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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.

Improving Functional Outcomes: Assessment and Management of Cognitive Dysfunction in Patients with Schizophrenia

To provide psychiatrists with up-to-date information on the assessment and management of cognitive dysfunction in patients with schizophrenia.
This activity is designed for psychiatrists. No prerequisites required.

The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, the participant should be able to:
  • Identify functional and neuroanatomical correlates of attention, executive function, and integrative processing of memory, emotion, and cognition.
  • Explain the role of cognitive function and potential therapeutic interventions in schizophrenia.
  • Describe a potential rationale for the use of therapeutic interventions that may affect cognition.
  • Review the latest clinical trials that will provide relevant data and information ontherapeutic strategies that will affect cognition.
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The estimated time to complete this educational activity: 2 hours.

Release date: March 15, 2007. Expiration date: March 15, 2009.

The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine name implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from Janssen, L.P. administered by Ortho-McNeil Janssen Scientific Affairs, LLC.Full Disclosure Policy Affecting CME Activities
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a sponsor has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Director and Participating Faculty reported the following:

Russell L. Margolis, MD
Professor of Psychiatry and Neurology
Director, Johns Hopkins Schizophrenia Program
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Margolis reports receiving grants/research support from Amarin Corporation plc and Forest Laboratories, Inc.

Nicola Cascella, MD
Assistant Professor
Department of Psychiatry
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Cascella reports receiving grants/research support from Acadia Pharmaceuticals and Astellas Pharma Inc; serving as a consultant for Gerson-Lehrman Group; and serving on the speakers' bureau for AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, and Pfizer, Inc.

Terry E. Goldberg, PhD
Division of Psychiatry Research
Zucker Hillside Hospital
Glen Oaks, New York
Dr Goldberg reports receiving royalties from the Brief Assessment of Cognition in Schizophrenia (assessment).

David J. Schretlen, PhD, ABPP
Associate Professor
Department of Psychiatry and Behavioral Sciences
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Schretlen reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Bruce E. Wexler, MD
Professor of Psychiatry
Yale University Department of Psychiatry
Connecticut Mental Health Center
New Haven, Connecticut
Dr Wexler reports serving as a consultant for Posit Science.
Notice: The audience is advised that an article in this CME activity contains reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Wexler–antidepressants and attention enhancing agents as drugs that might enhance the effects of the behavioral treatments, a possible future development.

All other faculty have indicated that they have not referenced unlabeled/unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty.  Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.Improving Functional Outcomes: Assessment and Management of Cognitive Dysfunction in Patients with Schizophrenia
Russell L. Margolis, MD*

Looking at the intensity of today's research efforts focusing on neuropsychology in schizophrenia, it is difficult to imagine a time when this disease was solely characterized by positive symptoms, such as hallucinations, delusions, and thought disorder. Cognitive impairment was once viewed as a mere artifact of patients' symptoms or treatment until a growing body of evidence eventually interlocked cognition with every aspect of schizophrenia. Although positive and negative symptoms still define the core of the Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases diagnostic constructs for schizophrenia, cognitive impairment is now recognized as a core feature of the disorder. Cognitive dysfunction is reliably present in the majority of patients throughout the course of the illness, is independent of positive symptoms, and is a major cause of poor social and vocational outcomes. Cognitive impairment directly affects patients' ability to live independently, obtain and maintain gainful employment, adhere to treatment, and perform basic daily functions. Just in the past several years, several studies have demonstrated that cognitive impairment in schizophrenia is widespread and lifelong, with particular problems noted in attention, declarative memory, and higher-order problem solving.

The treatment of schizophrenia has presented many challenges. Despite the fact that the majority of patients are partially or fully treatment responsive (ie, positive symptoms, such as delusions and hallucinations, are significantly reduced by antipsychotic medication), many of these responders are left with debilitating thought disorganization, motivational deficits, and disabilities in multiple cognitive domains. Whereas newer atypical antipsychotic agents may improve cognition, they clearly do not normalize it. As a result, there is a significant treatment gap that researchers from academia and industry hope to fill. If, in the meantime, patients are to be treated effectively, neuropsychological dysfunction specific to this disorder must be precisely defined and targeted for remediation therapy. Because of the heterogeneity of the disorder, different treatments may be effective in certain subgroups, and certain cognitive abilities may be more responsive to intervention and more relevant to clinical outcome than others.

In treating schizophrenia, psychiatrists must be attuned to the most current research relating to cognitive impairment and the impact of current pharmacologic and nonpharmacologic treatment strategies on cognitive function. This issue of Johns Hopkins Advanced Studies in Medicine is dedicated to educating psychiatrists on assessment and management of cognitive dysfunction in patients with schizophrenia. David J. Schretlen, PhD, ABPP, provides insight into the prevalence of cognitive impairment in schizophrenia, in addition to the nature and severity of the deficits and their functional significance. Dr Schretlen cites compelling studies suggesting that the vast majority of patients experience at least some degree of cognitive impairment, even those that appear cognitively intact. He discusses the challenges that researchers face in attempting to identify a neuropsychological profile of schizophrenia and offers a review of the literature evaluating various cognitive domains. Dr Schretlen also addresses the development process for a standardized cognitive battery, designed to serve as an outcome measure for clinical trials of cognition-enhancing drugs and cognitive rehabilitation programs.

Bruce E. Wexler, MD, offers an extensive discussion on the available nonpharmacologic strategies for treating cognitive dysfunctions, including cognitive remediation treatment (CRT) and compensatory therapy. Whereas CRT aims to enhance or restore compromised cognitive function through cognitive exercises that activate under-functioning neurocognitive systems, compensatory therapy offers patients strategies and tools to compensate for cognitive dysfunctions. In regard to CRT, Dr Wexler reviews basic science and principles, current selection of exercises, and demonstrated benefit and durability from the latest clinical trials. His coverage of compensatory treatment includes the types of adaptive skills used and the impact of social skills and vocational treatments. Dr Wexler also provides an update on new approaches involving various combinations of therapy and early intervention in the prodrome period of schizophrenia.

Terry E. Goldberg, PhD, presents an in-depth analysis of cognition trials involving first- and second-generation antipsychotics and discusses current strategies for improving research protocols for investigational agents that target cognitive function. In noting that atypical antipsychotics only modestly improve the considerable cognitive deficits seen in patients with schizophrenia, Dr Goldberg emphasizes the unmet treatment need in this area. He also highlights the accomplishments of the Institute of Mental Health-sponsored program, Measurement and Treatment Research to Improve Cognition in Schizophrenia, in regard to overcoming research barriers, devising a cognitive battery for use in clinical trials, and reaching a consensus on clinical trial design.

In contributing a case study on a Caucasian male with a history of chronic schizophrenia, Nicola Cascella, MD, offers insight into the use of adjunctive treatment to improve cognition. Because at this time there is no US Food and Drug Administration-approved cognitive-enhancing drug, clinicians must rely on agents, such as guanfacine, which are used for other indications but have limited cognition data.

Dr Cascella offers a detailed description of this agent's effect on one patient's cognitive function.
There is much to accomplish in the treatment of this daunting disorder. With this in mind, we have included a quick reference tear-out tool, which provides a synopsis of the important information provided in this monograph for use in your daily practice. By being more mindful of the cognitive impact of schizophrenia, psychiatrists can focus on this aspect of the illness and potentially improve patients' function in society and their quality of life.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his article and all its contents.

*Professor of Psychiatry and Neurology; Director, Johns Hopkins Schizophrenia Program, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Address correspondence to: Russell L. Margolis, MD, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 8-121, Baltimore, MD 21287.

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