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

New Evidence-Based Approaches In Bipolar Disorder And Schizophrenia

To update the practicing psychiatrist on the diagnostic complexity and current treatment advances in bipolar disorder.

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, participants should be able to:

  • Recognize proper diagnostic techniques in bipolar disorder.
  • Demonstrate the salient issues in medication selection and assess the impact of medications on patients with schizophrenia or bipolar disorder with a high risk of medical comorbidities or metabolic complications.
  • Evaluate ways to optimize pharmacologic interventions and translate switching strategies into improved patient functioning.
  • Critique the latest research on mania and mixed episodes in patients with and without psychotic features.

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 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.

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 Pfizer 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 Director and Participating Faculty reported the following:


Glenn Treisman, MD
Associate Professor
Department of Psychiatry and Behavioral Sciences
The Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Treisman reports having no financial or advisory relationships with corporate organizations related to this activity.


Henry A. Nasrallah, MD
Associate Dean
Professor of Psychiatry, Neurology, & Neuroscience
University of Cincinnati Medical Center
Cincinnati, Ohio
Dr Nasrallah reports receiving grant and/or research support from AstraZeneca LP, Forest Laboratories, Janssen Pharmaceutica, and Pfizer Inc; serving as a consultant to Abbott Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Janssen Pharmaceutica, and Pfizer Inc; and receiving honoraria from Abbot Laboratories, AstraZeneca LP, Bristol-Myers Squibb Company, Janssen Pharmaceutica, and Pfizer Inc.

John W. Newcomer, MD
Associate Professor
Department of Psychiatry
Washington University School of Medicine
St Louis, Missouri
Dr Newcomer reports receiving grant and/or research support from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceutica, and Pfizer Inc; serving as a consultant for AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutica, and Pfizer Inc; and receiving honoraria from AstraZeneca LP, Bristol-Myers Squibb Company, Janssen Pharmaceutica, Pfizer Inc, and Sanofi-Synthelabo.

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.

All 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.

Expanding Our Understanding Of Antipsychotics And Associated Metabolic Issues
Glenn Treisman, MD*

With the advent of antipsychotic medications, psychiatry was able to make significant strides in managing serious psychiatric disorders and improving the quality of life for mentally ill individuals. More than half a century ago, Delay et al discovered that the antihistamine-like compound chlorpromazine could relieve psychotic symptoms.1 This came at a price because along with efficacy came iatrogenic parkinsonism—the first noted extrapyramidal side effect. Sedation, akathisia (motor restlessness), dystonia, and slowed motor movement were accompanied by a sense of being dulled and unreactive, which some patients describe as "zombie-like." These effects lead to decreased acceptance of the drugs by patients. A recent study showed that patients on the newer antipsychotic agents described below are more likely to get refilled prescriptions and continue treatment than with the traditional agents. The study also showed that minority patients are more likely to get the older "typical" agents.

Clozapine was the first atypical antipsychotic available for clinical use and, although there were drawbacks in its use (risk of neutropenia or agranulocytosis), it was more effective than conventional antipsychotics for patients with schizophrenia who were severely psychotic and poorly responsive to the mechanism of action of conventional antipsychotic drugs. This set the stage to demonstrate that the atypical antipsychotics were significantly more effective on a broad range of psychopathology that included positive and negative symptoms. In fact, some individuals who were considered treatment refractory showed improvement that led to substantial gains in social and occupational adjustment.

Five new atypical antipsychotic medications have been introduced in the United States in the past decade: olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole. These newer agents have a lower tendency than the older medications to cause extrapyramidal side effects and a lower risk of causing tardive dyskinesia. More recently, it has been shown that the newer agents favorably affect cognitive dysfunction2 and other symptoms that may be important in improving a patient's level of functioning and compliance with the medications. Another recent development is the approval of these agents by the US Food and Drug Administration (FDA) for treatment of bipolar mania, in addition to schizophrenia.

Differences in Side Effects
Although the second-generation antipsychotics have a low propensity for causing extrapyramidal side effects, there are differences among the various drugs. Some drugs are still more likely than others to cause motor difficulties, such as dystonia and tardive dyskinesia. Other drugs may have an increased liability for prolonging QTc interval. Some drugs have been noted to cause weight gain and insulin resistance. Endocrine and metabolic side effects have received increased attention within the past few years. These side effects include weight gain,3 diabetes,4 and hyperprolactinemia.5 It is becoming clear that patients with schizophrenia represent a group that is especially vulnerable to comorbid medical conditions, and recent data suggest that this also may be true of bipolar disorder.6

Weight gain is more likely with some of the atypical medications and much less likely with others. The report from the Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes7 contains valuable advice for the monitoring of patients who are at risk for type 2 diabetes. The report also notes the importance of monitoring serum lipid levels; available evidence suggests that changes in serum lipids are consistent with changes in body weight.7 The FDA has instructed the manufacturers of all second-generation antipsychotics to include a warning on their product label about the possible effects of these drugs on hyperglycemia and diabetes.

In this issue of Advanced Studies in Medicine, we review in detail the important issues to consider when prescribing atypical antipsychotics, especially when it pertains to the metabolic impact on the patients that we treat. This review is practical and geared toward the practicing clinician.

An interview with John W. Newcomer, MD, offers a valuable and unique perspective on our understanding of the metabolic issues affecting individuals with serious mental illness. He reviews the concepts of primary and secondary prevention and offers hope for the treating clinicians and patients alike when he discusses modifiable risk factors.

Dr Newcomer and Henry A. Nasrallah, MD, each present a case study that helps delineate some of the complexities involved in treating patients with atypical antipsychotics. In addition, an article by them outlines the state of our knowledge on metabolic issues in prescribing antipsychotic medications.

1. Delay J, Deniker P, Harl JM. Therapeutic use in psychiatry of phenothiazine of central elective action (4560 RP). Ann Med Psychol (Paris). 1952;110:112-117.
2. Harvey PD. Ziprasidone and cognition: the evolving story.
J Clin Psychiatry. 2003;64(suppl 19):33-39.
3. McIntyre RS, Trakas K, Lin D, et al. Risk of weight gain associated with antipsychotic treatment: results from the Canadian National Outcomes Measurement Study in Schizophrenia. Can J Psychiatry. 2003;48:689-694.
4. Citrome L. The increase in risk of diabetes mellitus from exposure to second generation antipsychotics. Drugs Today. 2004;40:445-464.
5. Volavka J, Czobor P, Cooper TB, et al. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol.
J Clin Psychiatry. 2004;65:57-61.
6. Masand PS, Fazal FS, Patkar AA. Safety considerations in pharmacotherapy of bipolar disorder. CNS Spectr. 2004;9(suppl 12):16-26.
7. American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596-601.

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

Address correspondence to: Glenn Treisman, MD, Associate Professor, Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 4-119, Baltimore, MD 21205. E-mail:

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