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


A New Millennium In The Antipsychotic Treatment Of Patients With Bipolar Disorder


GOAL
The provide psychiatrists with information on the antipsychotic treatment of
bipolar disorder.

TARGET AUDIENCE
This activity is designed for psychiatrists. No prerequisites required.

LEARNING OBJECTIVES
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,
participants should be able to:

  • Discuss how bipolar disorder and borderline personality disorder may overlap
    in patients.
  • Identify goals of acute and maintenance treatment, choosing and switching agents, and obtaining the ideal balance of efficacy and tolerability in the treatment of bipolar disorder.
  • Evaluate the risks of using antipsychotic medications in the pediatric population.
  • Discuss the risks of altered prolactin production, weight gain, diabetes, and hyperlipidemia in antipsychotic drug therapy.

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. The estimated time to complete this educational activity: 2 hours.

Release date: December 15, 2004. Expiration date: December 15, 2006.

DISCLAIMER STATEMENT
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 Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc.

Full Disclosure Policy Affecting CME Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of 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 Directors and Participating Faculty reported the following:

PROGRAM DIRECTORS

Jennifer L. Payne, MD
Assistant Professor
Department of Psychiatry and Behavioral Sciences
Johns Hopkins UniversitySchool of Medicine
Baltimore, Maryland
Dr Payne reports receiving grants/research support from the National Alliance for Research on Schizophrenia and Depression and Stanley Medical Research Institute.

Rajiv Tandon, MD
Chief of Psychiatry
Florida Department of Children and Families
Tallahassee, Florida
Dr Tandon reports serving as a consultant to AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceutica, and Pfizer Inc.

PARTICIPATING FACULTY

Peter F. Buckley, MD
Professor and Chairman
Department of Psychiatry and Health Behavior
Medical College of Georgia
Augusta, Georgia
Dr Buckley reports receiving grants/research support from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceutica, Novartis Pharmaceuticals USA, Pfizer Inc, and Solvay SA; serving as a consultant to and receiving honoraria from Abbott Laboratories, Alamo Pharmaceuticals, AstraZeneca LP, Bristol-Myers  Squibb Company, Eli Lilly and Company, Janssen Pharmaceutica, Novartis Pharmaceuticals USA, Pfizer Inc, and Pharmstar Ltd; and serving on the speakers' bureaus for Abbott Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceutica, Novartis Pharmaceuticals USA, and Pfizer Inc.

Robert L. Findling, MD
Professor
Departments of Psychiatry and Pediatrics
University Hospitals of Cleveland/Case Western Reserve University
Cleveland, Ohio
Dr Findling reports receiving grants/research support from Abbott Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Celltech Group, Eli Lilly and Company, Forest Laboratories, Inc, GlaxoSmithKline, Johnson & Johnson, Novartis Pharmaceuticals USA, Otsuka America Pharmaceutical, Inc, Pfizer Inc, Shire Pharmaceuticals Group, Solvay SA, and Wyeth; serving as a consultant to Abbott Laboratories, AstraZeneca LP, Best Practices, Bristol-Myers Squibb Company, Celltech Group, Eli Lilly and Company, Forest Laboratories, Inc, GlaxoSmithKline, Johnson & Johnson, New River Pharmaceuticals Inc, Novartis Pharmaceuticals USA, Noven Pharmaceuticals, Otsuka America Pharmaceutical, Inc, Pharmaceutical Product Development, Inc, Pfizer Inc, Shire Pharmaceuticals Group, and Wyeth; and serving on the speakerÕs bureaus for Abbott Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Otsuka America Pharmaceutical, Inc, Shire Pharmaceuticals Group, and Wyeth.

Jeffrey Lieberman, MD
Vice Chair of Psychiatry
Department of Psychiatry
University of North CarolinaSchool of Medicine
Chapel Hill, North Carolina
Dr Lieberman reports receiving grants/research support from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutica, Novartis Pharmaceuticals USA, Organon, Pfizer Inc, and Sanofi-Synthelabo Inc; serving as a consultant to AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson, Novartis Pharmaceuticals USA, Pfizer Inc, and Solvay SA; and serving on the advisory boards for AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Organon, Pfizer Inc, and Solvay SA.

Diana O. Perkins, MD, MPH
Professor
Department of Psychiatry
University of North Carolina School of Medicine
Chapel Hill, North Carolina
Dr Perkins reports receiving grants/research support from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Otsuka America Pharmaceutical, Inc, and Pfizer Inc; and serving as a consultant to Bristol-Myers Squibb Company.

Notice: In accordance with the ACCME Standards for Commercial Support, the audience is advised that one or more articles in this continuing medical education activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices. The following faculty members have disclosed that their articles have referenced the following unlabeled/unapproved uses of drugs or devices:

Dr Buckley—carbamazepine, clozapine, divalproex, gabapentin, oxcarbazepine, tiagabin, topiramate, zonisamide.
Dr Findling—arbamazepine, clozapine, divalproex, lamotrigine.
Dr Lieberman—clozapine, divalproex, fluoxetine, fluvoxamine, risperidone.

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

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. 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.

A New Millennium In The Antipsychotic Treatment Of Patients With Bipolar Disorder
Jennifer L. Payne, MD,* and Rajiv Tandon, MD 

The advent of atypical antipsychotic agents has significantly increased our options for the treatment of schizophrenia and other mental disorders. These agents were developed to minimize the debilitating motor adverse effects of conventional agents while maintaining a high degree of efficacy. Indeed, the new agents have shown reduced propensity to cause extrapyramidal symptoms, and they provide additional benefits by ameliorating the negative and cognitive symptoms of schizophrenia along with the positive symptoms. Atypical antipsychotics, however, are associated with a variety of agent-specific adverse effects that must be taken into account before they are prescribed. Readers will note that a common thread running through all the articles in this issue is that, in contrast to the essentially similar efficacy among atypical agents, not all atypical antipsychotics have a very different adverse effect profile.

In this issue of Advanced Studies in Medicine, we examine the increasing role of atypical antipsychotics in the treatment of mental disorders other than schizophrenia, for which they were first developed. The first article, by Dr Jeffrey Lieberman, gives us a detailed account of borderline personality disorder, including a description of how its definition has evolved since 1938 when the term was coined by Stern to describe patients showing signs of both neurosis and psychosis. Since up to 29% of patients with bipolar disorder also meet criteria for borderline personality disorder, this is an important issue in the management of bipolar disorder. Dr Lieberman also reviews the epidemiology and the possible neuropathologic causes of borderline personality disorder and the strategies to treat it.

Bipolar disorder is a complex disease, and treating it is a major challenge. Dr Peter F. Buckley advocates focusing the goals of bipolar disorder treatment toward the critical outcomes of preventing suicide, maintaining symptomatic relief, and minimizing adverse effects. Lithium and the anticonvulsants divalproex sodium and carbamazepine, traditionally viewed as mood stabilizers, remain the cornerstones of treatment; however, atypical antipsychotics are being increasingly used. Dr Buckley outlines the strengths and limitations of lithium and the anticonvulsants, and he reviews the evidence for the efficacy of atypicals as monotherapy in the treatment of acute mania. Preliminary studies indicate that some agents may also show efficacy for maintenance therapy. This is encouraging news, and results from upcoming trials should provide us with more definitive answers.

A number of important issues add further complexity to the treatment of bipolar disorder in the pediatric population. In his article, Dr Robert L. Findling provides an overview of these issues, which include diagnostic problems, subtle differences between adults and children in neurotransmitter systems and disease course, greater vulnerability of children to a variety of adverse effects, and poor compliance. The atypical antipsychotics have shown promise in the treatment of bipolar disorder in children, but, as Dr Findling explains, the adverse effects are of particular concern.

The differential adverse effect profile of the atypicals is also the basis of the final article. Perhaps the least recognized adverse effect of the atypicals is hyperprolactinemia. Dr Diana O. Perkins discusses why this important adverse effect tends to be neglected. She also explains how antipsychotics cause elevations in plasma prolactin levels and details the consequences of this elevation. Dr Perkins discusses variations among different agents in the extent to which they cause hyperprolactinemia. For example, typical antipsychotics and risperidone cause the greatest elevations, whereas aripiprazole may cause a slight decline in plasma prolactin level.

In the next few pages, readers will be able to gain considerable insight into the issues surrounding the use of atypical antipsychotics in the treatment of bipolar disorder. Atypicals have provided us with a greater choice of agents so that the challenge now is to decide which agent to use for a given patient. In contrast to the essentially similar efficacy of atypical agents across various disorders, atypical antipsychotics have very different adverse effect profiles. The medical history of the patient and the adverse effect profiles of the agents should therefore factor into the decision-making process when initiating or switching treatment.

*Assistant Professor, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Chief of Psychiatry, Florida Department of Children and Families, Tallahassee, Florida.
Address correspondence to: Jennifer L. Payne, MD, Johns Hopkins University School of Medicine, Meyer 3-181, 600 North Wolfe St, Baltimore, MD 21287. E-mail:
jpayne5@jhmi.edu.





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