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 This CE activity is supported by
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Janssen Scientific Affairs, LLC,
and from Lilly USA, LLC.
For further information
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The course guide for this
activity includes slides,
disclosures of faculty
financial relationships,
and biographical profiles.

For additional copies of

these materials, please
visit neuroscienceCME.com
or call 877.CME.PROS.
To receive CME/CE credits
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 The faculty have been
informed of their
responsibility to disclose
to the audience if they will
be discussing off-label
or investigational uses
(any use not approved
by the FDA) of products
or devices.
 Moderator:
Paul E. Keck, Jr., MD
President-CEO, Lindner Center of HOPE
Professor of Psychiatry & Behavior Neuroscience
University of Cincinnati College of Medicine
Cincinnati, OH
 Paul E. Keck, Jr., MD
Disclosures
Research/Grants: Alkermes, Inc.; AstraZeneca Pharmaceuticals LP;
Cephalon, Inc.; GlaxoSmithKline; Eli Lilly and Company; EPI-Q, Inc.;
Jazz Pharmaceuticals, Inc.; The Marriott Foundation; National Institute
of Mental Health (NIMH); Orexigen Therapeutics, Inc.; Pfizer Inc.;
Shire Pharmaceuticals
Speakers Bureau: None
Consultant: Bristol-Myers Squibb Company; GlaxoSmithKline; Medco
Health Solutions, Inc.; Pfizer Inc.; Quantia Communications, Inc.;
Schering-Plough Corporation; Sepracor Inc.
Stockholder: None
Other Financial Interests: Employed by the University of Cincinnati
College of Medicine, University of Cincinnati Physicians, and the
Lindner Center of HOPE
Advisory Board: None
Dr. Keck is a co-inventor on United States Patent No. 6,387,956:
Shapira NA, Goldsmith TD, Keck, PE Jr. (University of Cincinnati)
Methods of treating obsessive-compulsive spectrum disorder comprises
the step of administering an effective amount of tramadol to an
individual. Filed March 25, 1999; approved May 14, 2002.
Dr. Keck has received no financial gain from this patent.
 Faculty:
David C. Henderson, MD
Associate Professor of Psychiatry
Harvard Medical School
Director, Schizophrenia, Diabetes, and Weight
Reduction Research Program
Director, The Chester M. Pierce, MD,
Division of Global Psychiatry
Massachusetts General Hospital
Boston, MA
 David C. Henderson, MD
Disclosures
Research/Grants: Johnson & Johnson
Pharmaceutical Research & Development,
L.L.C.; Ortho-McNeil, Division of Ortho-McNeil-
Janssen Pharmaceuticals, Inc.; Takeda
Pharmaceuticals North America, Inc.
Speakers Bureau: None
Consultant: Johnson & Johnson
Pharmaceutical Research & Development,
L.L.C.; Pfizer Inc.
Stockholder: None
Other Financial Interests: None
Advisory Board: None
 Faculty:
Roger S. McIntyre, MD, FRCPC
Associate Professor of
Psychiatry and Pharmacology
University of Toronto
Head, Mood Disorders Psychopharmacology Unit
University Health Network
Toronto, ON
Roger S. McIntyre, MD, FRCPC
Disclosures
Research/Grants: Eli Lilly and Company; Janssen-Ortho, Inc.;
National Alliance for Research on Schizophrenia and Depression
(NARSAD); Shire Pharmaceuticals; Stanley Medical Research
Institute
Speakers Bureau: AstraZeneca Pharmaceuticals LP; Biovail
Pharmaceuticals, Inc.; Eli Lilly and Company; Janssen-Ortho, Inc.;
H. Lundbeck A/S; Wyeth Pharmaceuticals
Consultant: AstraZeneca Pharmaceuticals LP; Bristol-Myers
Squibb Company; Biovail Corporation; H. Lundbeck A/S; Janssen,
L.P.; litigation regarding medication effects; Obecure Ltd.; Otsuka
America Pharmaceutical, Inc.; Pfizer Inc.; Sepracor, Inc.;
Solvay Pharmaceuticals, Inc.; VANDA Pharmaceuticals;
Wyeth Pharmaceuticals
Stockholder: None
Other Financial Interests: None
Advisory Board: AstraZeneca Pharmaceuticals LP; Biovail
Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; Eli Lilly and
Company; France Foundation; GlaxoSmithKline; Janssen-Ortho,
Inc.; H. Lundbeck A/S; Organon; Pfizer Inc.; Schering-Plough
Corporation; Shire Pharmaceuticals; Solvay/Wyeth
Measuring Lipids in Patients
with Bipolar Disorder:
Why We Must
December 1, 2010
 Moderator:
Paul E. Keck, Jr., MD
President-CEO, Lindner Center of HOPE
Professor of Psychiatry & Behavior Neuroscience
University of Cincinnati College of Medicine
Cincinnati, OH
Learning
Objective 1
Identify strategies to
overcome barriers that
hinder lipid measurement
 Learning
Objective 2
Increase the rate at which you
perform at least one assessment for
hyperlipidemia within the initial
16-week treatment period among
patients with BPD who are being
treated with an atypical antipsychotic
agent, in accordance with the STABLE
measure regarding lipid assessment
Learning
Objective 3
Select an appropriate
clinical strategy for
addressing an abnormal
lipid test
 Faculty:
David C. Henderson, MD
Associate Professor of Psychiatry
Harvard Medical School
Director, Schizophrenia, Diabetes, and Weight
Reduction Research Program
Director, The Chester M. Pierce, MD,
Division of Global Psychiatry
Massachusetts General Hospital
Boston, MA
 Faculty:
Roger S. McIntyre, MD, FRCPC
Associate Professor of
Psychiatry and Pharmacology
University of Toronto
Head, Mood Disorders Psychopharmacology Unit
University Health Network
Toronto, ON
 Cardiometabolic
Syndrome(CMS) and
Cardiometabolic Risk
 Clustering of Related Risk
Factors for CVD and Diabetes

Wilson PWF, et al. Circulation 2005;112:3066-3072.

 CMS Definitions

Definitions from 3 major groups

NCEP ATP III1
IDF2
WHO3

WHO = World Health Organization; NCEP ATP III = US National Cholesterol Education
Program Adult Treatment Panel III; IDF = International Diabetes Foundation
See supplemental bibliography for full references.
 NCEP ATP III and IDF
Definitions for CMS
NCEP ATP III1 IDF2
Criterion (When ≥ 3 criteria (Abdominal obesity plus
are present) ≥ 2 other criteria)

Abdominal obesity Caucasian (EU)

South
(waist circumference, inches) Asian/Chinese

Men > 40 ≥ 37 ≥ 35
Women > 35 ≥ 31 ≥ 31
Fasting triglycerides ≥ 150 ≥ 150
(mg/dL) or treatment for this lipid abnormally

HDL (mg/dL)
Men < 40 < 40
Women < 50 < 50
or treatment for this lipid abnormally

Blood pressure (mm Hg) ≥ 130/85 ≥ 130 / ≥ 85

or treatment for previously diagnosed
hypertension

Fasting glucose (mg/dL) ≥ 100 ≥ 100

or previously diagnosed type 2 diabetes

See supplemental bibliography for full references.

 CMS Prevalence in the
General U.S. Population
From NHANES III data, using
definition from NCEP ATP III1
23.7%
Current prevalence estimated to be
higher now due to the unrelenting
increase in the prevalence of
obesity in the general population2

1. Ford ES, et al. JAMA 2002;2873:356-359.

2. Mokdad AH, et al. JAMA 2000;284:1650-1651.
 Increased Cardiometabolic
Risk in Patients with Major
Mental Illness
Epidemiology
Increased prevalence of individual risk
factors, compared to general population1
Obesity
Hyperglycemia
Dyslipidemia
Hypertension
CMS prevalence in bipolar disorder (BPD)
20% - 66%2

1. Newcomer JW. Am J Manag Care 2007;13:S170-S177.

2. McIntyre RS, et al. J Affect Disord 2010;126:366-387.
 Increased Cardiometabolic
Risk in Patients with Major
Mental Illness
Risk Factors
Smoking
Sedentary lifestyle
Use of second-generation
antipsychotic agents (SGAs)

Newcomer JW. Am J Manag Care 2007;13:S170-S177.

 SGAs and
Cardiometabolic Risk
 SGAs Offer Important Benefits
to Patients with BPD...
FDA-Approved Oral SGAs for Adults with BPD
Generic Name Manic Mixed Maint. Depression
Aripiprazole X X X
Asenapine X X
Olanzapine X X X
Quetiapine X X X* X
Risperidone X X
Ziprasidone X X X*
Olanzapine/fluoxetine
X
combination

* Augmentation only
See supplemental bibliography for full references.
...But Have Metabolic Side Effects
FDA alerts and label warning
2004 - FDA has asked manufacturers
of all atypical antipsychotic drugs to
add a new warning to the drugs'
labels about the increased risk of
hyperglycemia and diabetes
FDA has labeled this as a class effect,
although there are major differences
in risk associated with the various
medications
Food and Drug Administration. FDA Patient Safety News: Show #28,
June 2004. http://www.accessdata.fda.gov/psn/printer-full.cfm?id=32.
 Differential Metabolic Side
Effects Among SGAs1-4
Antipsychotic Weight Gain Diabetes Risk Dyslipidemia
Clozapine +++ + +
Olanzapine +++ + +
Risperidone ++ 0 0
Quetiapine ++ 0 0
Aripiprazole ± - -
Ziprasidone ± - -

+ = increased effect
- = minimal effect
0 = discrepant results
See supplemental bibliography for full references.
Learning
Objective 1
Identify strategies to
overcome barriers that
hinder lipid measurement
 Consensus Guidelines
on Metabolic Monitoring
All patients receiving an SGA should
have fasting blood glucose and lipid
levels determined at baseline and after
12 weeks of treatment
ADA/APA Consensus on Antipsychotic Drugs and Metabolic Monitoring
4 8 12 12 5
Start Qtrly
wks wks wks mos yrs
Personal/family hx X X
Weight (BMI) X X X X X
Waist circumference X X
Blood pressure X X X
Fasting glucose X X X
Fasting lipid profile X X X X

American Diabetes Association and American Psychiatric Association.

J Clin Psychiatry 2004;65:267-272.
 Metabolic Monitoring Is
Underperformed in Mental Illness
PharMetrics database study1
Percentage of Patients Prescribed Antipsychotics Who Received
Adverse Effect Testing
July 2000 to Mar 2004 to
Test
Oct 2003 Dec 2006
Baseline lipid level 8.4 10.5
12-week lipid level 6.8 9.0
Baseline glucose level 17.3 21.8
12-week glucose level 14.1 17.9

Medicaid cohort study (N = 109,451)2

Initial testing rates (27% tested for glucose;
10% for lipids) remained unchanged during a period
from January 2002 through December 2005
1. Haupt W, et al. Am J Psychiatry 2009;166:345-353.
2. Morrato EH, et al. Arch Gen Psychiatry 2010;67:17-24.
 Barriers to Monitoring
Lipid Levels
Psychiatric care often conceptualized as
most important form of medical care1
Under awareness of medical burden and
medical risk factor clustering in BPD1,2
Lack of time and resources to address
physical health issues3,4
Offices/clinics not equipped to provide
full medical care and have limited ability
to coordinate off-site care3,4
See supplemental bibliography for full references.
 How can we overcome
barriers to measuring lipids?
Quality Improvement Project
on Metabolic Screening Rates
MGH Outpatient Psychiatry
Resident Clinic
Education
Session Education Education
#1/Supervisor Session #2 Session #3
Memo
Focus LMR/La BMI Feedback
Group bs Table Session

Oct ’08 Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct ’09

B Q1 Q2 Q3 Q4

Wiechers IR, et al. Poster Presented at 2010 Harvard Psychiatry Research

Day Poster Session and Mysell Lecture. March 24, 2010; Boston, MA.
Quality Improvement Project
on Metabolic Screening Rates
Rates of Screening in Patients at Baseline and Quarter 4 (N = 90)

Δ Baseline
Baseline Q4 p-value
to Q4
Ordered glucose 16.7% 45.6% 28.9 < .0001
Ordered lipid panel 13.3% 44.4% 31.1 < .0001
Documented BMI 6.7% 48.9% 42.2 < .0001
Documented glucose 16.7% 58.9% 42.2 < .0001
Documented BP 4.4% 43.4% 39.0 < .0001
Documented lipid panel 17.8% 62.2% 44.4 < .0001
Documented full bundle 1.1% 31.1% 30.0 < .0001

Wiechers IR, et al. Poster Presented at 2010 Harvard Psychiatry Research

Day Poster Session and Mysell Lecture. March 24, 2010; Boston, MA.
 Learning
Objective 2
Increase the rate at which you
perform at least one assessment for
hyperlipidemia within the initial
16-week treatment period among
patients with BPD who are being
treated with an atypical antipsychotic
agent, in accordance with the STABLE
measure regarding lipid assessment
 Bipolar Performance Measures
STABLE* Project

STAndards for BipoLar Excellence

project
Organized in 2005
Evidence-based measures related to
identifying, assessing, managing,
and coordinating care for BPD

* AstraZeneca LLP, Wilmington, Delaware, provided financial sponsorship

for the STABLE Project. They did not otherwise participate in the
development of either the measures or toolkit.
Center for Quality Assessment and Improvement in Mental Health.
The STAndards for BipoLar Excellence Project. Available at:
http://www.cqaimh.org/stable.html.
 STABLE Measure
on Hyperlipidemia Assessment

Perform at least one assessment

for hyperlipidemia within the initial
16-week treatment period among
patients with BPD who are being
treated with an atypical
antipsychotic agent

* AstraZeneca LLP, Wilmington, Delaware, provided financial sponsorship

for the STABLE Project. They did not otherwise participate in the
development of either the measures or toolkit.
Center for Quality Assessment and Improvement in Mental Health.
The STAndards for BipoLar Excellence Project. Available at:
http://www.cqaimh.org/stable.html.
Learning
Objective 3
Select an appropriate
clinical strategy for
addressing an abnormal
lipid test
 When Results Indicate
Hyperlipidemia...
Mental health clinicians can:
Handle themselves
Requires ongoing education on CMS and the
chronic care needs of patients with mental
illness
Work closely with primary care clinician
Such an alliance is useful for many other
issues as well
Requires vigilance in coordination of care
skills
Refer to specialty clinic, if available
There are some
 Handling Yourself?
Worsening dyslipidemia or glycemia
Consider switching SGA
Manage lipids as outlined in NCEP ATP III
Refer patient to ADA self-management
education program
Development of diabetes
Refer to clinician with experience in treating
patients with diabetes
Weight gain ≥ 5% of initial weight
Consider switching SGA

American Diabetes Association and American Psychiatric Association.

J Clin Psychiatry 2004;65:267-272.
 NCEP ATP III
Lipid Level Goals
Target
Lipid
(mg/dL)
LDL Cholesterol < 100
≥ 50 (F)
HDL Cholesterol
≥ 40 (M)
Total Cholesterol < 200
Triglycerides < 150
Grundy SM, et al. Circulation 2004;110:227-239.
National Cholesterol Education Program (NCEP) Expert Panel on
Detection, Evaluation and Treatment of High Blood Cholesterol in
Adults (Adult Treatment Panel III). Circulation 2002;106:3143-3421.
 Positive Predictive Value
of Screening Tests
Positive Predictive
Screening Test
Value
Abdominal obesity for CMS 45.1%
Digital rectal exam for PSA 21%
Fecal occult testing for colon
14%
cancer
Mammography in women
22%
aged 50-59 w/ + family hx

Straker D, et al. Am J Psychiatry 2005;162:127-1221.

 Clinical Connections
Prevalence of CMS is high in the general
population and higher in patients with
major mental illness
Some SGAs are associated with
significant risk of adverse metabolic
changes
 Clinical Connections
Prevalence of CMS is high in the general
population and higher in patients with
major mental illness
Some SGAs are associated with
significant risk of adverse metabolic
changes
Monitoring for metabolic changes in
patients taking SGAs is recommended,
but underperformed
The call to action is to increase
metabolic monitoring in patients with
BPD using practical strategies
 The Medical Health of
Patients with Mental Health
Conditions
“Because several data sets have shown
that guidelines alone do not lead to an
adequate level of monitoring of and
interventions for cardiometabolic risk
factors among patients with severe
mental illness, mental health providers,
patients, and families need to be educated
and medical monitoring and management
need to be an integral part of treating
patients with severe mental illness.”
Correll CU, et al. Psychiatr Serv 2010;61:892-898.
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