Clinical Issues in Bipolar Depression

CATHERINE

Judd, MS, PA-C, CAQ-Psy, DFAAPA

ROGER S.

McIntyre, MD, FRCPC Jointly provided by North American Center for Continuing Medical Education, LLC, an HMP Communications Holdings Company, and Integritas Communications This activity is supported by an educational grant from Sunovion Pharmaceuticals Inc.

GARY S.

Sachs, MD

CME/MEDICAL COMMUNICATIONS INQUIRIES info@integritasgrp.com integritasgrp.com

FACULTY FACULTY

CATHERINE Judd, MS, PA-C, CAQ-Psy, DFAAPA Clinical Assistant Professor UT Southwestern Medical Center Senior Physician Assistant, Mental Health Services Parkland Health and Hospital System Dallas, Texas Catherine Judd is a Senior Physician Assistant (PA) at Parkland Health and Hospital System, Jail Mental Health Program, Dallas, Texas, and Clinical Instructor and Psychiatry Preceptor at the University of Texas (UT) Dallas PA Program. She has served as a representative from AAPA on the Accreditation Review Commission for PA Programs, and on the National Commission Certification of Physician Assistants (NCCPA) Certificate of Added Qualifications (CAQ) Advisory Committee.

Her clinical practice over the past 30 years has primarily encompassed adult and geriatric mental health. She has worked internationally in Egypt, for the Peace Corps in Uzbekistan, and for a private aid organization in Ghana. She has special interests in patients with serious mental illness and in geriatric patients with mood disorders and cognitive decline. Research interests have included cognitive behavioral therapy in depression in the Psychosocial Research Center and in the Psychoneuroendocrinology Research Group at UT Southwestern Department of Psychiatry, Dallas, where she held a faculty associate position.

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FACULTY

ROGER S. McIntyre, MD, FRCPC Professor of Psychiatry and Pharmacology University of Toronto Executive Director, Brain and Cognition Discovery Foundation (BCDF) Head, Mood Disorders Psychopharmacology Unit University Health Network Toronto, Ontario, Canada Dr. Roger McIntyre is a Professor of Psychiatry and Pharmacology at the University of Toronto and Head of the Mood Disorders Psychopharmacology Unit at the University Health Network, Toronto, Canada. Dr. McIntyre is also Executive Director of the Brain and Cognition Discovery Foundation in Toronto, Canada.

In 2014, Dr. McIntyre was named by Thomson Reuters as one of “The World’s Most Influential Scientific Minds.” This distinction is earned by having published the largest number of articles that rank among those most frequently cited by researchers globally in 21 broad fields of science and social science during the previous decade.

Dr. McIntyre is involved in multiple research endeavors that primarily aim to characterize the association between mood disorders, notably cognitive function and medical comorbidity. His work broadly aims to characterize the underlying causes of cognitive impairment in individuals with mood disorders and their impact on workplace functioning. This body of work has provided a platform for identifying novel molecular targets to treat and prevent mood disorders and accompanying cognitive impairment.

Extensively involved in medical education, Dr. McIntyre is a highly sought-after speaker at both national and international meetings. He has received several teaching awards from the University of Toronto, Department of Psychiatry, and has received the joint Canadian Psychiatric Association (CPA) / Council of Psychiatric Continuing Education Award for the Most Outstanding Continuing Education Activity in Psychiatry in Canada.

Dr. McIntyre participates in the Canadian Network for Mood and Anxiety Treatments (CANMAT) as cochair of the Task Force on the Treatment of Comorbidity in Adults with Major Depressive Disorder or Bipolar Disorder, as a contributor to the CANMAT guidelines for the management of depressive

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FACULTY

disorders and bipolar disorders, and as chair of Business and Research Development. He has published hundreds of peer-reviewed articles and has edited or coedited several textbooks on mood disorders.

Dr. McIntyre completed his medical degree at Dalhousie University, Halifax, Nova Scotia, Canada. He received his psychiatry residency training and Fellowship in Psychiatric Pharmacology at the University of Toronto.

GARY S. Sachs, MD Associate Clinical Professor of Psychiatry Harvard Medical School Founding Director, Bipolar Clinic and Research Program Massachusetts General Hospital Boston, Massachusetts Dr. Gary Sachs is Associate Clinical Professor in Psychiatry at Harvard Medical School and a Psychiatrist at the Massachusetts General Hospital (MGH).

The Founding Director of the MGH Bipolar Clinic and Research Program and founder of the Collaborative Care Initiative, he is also Clinical Vice President and Therapeutic Area Leader in bipolar disease and mood disorders at Bracket.

Dr. Sachs led the largest treatment study ever conducted for bipolar disorder as Principal Investigator of the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

As a recipient of a National Institutes of Health Small Business Innovation Research Grant, he founded Concordant Rater Systems and holds patents for methods to improve endpoint reliability in clinical trials. He currently focuses his work on clinical trial methodology, innovative approaches to clinical practice, and patient-centered research.

A corporate Board member of the Depression and Bipolar Support Alliance (DBSA), Dr. Sachs cochairs the DBSA’s scientific advisory board. He served on the executive committee of the International Society for CNS Clinical Trial Methodology and chaired the Scientific Advisory Board for the National Alliance on Mental Illness. He also served as Co-editor-in-chief of the Clinical Approaches to Bipolar Disorder and on the editorial boards of Current Psychiatry, Medscape, and the Psychotic Disorders Review, among numerous others. He has authored over 200 articles, abstracts, books, reviews, and book chapters.

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Dr. Sachs has received many awards, including the Thouron Scholarship, Laughlin Fellowship, Dunlop Award for psychiatric research and writing, Dupont-Warren Fellowship at the Harvard Medical School, and Massachusetts Psychiatric Association’s Research Award. He is a distinguished fellow of the American Psychiatric Association and is recognized as a “Top Doctor” by U.S. News & World Report.

Dr. Sachs earned his medical degree at the University of Maryland School of Medicine. He interned in family practice and psychiatry at the University of Maryland Hospital in Baltimore and was a resident in psychiatry and Chief Resident in Acute Psychiatry Service at MGH.

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INTENDED LEARNERS This activity is designed for psychiatrists, primary care physicians, psychologists, nurse practitioners, physician assistants, psychiatric nurses, and other healthcare professionals involved in the management of patients with bipolar disease.

LEARNING OBJECTIVES • Accurately diagnose bipolar depression, including episodes that meet the criteria for the mixed features specifier in the DSM-5, based on comprehensive patient evaluations and collateral histories • Discuss the clinical profiles of and long-term management considerations for medications that are available to treat bipolar depression • Tailor therapeutic regimens for major depressive episodes experienced by patents with bipolar disorder or by those at increased risk for emergent hypomania/mania • Communicate with patients with bipolar depression to provide disease state education, encourage shared decision-making, and improve treatment adherence

ACCREDITATION INFORMATION In support of improving patient care, North American Center for Continuing Medical Education (NACCME) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.

CME NACCME designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

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After completing this activity, participants should be able to:

CNE This continuing nursing education activity awards 1.5 contact hours.

Provider approved by the California Board of Registered Nursing, Provider #13255 for 1.5 contact hours.

NURSING PSYCHOPHARMACOLOGY CREDITS This continuing educational activity awards up to 0.75 pharmacology hours.

PREAMBLE

APA North American Center for Continuing Medical Education, LLC (NACCME), is approved by the American Psychological Association to sponsor continuing education for psychologists. NACCME maintains responsibility for this program and its content.

Instructional Level: Advanced Independent Clinical Reviewer: Douglas L. Noordsy, MD, Clinical Professor of Psychiatry and Behavioral Sciences, Director of Sports Psychiatry, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California Nurse Planner: Andrew Penn, RN, MS, NP, CNS, APRN-BC, Psychiatric Nurse Practitioner, Kaiser Permanente, Redwood City, California; Assistant Clinical Professor, School of Nursing, University of California, San Francisco, California

PLANNING COMMITTEE The planning committee is composed of Catherine Judd, MS, PA-C, CAQ-Psy, DFAAPA, Roger S. McIntyre, MD, FRCPC, Gary S. Sachs, MD; Douglas L. Noordsy, MD, Andrew Penn, RN, MS, NP, CNS, APRN-BC; Jim Kappler, PhD, Rose O’Connor, PhD, Integritas Communications; Raquel Gaerlan, Mike Kearney, Meaghan O’Brien, Randy Robbin, and John Savage, NACCME.

FINANCIAL DISCLOSURE and CONFLICTS of INTEREST According to the disclosure policy of NACCME, faculty, editors, managers, and other individuals who are in a position to control content are required to disclose any relevant financial relationships with relevant commercial companies related to this activity. All relevant conflicts of interest that

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are identified are reviewed for potential conflicts of interest. If a conflict is identified, it is the responsibility of NACCME to initiate a mechanism to resolve the conflict(s). The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation.

All educational materials are reviewed for fair balance, scientific objectivity of studies reported, and levels of evidence.

Roger S. McIntyre, MD, FRCPC Advisory Board: AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, Inc., Janssen Pharmaceuticals, Inc., Johnson & Johnson, Lundbeck, Mitsubishi Tanabe Pharma Corporation, moksha8 Pharmaceuticals Inc., Otsuka Canada Pharmaceutical, Inc., Pfizer Inc., Purdue Pharma L.P., Shire Plc, Sunovion Pharmaceuticals Inc., Takeda Canada Inc. Speaker Fees: AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, Inc., Janssen Pharmaceuticals, Inc., Johnson & Johnson, Lundbeck, Mitsubishi Tanabe Pharma Corporation, moksha8 Pharmaceuticals Inc., Otsuka Canada Pharmaceutical, Inc., Pfizer Inc., Purdue Pharma L.P., Shire Plc, Sunovion Pharmaceuticals Inc., Takeda Canada Inc. Research Grants: Allergan plc, AstraZeneca, Janssen Pharmaceuticals, Inc., Lundbeck, Pfizer Inc., Purdue Pharma L.P., Otsuka Canada Pharmaceutical, Inc., Shire Plc Gary S. Sachs, MD Advisory Board: Allergan plc, Janssen Pharmaceuticals, Inc., Lundbeck, Otsuka America Pharmaceutical, Inc., Sunovion Pharmaceuticals Inc., Supernus Pharmaceuticals, Inc., Takeda Pharmaceuticals U.S.A., Inc. Dr. Noordsy and Mr. Penn disclosed no relevant financial relationships with any commercial interests.

Ms. Gaerlan, Mr. Kearney, Ms. O’Brien, Mr. Robbin, Mr. Savage, Dr. Kappler, and Dr. O’Connor disclosed no relevant financial relationships with any commercial interests.

NACCME requires faculty to inform participants whenever off-label/ unapproved uses of drugs and/or devices are discussed in their presentations.

Off-label/unapproved uses of drugs and/or devices will be disclosed prior to the start of the symposium.

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Catherine Judd, MS, PA-C, CAQ-Psy, DFAAPA Disclosed no relevant financial relationships with any commercial interests.

ADA STATEMENT North American Center for Continuing Medical Education complies with the legal requirements of the Americans with Disabilities Act and the rules and regulations thereof. If any participant in this educational activity is in need of accommodations, please call 609-371-1137.

There is no fee associated with this activity.

For questions regarding this educational activity, please call 609-371-1137.

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HARDWARE/SOFTWARE REQUIREMENTS The evaluation is accessible after the activity via a PC (Windows 2000/XP/ Vista/7) or Mac (Mac OS 10.x or later) computer with current versions of the following browsers: Internet Explorer, Mozilla Firefox, Google Chrome, or Safari. A PDF reader is required for print publications. Please direct technical questions to webmaster@naccme.com.

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Copyright Š 2016 by North American Center for Continuing Medical Education, LLC. All rights reserved. No part of this accredited continuing education activity may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from North American Center for Continuing Medical Education. The opinions expressed in this educational activity are those of the faculty and are not attributable to NACCME. Clinical judgment must guide each professional in weighing the benefits of treatment against the risk of toxicity. Dosages, indications, and methods of use for products referred to in this activity are not necessarily the same as indicated in the package insert for each product, may reflect the clinical experience of the presenters, and may be derived from the professional literature or other clinical sources. Consult complete prescribing information before administering.

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INSTRUCTIONS for PARTICIPANTS to COMPLETE SESSION EVALUATION and RECEIVE DOCUMENTATION of CREDIT To confirm participation and receive CME/CE credit, attendees are required to complete activity evaluations for each session attended. After you attend your sessions, please log on to ww5.aievolution.com/upm1601. You will need your badge ID, which is located on your 2016 Psych Congress badge. Your password is PSY2016. Session ID: FS1

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After logging in, follow the instructions on the screen to complete your evaluations. After the completion of all relevant session evaluations, attendees must complete a Psych Congress 2016 General Survey before credits can be claimed.

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GUIDELINES »» Diagnostic and Statistical Manual of Mental Disorders (Fifth edition). 2013.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (Fifth edition). Arlington, VA: American Psychiatric Publishing. http://www.dsm5.org/Pages/Default.aspx

»» The American Psychiatric Association Practice Guidelines for the Psychiatric Evaluation of Adults (Third edition). 2016.

Arlington, VA: American Psychiatric Publishing. http://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890426760

»» 2015 Florida Best Practice Psychotherapeutic Medication Guidelines for Adults.

The University of South Florida, Florida Medicaid Drug Therapy Management Program for Behavioral Health. http://www.medicaidmentalhealth.org/– assets/file/Guidelines/ Web-2015-Psychotherapeutic%20Medication%20Guidelines%20for%20 Adults – Final – Approved1.pdf

CLINICAL TOOLS »» Clinically Useful Depression Outcome Scale with questions for the DSM-5 mixed features specifier (CUDOS-M) This self-administered assessment scale detects the presence of mixed features in patients with major depressive disorder. In this rating scale of 0-4, where 0 is not at all true and 4 is almost always true, patients endorse the frequency of each symptom experienced during the prior week (Zimmerman M, et al. J Affect Disord.

2014;168:357-362).

RESOURCE CENTER

http://www.ncbi.nlm.nih.gov/pubmed/25103631

»» Montgomery-Asberg Depression Rating Scale (MADRS) This clinician-scored questionnaire assesses the severity of patient depression over the prior week on a scale of 0-6, where 0 denotes no symptoms and 6 indicates the most severe symptoms (Montgomery SA, Asberg M. Brit J Psychiatry. 1979;134:382-389). http://www.psy-world.com/madrs.htm

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»» The Bipolarity Index This clinician-rated scale aims to provide diagnostic confidence when evaluating a patient with suspected bipolar disorder. Five sections evaluating the 5 illness dimensions are each scored from 0-20, with a final score ≥50 indicative of bipolar disorder (Sachs GS. Acta Psychiatr Scand. 2004;422(suppl):S7-S17; Aiken CB, et al. J Affect Disord. 2015;177:59-64). http://www.moodtreatmentcenter.com/aikenweislerbipolarityindex.pdf

»» The Mood Disorder Questionnaire (MDQ) This self-administered assessment scale is intended to help clinicians screen patients for bipolar disorder. The 5-question evaluation can be completed in less than 5 minutes and provides important insight into diagnosis and treatment. A positive screen is noted if a patient answers YES to ≥7 out of 13 items in question 1, YES to question 2, and MODERATE or SERIOUS to question 3 (Hirschfeld RMA. Prim Care Companion J Clin Psychiatry. 2002;4(1):9-11). http://www.dbsalliance.org/pdfs/MDQ.pdf

»» Young Mania Rating Scale (YMRS) This clinician-guided assessment is intended to identify the severity of patient abnormalities. The 11-statement assessment is used to describe the patient’s symptoms over the prior week through scoring on a 0-4 scale, where 0 is absence of symptoms (feeling normal) and 4 indicates the most severe symptoms (Young RC, et al. Br J Psychiatry. 1978;133(5):429-435). http://www.psych.uic.edu/csp/images/stories/physicians/rating%20scales/ YMRS.pdf

PATIENT RESOURCE »» Depression and Bipolar Support Alliance The Depression and Bipolar Support Alliance (DBSA) offers resources for patients, materials for clinicians, information on mental health research, as well as listings of patient support groups across the United States.

SUGGESTED READING »» Major depressive disorder and bipolar disorder predispose youth to accelerated atherosclerosis and early cardiovascular disease: a scientific statement from the American Heart Association.

Goldstein BI, et al. Circulation. 2015;132(10):965-986. http://circ.ahajournals.org/content/132/10/965.long

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RESOURCE CENTER

http://www.dbsalliance.org/

»» Mixed specifier for bipolar mania and depression: highlights of DSM-5 changes and implications for diagnosis and treatment in primary care.

Hu J, et al. Prim Care Companion CNS Disord. 2014;16(2). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116292/

»» The prevalence and illness characteristics of DSM-5-defined “mixed feature specifier” in adults with major depressive disorder and bipolar disorder: Results from the International Mood Disorders Collaborative Project.

McIntyre RS, et al. J Affect Disord. 2015;172:259-264. http://www.ncbi.nlm.nih.gov/pubmed/25451425

»» Lurasidone in the treatment of bipolar depression with mixed (subsyndromal hypomanic) features: post hoc analysis of a randomized placebo-controlled trial.

McIntyre RS, et al. J Clin Psychiatry. 2015;76(4):398-405. http://www.psychiatrist.com/JCP/article/– layouts/ppp.psych.controls/BinaryViewer.ashx?Article=/jcp/ article/Pages/2015/v76n04/v76n0402.aspx&Type=Article

»» Mixed depression in bipolar disorder: prevalence rate and clinical correlates during naturalistic follow-up in the Stanley Bipolar Network.

Miller S, et al. Am J Psychiatry. 2016;173(10):1015-1023. https://www.ncbi.nlm.nih.gov/pubmed/27079133

»» A 6 week randomized double-blind placebo-controlled trial of ziprasidone for the acute depressive mixed state.

Patkar A, et al. PLoS One. 2012;7(4):e34757.

RESOURCE CENTER

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034757

»» Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Perlis RH, et al. Am J Psychiatry. 2006;163(2):217-224. http://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.163.2.217

»» Mixed features in patients with a major depressive episode: the BRIDGE-II-MIX study.

Perugi G, et al. J Clin Psychiatry. 2015;76(3):e351-e358. http://www.ncbi.nlm.nih.gov/pubmed/25830457

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»» Factors related to suicidal behavior in patients with bipolar disorder: the effect of mixed features on suicidality.

Seo HJ, et al. Gen Hosp Psychiatry. 2016;39:91-96. https://www.ncbi.nlm.nih.gov/pubmed/26804773

»» Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features.

Tohen M, et al. J Affect Disord. 2014;164:57-62. http://www.ncbi.nlm.nih.gov/pubmed/24856554

»» Heterogeneity of DSM-IV major depressive disorder as a consequence of subthreshold bipolarity.

Zimmermann P, et al. Arch Gen Psychiatry. 2009;66(12):1341-1352.

RESOURCE CENTER

http://archpsyc.jamanetwork.com/article.aspx?articleid=210481

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Please visit the CLINICAL RESOURCE CENTER for additional information and resources

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