to prior treatment. You could have psychiatric or medical comorbidities; you could take any other medicines that you wanted. The only thing was that after you were assigned to your study antipsychotic, you couldn't continue to take an antipsychotic except for the purposes of cross titration. We allowed cross titration for up to a month to allow people to be stably assigned or transition from their prior medication to their assigned antipsychotic drug.

  • CATIE: Broad Inclusion and Minimal Exclusion Criteria

    Slide 12.

    CATIE: Broad Inclusion and Minimal Exclusion Criteria

    (Enlarge Slide)
  • The design of the study appears complicated. It's a 5-arm, randomized controlled trial lasting 18 months, recognizing the fact that not everyone who would be assigned to an antipsychotic medication was going do well enough to warrant them staying on it for 18 months. The design provided for changing treatment in a second and third phase. This allowed for re-randomization or switching to another medication in a way that tried to approximate what happens in clinical -- real clinical care and treatment selection decision-making. And basically, after people were assigned to their initial medication, if the treatment didn't work for reasons that we'll talk about in a minute, they could be re-randomized in phase 2, and if that didn't work they could then choose among 8 different treatments that were geared to reflect all the treatment options that are available to somebody who has had some unsuccessful treatment, albeit for efficacy or safety reasons.

  • CATIE Schizophrenia Trial Design

    Slide 13.

    CATIE Schizophrenia Trial Design

    (Enlarge Slide)