A Free, One-Hour CME/CNE/CEP/NASW/CCMC/CPE

Audioconference Series
September–November 2004
Release Date: September 20, 2004
Credit Expiration Date: November 5, 2005
On the Web: www.psychcme.net
presents

The Challenge of Managing

the Complex Clinical
Course of GAD
6903 Rockledge Drive, 8th Floor
c/o CME Outfitters, LLC

This continuing education activity is provided by

Bethesda, MD 20817

CME Outfitters, LLC, gratefully acknowledges an educational grant

from Cephalon, Inc., in support of this CE activity.

TK-005-092004-05

The Challenge of Managing the
Complex Clinical Course of GAD
A Free, One-Hour CME/CNE/CEP/NASW/CCMC/CPE
Audioconference Series
September–November 2004
Release Date: September 20, 2004
Credit Expiration Date: November 5, 2005
On the Web: www.psychcme.net
FACULTY
Martin B. Keller, MD
R. Bruce Lydiard, PhD, MD
psychCME Chair and Moderator
Prakash S. Masand, MD
Syllabus and Course Guide
Presented by
This continuing education activity is provided by
CME Outfitters, LLC, gratefully acknowledges an educational grant
from Cephalon, Inc., in support of this CE activity.
Live, Interactive Sessions (60 minutes)
Please call 800.895.0198 approximately 10 minutes prior to start time
of live sessions.
q September 20, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q September 22, 2004 3:15 p.m. ET/2:15 p.m. CT/1:15 p.m. MT/12:15 p.m. PT
q September 23, 2004 1:15 p.m. ET/12:15 p.m. CT/11:15 a.m. MT/10:15 a.m. PT
q September 28, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q September 29, 2004 5:15 p.m. ET/4:15 p.m. CT/3:15 p.m. MT/2:15 p.m. PT
q October 1, 2004 2:15 p.m. ET/1:15 p.m. CT/12:15 p.m. MT/11:15 a.m. PT
q October 4, 2004 1:15 p.m. ET/12:15 p.m. CT/11:15 a.m. MT/10:15 a.m. PT
q October 5, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q October 7, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q October 12, 2004 3:15 p.m. ET/2:15 p.m. CT/1:15 p.m. MT/12:15 p.m. PT
q October 14, 2004 8:15 p.m. ET/7:15 p.m. CT/6:15 p.m. MT/5:15 p.m. PT
q October 18, 2004 2:15 p.m. ET/1:15 p.m. CT/12:15 p.m. MT/11:15 a.m. PT
q October 19, 2004 1:15 p.m. ET/12:15 p.m. CT/11:15 a.m. MT/10:15 a.m. PT
q October 22, 2004 3:15 p.m. ET/2:15 p.m. CT/1:15 p.m. MT/12:15 p.m. PT
q October 26, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q October 28, 2004 3:15 p.m. ET/2:15 p.m. CT/1:15 p.m. MT/12:15 p.m. PT
q October 29, 2004 1:15 p.m. ET/12:15 p.m. CT/11:15 a.m. MT/10:15 a.m. PT
q November 2, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
q November 3, 2004 1:15 p.m. ET/12:15 p.m. CT/11:15 a.m. MT/10:15 a.m. PT
q November 5, 2004 12:15 p.m. ET/11:15 a.m. CT/10:15 a.m. MT/9:15 a.m. PT
24/7 Dial-In Archive (recorded)
Please call 800.934.7615 any time.
24/7 Web-Based Archive (recorded)
Please visit www.psychcme.net and follow links for psychCME TALK.
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Information for Participants

Statement of Need
Generalized anxiety disorder (GAD) is a chronic and disabling psychiatric disorder
that significantly impairs social and work-related function. Although GAD is treat-
able, less than 30 percent of patients seek treatment. Of those, 50 percent respond to
treatment, but sustaining response and achieving remission can prove challenging
for the clinician. The complex clinical course of GAD leaves many patients falling short
of remission and burdened with persistent residual symptoms. Associated comorbid
physical symptoms and coexisting mood disorders contribute to chronic functional
impairment, can lead to increased medical costs, and can further delay remission. In
this evidence-based psychCME TALK activity, the experts will evaluate the breadth and
impact of GAD as a community health concern, and will discuss current, novel, and
adjunctive therapeutic options for moving patients toward remission and overall bet-
ter outcomes.

Activity Goal
To evaluate the complexity and chronicity of GAD and to discuss effective treatment
strategies in order to improve remission rates and overall patient quality of life.

Learning Objectives
At the end of this CE activity, participants should be able to:
• Review the challenges and complexities associated with the clinical presentation
of GAD, including recognition and diagnosis.
• Discuss and define remission for GAD.
• Analyze current therapeutic options and discuss novel treatments and adjunctive
therapies for GAD.
• Implement a standardized approach to improve recognition and diagnosis of GAD
as well as increase remission rates and patient outcomes.

Target Audience
Physicians, nurses, psychologists, social workers, certified case managers, pharmacists,
and other healthcare professionals with an interest in mental health.

Credit Information
CME Credit (Physicians)
CME Outfitters, LLC, is accredited by the Accreditation Council for Continuing Medical
Education to provide continuing medical education for physicians.
CME Outfitters, LLC, designates this educational activity for a maximum of 1.0 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.

2 www.psychcme.net 3
 The Challenge of Managing the Complex Clinical Course of GAD
CNE Credit (Nurses)
This Educational Activity is presented by CME Outfitters, LLC, which has been
approved as a provider of continuing education by the New York State Nurses
Association, an accredited approver by the American Nurses Credentialing Center’s
Commission on Accreditation. It has been assigned code 5UYSJZ-PRV-0436.
(1.2 contact hours)
CEP Credit (Psychologists)
CME Outfitters, LLC, is approved by the American Psychological Association to offer
continuing education for psychologists. CME Outfitters, LLC, maintains responsibility
for the program. (1.0 CE credits)
NASW Credit (Social Workers)
This program was approved by the National Association of Social Workers (provider
#886407722) for 1 continuing education contact hour.
CCMC Credit (Certified Case Managers)
This program has been approved for 1 hour by the Commission for Case Manager
Certification (CCMC).
CPE Credit (Pharmacists)
CME Outfitters, LLC, is accredited by the Accreditation Council for Pharmacy
Education as a provider of continuing pharmacy education. 1.2 contact
hours (0.12 CEUs)
Universal Program Number: 376-999-04-035-L01 (live interactive session)
376-999-04-035-H01 (recorded activities)
Commercial Support
CME Outfitters, LLC, gratefully acknowledges an educational grant from Cephalon, Inc.,
in support of this CE activity.
Credit Requirements
Successful completion of this CE activity includes the following:
• Participate in the live or recorded educational activity and review the course
materials.
• Complete a credit request form and activity evaluation. Successfully complete the
post-test and record your responses on the credit request form.
• Submit completed forms via FAX to 301.897.3506 or mail to:
CME Outfitters, LLC
6903 Rockledge Drive, 8th Floor
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Attention: Program Registrar
• Questions? Please call 877.CME.PROS.
Forms must be submitted within 30 days of completion of activity. Participants
will receive a certificate or statement of credit within 4–6 weeks following receipt of
the credit request form and activity evaluation form. There is no fee for participation
in this activity. The estimated time for completion of this activity is 60 minutes.
4 www.psychcme.net
The Challenge of Managing the Complex Clinical Course of GAD
psychCME TALK
Faculty Bios & Disclosures
Martin B. Keller, MD
Dr. Keller is the Mary E. Zucker professor and chairman of the Department of
Psychiatry and Human Behavior at the Brown University School of Medicine. He is also
executive psychiatrist-in-chief at the seven Brown University–affiliated hospitals. Dr.
Keller received his medical training at Cornell University, and completed a medical
internship at Bellevue Medical Center in New York City and a psychiatric residence at
Massachusetts General Hospital in Boston.
His research interests include investigation of nosology and long-term course of psy-
chiatric illnesses, including mood disorders, anxiety disorders, and eating disorders,
and the effect of treatment of neuropsychopharmacologic compounds and psy-
chotherapy on the short- and long-term clinical course of these illnesses in children,
adolescents, and adults. One of his methodological contributions to the field has been
the creation of the Longitudinal Interval Follow-Up Evaluation (LIFE), which assesses
psychopathology in detail over long periods of time. The LIFE and its many derivations
have been used by other scientists in over 250 research programs in the U.S. and inter-
nationally.
Dr. Keller has received over 20 research grants from the National Institutes of Health
and numerous grants from research foundations and pharmaceutical industry. He
serves on numerous professional committees and editorial boards, has published over
240 articles for peer-reviewed journals, and has been the recipient of several presti-
gious awards in recognition of making major contributions to the understanding and
treatment of mood disorders. The most recent honor he received is the 2001 American
College of Psychiatrist (ACP) Mood Disorders Lifetime Research Award which he
received in February 2001.
R. Bruce Lydiard, PhD, MD
Dr. R. Bruce Lydiard is director of Southeast Health Consultants, a private research
group in Charleston, which was founded in 2001. Prior to that time, he was profes-
sor of psychiatry at the Institute of Psychiatry, Medical University of South Carolina
in Charleston, where he had been a faculty member for 18 years. He received his
bachelor of arts in psychology, PhD in pharmacology, and doctor of medicine at the
University of Minnesota. He trained in psychiatry at Massachusetts General Hospital,
where he was chief resident in psycho-pharmacology and completed an NIMH-spon-
sored fellowship.
Dr. Lydiard has worked in the areas of the biology and treatment of anxiety and mood
disorders, new drug evaluations, functional gastrointestinal disorders, and the brain-
gut axis. Dr. Lydiard has received NIH funding to study treatment of alcoholics with
panic disorder (NIAAA), the association of irritable bowel syndrome with psychiatric
disorders, victimization and health care utilization (NIMH), and comparative efficacy
of different pharmacological treatments for co-existing panic and major depression
5
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

(NIMH). He has published over 260 papers and book chapters. He is a reviewer for 20 Unlabeled Use Disclosure
journals, and is an associate editor for the Journal of Clinical Psychiatry. Faculty of this CE activity may include discussions of products or devices that are not
currently labeled for use by the FDA. The faculty have been informed of their respon-
Prakash S. Masand, MD, psychCME Chair sibility to disclose to the audience if they will be discussing off-label or investigational
Dr. Masand is Consulting Professor of Psychiatry at Duke University Medical Center uses (any uses not approved by the FDA) of products or devices.
in Durham, North Carolina. He is the section editor for Current Psychiatry Reports and
has published more than 200 articles, abstracts, and book chapters. Dr. Masand is the CME Outfitters, LLC, the faculty, and Cephalon, Inc., do not endorse the use of any
psychCME Chair, host of psychCME TV, and editor of psychCME REPORTS. product outside of the FDA labeled indications. Medical professionals should not uti-
lize the procedures, products, or diagnosis techniques discussed during this activity
without evaluation of their patient for contraindications or dangers of use.
Disclosure Declaration
It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, Activity Slides
and scientific rigor and integrity in all its CE activities. Faculty must disclose to the par- The slides that are presented in this activity are available for download and printout
ticipants any significant relationships with commercial companies whose products or at the psychCME website: www.psychcme.net. Registration is required; please follow
devices may be mentioned in faculty presentations, or with the commercial supporter links for psychCME TALK. Activity slides may also be obtained via fax or email by
of this CE activity. The following information is for participant information only. It is not calling 877.CME.PROS.
assumed that these relationships will have a negative impact on the presentations.
Dr. Keller has disclosed that he receives grants/research support from Eli Lilly, Forest
Laboratories, Merck, Inc., Organon, Pfizer, Inc., and Wyeth Pharmaceuticals. He serves
as a consultant and/or receives honoraria from Bristol-Myers Squibb, Collegium,
Cyberonics, Cypress Bioscience, Eli Lilly, Forest Laboratories, Janssen, Merck, Inc.,
Organon, Otsuka, Pfizer Inc., Pharmacia, Pharmastar, Sepracor, Vela Pharmaceuticals,
Wyeth Pharmaceuticals. Dr. Keller is on the advisory boards of Abbot Laboratories,
Bristol-Myers Squibb, Cephalon, Inc., Cyberonics, Cypress Bioscience, Eli Lilly, Forest
Laboratories, GlaxoSmithKline, Janssen, Merck, Inc., Mitsubishi Pharma Corporation,
Novartis, Organon, Pfizer Inc., Pharmacia, Sanofi-Synthelabo, Scirex, Sepracor, Somerset
Pharmaceuticals, Vela Pharmaceuticals, and Wyeth Pharmaceuticals.
Dr. Lydiard has disclosed that he receives grants from AstraZeneca, Cephalon, Eli
Lilly, GlaxoSmithKline, Janssen, Merck, Neurocrine, Pfizer, Sanofi-Synthelabo, and UCB
Pharma. He is on the speakers bureaus of Cephalon, Eli Lilly, Forest Laboratories,
GlaxoSmithKline, Pfizer, Solvay, and Wyeth-Ayerst. Dr. Lydiard serves as a consultant
to AstraZeneca, Aventis, Cephalon, Eli Lilly, Forest Laboratories, Novartis, Pfizer, Roche
Laboratories, Shire, Solvay, and Wyeth-Ayerst.
Dr. Masand has disclosed that he receives grant and research support from
AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, GlaxoSmithKline, Ortho-McNeil,
Janssen Pharmaceutica, and Wyeth. He is a consultant to Bristol-Myers Squibb, Forest
Laboratories, GlaxoSmithKline, Health Care Technology, Janssen Pharmaceutica,
Organon, Pfizer Inc., and Wyeth. He is on the speakers bureaus of Abbott Laboratories,
AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, Forest Laboratories,
GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer Inc., and Wyeth. Dr. Masand
owns stock in Bristol-Myers Squibb and psychCME, Inc.

6 www.psychcme.net 7
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

psychCME is the evidence-

based series of CE activities
developed at Duke University
Medical Center.

This continuing education

activity is provided by
CME Outfitters, LLC.

CME Outfitters, LLC,

gratefully acknowledges an
educational grant from
The Challenge of Managing Cephalon, Inc.,
the Complex Clinical in support of this CE activity.
Course of GAD

8 www.psychcme.net 9
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

The course guide for this

activity includes slides,
disclosures of faculty financial Please be sure to indicate
relationships, and biographical the media format utilized
profiles. (live interactive session, dial-in
replay, or Internet archive)
For additional copies of these and the date of participation
materials, please visit on the forms provided.
www.psychCME.net or call
877.CME.PROS.

To receive CE credits for this The faculty have been

activity, participants must informed of their responsibility
complete and submit both a to disclose to the audience if
Credit Request Form and an they will be discussing off-label
Activity Evaluation Form, or investigational uses (any use
which are included in the not approved by the FDA)
course materials. of products or devices.

10 www.psychcme.net 11
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

psychCME TALK
Learning Objectives

II. Discuss and define remission

for GAD
The Challenge of Managing
the Complex Clinical
Course of GAD

psychCME TALK psychCME TALK

Learning Objectives Learning Objectives

I. Review the challenges and III. Analyze current therapeutic

complexities associated with options and discuss novel
the clinical presentation of treatments and adjunctive
GAD including recognition therapies for GAD
and diagnosis

12 www.psychcme.net 13
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

GAD Symptoms
psychCME TALK
Learning Objectives
Psychic
Somatic
symptoms symptoms
– worry – muscle tension
IV. Implement a standardized – insomnia – nausea/
– fatigue GI distress
approach to improve – irritability – sweating
recognition and diagnosis – feeling “on edge” – urinary
of GAD as well as increase – poor frequency
concentration – cardiac
remission rates and patient symptoms
outcomes American Psychiatric Association. Diagnostic and Statistical Manual of Mental
Disorders, 4th ed. Washington, DC: American Psychiatric Association; 1994.
Schweizer E, et al. J Clin Psychiatry. 1997;58(suppl 3):27-31.

Generalized Anxiety Disorder Epidemiology of GAD

(GAD)

Lifetime prevalence 5.1%

Excessive or uncontrolled worry
≥ 6 months
Women outnumber men 2:1

Associated physical and psychological
Modal age of onset - early 20s

symptoms
High comorbidity in clinical cases;
1/3 “Pure” in community samples

Causes significant distress or
impairment
Chronic, fluctuating course
(average > 20 yrs)

Symptoms not better explained
Low rate of spontaneous remission
by other condition Kessler RC, et al. Arch Gen Psychiatry. 1994;51:8.
DSM IV-TR. Washington, DC: American Psychiatric Association. 2000. DSM-IV. Washington, DC: American Psychiatric Association, 1994.

14 www.psychcme.net 15
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Diagnostic Dilemma Frequency of Axis I Comorbidity in GAD

Symptom Overlap in GAD and Depression
Intake Prior to and Including Intake
11% 8%
18%
Depression
Agitation GAD 24%
13% 20%

Dysphoria

Interest
Sleep
Nausea/

Fatigue GI distress

Appetite 28%

Concentration
Sweating 19%

Esteem
Restlessness
Muscle tension
30%
29%

Suicide
Irritability
Cardiac

Worry symptoms

Urinary GAD Only
frequency 1 Comorbid Disorder
2 Comorbid Disorders
3 Comorbid Disorders
Roy-Byrne P, et al. J Clin Psychiatry. 1997;58(Suppl 3):34. 4 or More Comorbid Disorders

Potential Somatic Markers Lifetime Prevalence of Comorbid

for Anxiety Disorders Disorders in Patients with GAD
40
35%
35 33% Any Disorder 90.4
31%
30 28%
26% Major Depression 62.4
Prevalence 25
of Anxiety Panic Disorder 23.5
20
Disorders Social Anxiety Disorder 34.4
(%) 15
10 Alcohol Abuse and Dependence 37.6
5 Post-Traumatic Stress Disorder 22.0
0
Chest Pain Fatigue Headache Insomnia Abdominal 0 20 40 60 80 100
Pain % of Patients
Somatic Symptoms (N = 1000)
Kroenke K, Spitzer RL, Williams JBW, et al. Arch Fam Med. 1994;3:774–779. Wittchen HU, et al. Arch Gen Psychiatry. 1994(May);51(5):355-364.

16 www.psychcme.net 17
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Risk of Suicide Attempt Response vs. Remission

HAM-A Total Score Change During Treatment
25 PBO (N = 123)
GAD + MDD
20 Drug X (N = 112)

Odds Ratio
HAM-A 15
(Relative to Response:
MDD Total > 50% decrease
No Mental
Score in HAM-A
Disorder) 10
Remission:
GAD 5 HAM-A < 7

0
0 2 4 6 8 10 0 2 4 6 8 10 12
Week
Wunderlich U, et al. Eur Arch Psychiatry Clin Neurosci. 1998;248:87-95.

Remission Longitudinal Course of

A Clinical Definition Anxiety and Mood Disorders

Two prospective, naturalistic, longitudinal,

Elimination of illness-related multi-center studies of adults with anxiety
impairment / loss of quality of life disorders

Harvard / Brown Anxiety Research

Restoration to a state or wellness-- Project (HARP)
– 711 mental health care patients
as if the person were never ill – Up to 14 years of data

Primary Care Anxiety Project (PCAP)
– 539 primary care patients
– Up to 5 years of data

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 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Methodology Sample Characteristics at Intake

HARP and PCAP

Follow-up interviews utilize the Longitudinal HARP Study PCAP Study
Interval Follow-up Evaluation (LIFE)1 Overall Sample Overall Sample
(N = 711) (N = 539)
– Used to assess the weekly course of disorders Age (M, SD) 40.5 (13.0) 39.09 (11.62)
with psychiatric status ratings (PSRs) as well as Female 66% 76%
psychotropic treatment usage Caucasian 98% 83%
College graduate or better 39% 23%
– Interrater and long-term test-retest (participant Employed full-time 42% 40%
retrospective recall over 1 year) reliability found Comorbid diagnoses (intake):
good-to-excellent reliability2 Major depression 27% 41%
– A separate external validity assessment comparing Panic with agoraphobia 50% 27%
PSRs with other psychosocial measures found good Social anxiety disorder 25% 33%
concurrent and discriminant validity2 PTSD 8% 37%
GAD 25% 26%
1. Keller MB, et al. Arch Gen Psychiatry. 1987;44:540-548.
Panic disorder 12% 17%
2. Warshaw, et al. J Psychiatric Research. 1994;28:531-545. GAF score (M, SD) 60.0 (11.4) 56.8 (8.9)

Definitions of Recovery 10-Year Anxiety Disorder and Major

and Recurrence Depressive Disorder Remission Rates

Recovery MDD (CDS) PD MDD (HARP) GAD PDA SP
1
– 8 consecutive weeks with almost no 0.9 0.93
symptoms of the disorder (PSR 1 or 2) 0.8 0.82
0.7 0.72
Probability 0.6

Recurrence of 0.5 0.50
– After recovery, the re-emergence of Remission 0.4 0.42
0.35
0.3
full criteria symptoms (PSR of 5 or 6) 0.2
for at least 4 weeks (26 weeks for 0.1
GAD) 0
0 1 2 3 4 5 6 7 8 9 10
Years

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 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

10-Year Anxiety Disorder and Major Baseline Predictors of Recovery from GAD
Depressive Disorder Relapse Rates During 4 Years of Follow-Up (PCAP)
PD MDD (HARP) GAD PDA SP
Participants with an older age of GAD onset
1 were more likely to recover
0.9
0.82
(Hazard Ratio = 1.02, p < 0.01),
0.8
0.7
by approximately 2% per year
0.6 0.55
Probability
of Relapse
0.5 0.54
Each ongoing non-psychiatric medical condition
0.4 0.38
0.3 0.34 decreased a participant’s likelihood of
0.2 recovering from GAD by 19%
0.1 (Hazard Ratio = 0.81, p < 0.01)
0
0 1 2 3 4 5 6 7 8 9 10
Years
Primary Care Anxiety Project (PCAP). Data on file.

Summary of GAD Course (HARP) Baseline Predictors of Recovery from GAD

During 4 Years of Follow-Up (PCAP)

Half (cumulative probability of recovery = 0.50)
of the PCAP subjects with GAD recovered
Each lifetime non-psychiatric medical condition
during the ten years of follow-up decreased a participant’s likelihood of

The cumulative probability of recurrence recovering from GAD by 11%
was 0.38 at ten years (Hazard Ratio = 0.89, p < 0.05)

The cumulative probability of recovery
Factors found NOT to be baseline predictors
after recurrence was 0.51 after ten years of GAD recovery
of follow-up – Gender

Thus, GAD appears to have a somewhat – Comorbidity (both # of Axis I disorders
fluctuating course among this sample and specific Axis I mood, anxiety, eating,
and substance use disorders)
of patients
Bruce SE, et al. AJP. (In press). Primary Care Anxiety Project (PCAP). Data on file.

22 www.psychcme.net 23
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Economic Burden of Anxiety Disorders Resource Consumption

Total Costs $42.3 Billion in 1990 by High Utilizers
~ 30% of All Mental Health Costs Highest 10% of Utilizers
Workplace 60 Lowest 50% of Utilizers
Psychiatric 52
Costs
50 48
Treatment 10%
31%
Mortality 40
3% Utilization 29
30
(%)
Medication 18
2% 20
7 9
Medical 10
Treatment
54% 0
Primary Care Visits Specialty Care Hospital Stays
Visits
Greenberg PE, et al. J Clin Psychiatry. 1999;60:427-435. Katon W. J Clin Psychiatry. 1996;57(suppl 10):11–18.

Effect of GAD on Work Impairment Pharmacologic Treatments

50
Goal of treatment: relief of core
45 symptoms and impairment
40
Number 35
Characteristics of ideal medication
with > 6 30 – Rapid onset of action
Days
Impairment/
25 – Few adverse effects
20 – Limited potential for abuse
Loss in Past
Month (%) 15
– Suitable for long-term administration
10
to prevent relapse
5
0
– Convenient
GAD & MDD GAD MDD – Effective in treating both psychic
Wittchen HU, et al. Int Clin Psychopharmacol. 2000;15:319-328.
and somatic symptoms

24 www.psychcme.net 25
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

TCAs Benzodiazepines

Most frequently prescribed drug for GAD

First antidepressants used for GAD – Replaced barbiturates in 1960s
– Efficacious in treating anxiety at doses similar – Pharmacologic gold standard for anxiety Rx
to those for major depression
Advantages
– Alleviate anxiety symptoms

Mechanism: reduce reuptake of serotonin – Rapid onset
or norepinephrine or both – Cost
– High patient acceptance

Available agents: amitriptyline, imipramine, – Efficacy: 65%-75% response
desipramine, nortriptyline
Mechanism
– Increase affinity of GABAA receptors for GABA,
a major inhibitory neurotransmitter in brain

TCAs Benzodiazepines
Drawbacks

Numerous side effects
Not a reliable antidepressant
– Anticholinergic effects

Side effects
– Orthostatic hypotension
– Sedation, fatigue, impaired psychomotor
– Sedation performance, decreased learning ability
– Slowing of cardiac conduction – Synergistic effects with alcohol
– Weight gain

Negative perception among patients/MDs

Extremely dangerous in overdose
Rebound anxiety and withdrawal
symptoms after discontinuation

26 www.psychcme.net 27
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Imipramine, Diazepam, SSRIs in GAD

and Trazodone in GAD Paroxetine: Improvement in Disability
28 PBO (N = 55) Total Family Life Social Life Work
* p < 0.05 0
26 † p < 0.01 Trazodone (N = 61)
Diazepam (N = 56)
24 -1
Imipramine (N = 58)
22 -2
* * *
HAM-A 20 * *
Total Score 18
Change in -3 *

16 † Mean SDS
** -4
14
* * Score from
† * † Baseline -5
12 † † †
† -6
10
0 1 2 3 4 6 8 End * PBO
-7 *
Weeks Point PXT 20mg/day
-8 * p < 0.01 PXT 40mg/day
Rickels K, et al. Arch Gen Psychiatry. 1993;50:884-895. Bellew KM. Poster presented at APA, 2000.

Antidepressants vs. SNRIs in GAD

Benzodiazepines in GAD Venlafaxine XR in Nondepressed Outpatients
30 2'-Chlordesmethyldiazepam (N = 25) 25 Placebo (N = 96)
Imipramine (N = 26) Venlafaxine XR 75mg (N = 86)
25
Paroxetine (N = 30)
Adjusted 20 Venlafaxine XR 150mg (N = 81)
Mean 20 Mean Venlafaxine XR 225mg (N = 86)
HAM-A HAM-A *†
15
Total Total
* * 15
Score 10 Score
*
‡†
5 * *† †
* p < 0.05 10
0 0 1 2 3 4 5 6 7 8
0 2 4 6 8 Weeks
Weeks p < 0.05 for ‡75mg, *150mg, and †225mg vs. PBO
Rocca, et al. Acta Psychiatr Scand. 1997;95:444. Rickels K, et al. Am J Psychiatry. 2000;157:968-974.

28 www.psychcme.net 29
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Novel Pharmacologic Options Tiagabine vs. Paroxetine in GAD

30

Selective GABA reuptake inhibitors Baseline
– GABAA-receptor modulators 25
24.4 Endpoint
– α2δ ligands 22.5

20

Cholecystokinin (CCK) receptor antagonists HAM-A *
– CCK neurotransmitter found in gut and brain Total 15 13.8
*
– Interacts with other neuronal systems to cause Score 10.7
anxiety 10

Neurokinin 5
– NK2 receptor antagonists have an anxiolytic-like
effect in rodents 0
* p < 0.05 Tiagabine Paroxetine
– No published human data in GAD
No significant difference between treatments

Newer agents with high affinity for 5-HT1A This information concerns a use that has not been approved by the FDA

binding sites Rosenthal M. J Clin Psychiatry. 2003;64:1245-1249.

Selective GABA Reuptake Inhibitors in GAD Selective GABA Reuptake Inhibitors in GAD
Tiagabine: HAM-A Total Scores α2δ Ligands: Pregabalin
Weeks
0 1 2 3 4 6 8
Final
Visit

Structurally related to GABA
0 † (2-dimensionally)
-2 PBO
Mean -4

Biolocial activity resembles L-leucine
Tiagabine
Change -6
Binds with high selectivity and affinity to α2δ
in *
HAM-A
-8 subunit of voltage-dependent Ca2+ channels
-10
Total
-12
6 out of 7 placebo-controlled studies show
Score
-14 positive results
* p < 0.05 *
-16

Does not yet have FDA approval
† Final visit was calculated using last post-baseline observation for each patient
This information concerns a use that has not been approved by the FDA
Rickels K. Poster presented at APA, 2002.
Van Ameringen M, Pollack MH, et al. Poster presented at CINP, 2004. Kasper S. Poster presented at NCDEU, 2002.

30 www.psychcme.net 31
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Cognitive Behavioral Treatment Basics Combined Treatments in GAD

Rationale
6-month post-taper evaluation

Combined treatment > diazepam alone

Self-monitoring but not > CBT

Identify maladaptive coping styles
All active treatments > PBO but not
different from each other

Identify distorted cognitions
Response rates (2SD change from BSL)
– Combined CBT + DZ - 95%

Establish hierarchy of fears and exposures – Combined CBT + PBO - 83%
– CBT only - 71% (superior to DZ alone)

Long-term benefits maintained after – DZ only - 68%
discontinuation Power, et al. J Anxiety Disorders. 1990;4:267.

Psychotherapy in GAD 8- to 14-Year Follow-Up

100 Recovery Rates at 6 Months
of CBT Treatment of GAD
90 Long-Term
80 Pre-Treatment Follow-Up Mean
70 HAM-A N Mean (SD) (SD)
60%
60
51% CBT alone 7 14.7 (3.4) 7.9 (3.1)
% of
Patients
50 CBT + DZ 8 12.9 (5.8) 9.1 (6.5)
40 CBT + PL 4 16.0 (4.1) 9.0 (6.7)
30 CBT group 19 14.2 (4.6) 8.6 (5.2)*
20
DZ only 7 13.4 (6.4) 11.4 (5.6)
10 4%
PL only 3 16.7 (2.1) 10.3 (7.5)
0
Cognitive Applied Relaxation Analytical Non-CBT 10 14.4 (5.6) 11.1 (5.8)
Behavioral Therapy Psychotherapy
* Paired comparison, p < 0.001 for CBT group
Fisher PL, et al. Psychol Med. 1999;29:1425-1434. Durham, et al. Psychological Medicine. 2003;33:499-509.

32 www.psychcme.net 33
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Strategies for Refractory Clinical Pearls

Anxiety Disorder Treatment

Optimize treatment intensity
TCAs, SSRIs, SNRIs, and 5-HT1A agonists
all are effective

Combine antidepressant with BZ
or GABAergic AEDs
Rationale polypharmacy is not a bad
choice

Other combination pharmacotherapy

CBT is an effective treatment

Add CBT

Intervention may prevent comorbid

Review psychosocial variables depression

Clinical Pearls
Recognition and Diagnosis

Ask about worry or stress
if unexplained
– Headache
– Fatigue
www.psychCME.net
– Muscle tension
– Sleeping disturbance
– GI distress

34 www.psychcme.net 35
 The Challenge of Managing the Complex Clinical Course of GAD The Challenge of Managing the Complex Clinical Course of GAD

Post-Test
6. True or False: In 1990, 42.3 billion dollars were spent on anxiety disorders, which
accounted for 30% of total mental health care costs.
A. True
Participants are required to complete the post-test to assess their achievement B. False
of the educational objectives for this activity. To obtain a certificate or statement of
credit, you must complete the post-test and indicate your answers on the Post-Test 7. In order to effectively treat GAD, an ideal pharmacological medication is necessary.
Responses section found on the credit request form. You must complete both this Which of the following characteristics should be considered when choosing an ideal
post-test and the evaluation to receive credit. A score of 70% is required for credit. medication?
A. Gradual onset of action
The Challenge of Managing the Complex Clinical Course of GAD B. Efficacy in treating somatic symptoms only
1. Generalized anxiety disorder (GAD) can be characterized by which of the following? C. Suitability for long-term administration (to help prevent relapse)
A. Significant distress or impairment D. All of the above
B. Excessive or uncontrolled worry lasting 6 months or more E. None of the above
C. Associated physical and psychological symptoms
8. Tricyclic antidepressants (TCAs) can be used to treat GAD. Which of the following is
D. All of the above
NOT included in the TCA side effect profile?
E. None of the above
A. Anticholinergic effects
2. GAD can be diagnosed by the presence of both psychic and somatic symptoms. B. Weight reduction
Examples include which of the following? C. Orthostatic hypotension
A. Psychic symptoms such as muscle tension, nausea, and GI distress D. Slowing of cardiac conduction
B. Somatic symptoms such as insomnia, fatigue, and irritability E. None of the above
C. Psychic symptoms such as insomnia, fatigue, and irritability
9. In addition to pharmacotherapy, cognitive behavioral therapy (CBT) can be used to
D. None of the above
help treat patients with GAD. Which of the following best describes the advantages
of CBT?
3. True or False: According to epidemiological statistics, women are twice as likely as men
to have GAD. A. Identifies maladaptive coping styles
A. True B. Identifies distorted cognitions
B. False C. Establishes a hierarchy of fears and exposures
D. All of the above
4. Many symptoms of GAD can overlap with symptoms of depression. Examples of these E. None of the above
overlapping symptoms include which of the following?
A. Sleep and fatigue 10. Which of the following strategies can be used for refractory anxiety disorder?
B. Tension and worry A. Add CBT
C. Restlessness B. Minimize treatment intensity
D. All of the above C. Maintain monotherapy treatment regimen
E. None of the above D. All of the above
E. None of the above
5. Which of the following series of statistics best describes the lifetime prevalence
of disorders comorbid with GAD?
A. Panic disorder, 12%; post-traumatic stress disorder, 23.5%; major depression, 48.4%
B. Panic disorder, 23.5 %; post-traumatic stress disorder, 22%; major depression, 62.4%
C. Panic disorder, 48.4%; post-traumatic stress disorder, 62.4%; major depression, 12%
D. Panic disorder, 62.4%; post-traumatic stress disorder, 12%; major depression, 23.5%
E. None of the above

36 www.psychcme.net 37
 TK-005-092004-05

CE Credit Request Form

This continuing education
The Challenge of Managing the activity is provided by
Complex Clinical Course of GAD
A CE Audioconference Series • September–November 2004
To receive CE credit, you must complete both this form and an evaluation form, and return the completed
forms via mail to CME Outfitters, 6903 Rockledge Drive, 8th Floor, Bethesda, MD 20817; or, FAX to
301.897.3506 for fastest service. Forms must be submitted within 30 days of completion of activity. A cer-
tificate or statement of credit will be mailed to you within 4–6 weeks of our receiving this form and the evaluation
form.
PLEASE PRINT CLEARLY (Form must be filled out completely to process certificate)
First Name, MI, Last Name: ______________________________________________________________________
Specialty Area: _______________________________________________________________________________
I am a: q U.S. Licensed Physician q Nurse q Psychologist
q Social Worker q Pharmacist q Other_________________________________
Degree: q MD q DO q PhD q NP q RN q PharmD q MSW q Other ____________
I participated in a: q LIVE interactive session q Dial-in replay q Internet archive
Participation Date: ________ / ________ / ____________________
Complete Mailing Address: _____________________________________________________________________
City: _____________________________________________________State:____________Zip: ______________
Business Phone: __________________________ Email: _____________________________________________
Type of CE Credit Requested: q CME/Physicians (max. 1.0 ________ ) q CNE/Nurses (1.2)
q CEP/Psychologists (1.0) q NASW/Social Workers (1.0)
q CPE/Pharmacists (1.2) q Others (1.0 CME Attendance Certificate)
NOTE: Unless requesting multiple types of CE credit, Certified Case Managers are only required to complete the attached CCMC
Verification of Completion and CE Activity Evaluation forms.

Please see pages 3–4 for credit information and requirements.

How long did it take you to complete this activity?_________ hours ________ minutes
Post-Test Responses (Enter letter of correct response; 70% score required for credit):
1. ________ 2. ________ 3. ________ 4.________ 5.________
6. ________ 7. ________ 8. ________ 9.________ 10._______
How did you learn about this continuing education event?
q Brochure/direct mail q Brochure/from rep q Email
q Internet q Colleague recommended q Other: ________________________________
Please rate your interest in participating in future psychCME educational activities
(1=highly interested, 5=uninterested): ______
What formats do you prefer for learning? (Please rank the top three; 1 = most preferred):
_____ Symposium ____ Audioconference ____ Internet ____ CD-ROM
_____ Journal ____ Satellite Broadcast ____ Monograph ____ Other: __________
As a result of my participation in this activity, I will commit to:
• Sharing information from this activity with staff and colleagues. q Yes q No
• Utilizing the assessment tools described in this activity to develop
an individualized management/care plan for each of my patients. q Yes q No
• Analyzing overall improvement in patient management/care
through use of the therapeutic options described in this activity. q Yes q No
Commercial supporters occasionally ask for a participant list (name, city, state) for internal outcomes research
only. No promotional materials will be sent to you as a result of being on this list.
q Do not include my name on this list.

Signature: ______________________________________________________ Date: ______________________

 TK-005-092004-05

CE Activity Evaluation
This continuing education
The Challenge of Managing the activity is provided by
Complex Clinical Course of GAD
A CE Audioconference Series • September–November 2004
To receive CE credit, you must complete both this form and a credit request form, and return the com-
pleted forms via mail to CME Outfitters, 6903 Rockledge Drive, 8th Floor, Bethesda, MD 20817; or, FAX
to 301.897.3506 for fastest service. Forms must be submitted within 30 days of completion of activity.
A certificate or statement of credit will be mailed to you within 4–6 weeks of our receiving this form and the
credit request form.
1. The content level was: q Too easy q About right q Too difficult
Strongly Agree Strongly Disagree
2. Objectives were related to the overall purpose/goal of the 5 4 3 2 1
activity (to evaluate the complexity and chronicity of GAD and to
discuss effective treatment strategies in order to improve remission
rates and overall patient quality of life).
3. The course met the stated objectives:
• Review the challenges and complexities associated with the 5 4 3 2 1
clinical presentation of GAD, including recognition and diagnosis.
• Discuss and define remission for GAD. 5 4 3 2 1
• Analyze current therapeutic options and discuss novel treatments 5 4 3 2 1
and adjunctive therapies for GAD.
• Implement a standardized approach to improve recognition and 5 4 3 2 1
diagnosis of GAD as well as increase remission rates and patient
outcomes.
4. The educational materials were useful. 5 4 3 2 1
5. The visual aids (presentation slides) were useful and appropriate. 5 4 3 2 1
6. The overall activity was excellent. 5 4 3 2 1
7. The physical environment was conducive to learning. 5 4 3 2 1
8. Rate the quality of the faculty member(s) listed below, from 5 (Excellent) to 1 (Poor):
Clinical Teaching Level of
Speaker Content Relevance Strategies Expertise
Martin B. Keller, MD 5 4 3 2 1 5 4 3 2 1 5 4 3 2 1 5 4 3 2 1
R. Bruce Lydiard, PhD, MD 5 4 3 2 1 5 4 3 2 1 5 4 3 2 1 5 4 3 2 1
9. Will you change the way you practice based on this activity? q Yes q No
If no, is it because you already practice this way? q Yes q No
If no, please explain:______________________________________________________________________
10. Do you feel the activity was balanced and objective? q Yes q No
If no, please state reasons: _________________________________________________________________
11. Do you feel the activity was free of commercial bias? q Yes q No
If no, did it negatively impact the educational value of this activity? q Yes q No
If yes, please state reasons: ________________________________________________________________
______________________________________________________________________________________
12. What was the most useful information you gained from this activity? _____________________________
______________________________________________________________________________________
13. Suggested topics for future activities: _______________________________________________________
______________________________________________________________________________________
14. General comments/suggestions: ___________________________________________________________
______________________________________________________________________________________
15. I participated in a: q LIVE interactive session q Dial-in replay q Internet archive
16. Participation date: ________ / ________ / ____________________
17. I am a: q U.S. Licensed Physician q Nurse q Psychologist q Social Worker
q Case Manager q Pharmacist q Other_______________________
Thank you for your feedback. Your comments will be reviewed carefully and
ultimately used to guide the development of our future continuing education activities.
 TK-005-092004-05

Note: ONLY Certified Case Managers wishing

to receive CCMC credit for this activity should
fill out and return this form. Please send
completed form to the address listed below,
NOT to CME Outfitters, LLC.

FOR CERTIFIED CASE MANAGER USE ONLY

CCMC
VERIFICATION OF COMPLETION
(Please Print or Type All Information)

SPONSOR INFORMATION (To be completed by program/activity sponsor.)

CME Outfitters LLC 00063520
Sponsoring Organization Sponsor Code

6903 Rockledge Dr - 8FL Richard Vanderpool

Street Address Contact Person

Bethesda MD 20817 301.214.8972

City/State/Zip Code Phone Number for Contact Person

PROGRAM/ACTIVITY INFORMATION (To be completed by program/activity sponsor.)

The Challenge of Managing the Complex Clinical Course of GAD - various 2004
Program/Activity Title
Through 12/31/04
Program/Activity Date or Date of Completion
6352024186 1.00
Approval Number Clock Hours Attended/Completed

9/20/04
Signature of Individual in Charge of Verifying Attendance/Completion Date of Signature

PARTICIPANT INFORMATION (To be completed by participant prior to submission.)

Name Certificate Number

Street Address Daytime Telephone Number

City/State/Zip Code

To have these clock hours added to your CCM certification file, please send a copy of this form
to CCMC, 1835 Rohlwing Road, Suite D, Rolling Meadows, IL 60008. It is best to submit
this documentation as activities are completed or at least on an annual basis. This form is for
pre-approval by CCMC only and will only be added to your certification file with them. If you
hold certification from other organizations, you will need to submit verification of attendance/
completion according to their requirements.
 TK-005-092004-05

psychCME TALK Audioconferences

Attendance Form for Groups
Please complete and FAX to 301.897.3506

Audioconference Title and Faculty:

The Challenge of Managing the Complex Clinical Course of GAD,
with Martin B. Keller, MD, and R. Bruce Lydiard, PhD, MD

Site/Institution Name: _________________________________________________

q Community Mental Health q State Mental Health
q Private Practice q Primary Care q Other:
Practice Setting: ______________________________________________________

Address: ____________________________________________________________

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Phone: ________________________________ Fax:__________________________

Email:_______________________________________________________________

q Check here to receive a free CD + monograph of this CE activity.

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___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

___________________________ MD RN Pharm Other: ______________

Please FAX completed form to 301.897.3506 and use additional sheets as necessary.
Questions? Call 877.CME.PROS. Thank you for participating in psychCME TALK!