rethinking bipolar disorder: where we've been, where we are,...

Rethinking Bipolar Disorder:

Where We've Been, Where We

Are, Where We Need to Go

page 85 in syllabus

David J. Kupfer, MD

Professor, Department of Psychiatry

Professor of Neuroscience and Clinical and Translational Science,

Center for Neuroscience, University of Pittsburgh School of Medicine

Chair, DSM-5 Task Force

Sponsored by the Neuroscience Education Institute

Additionally sponsored by Fairleigh Dickinson University School of Psychology

This activity is supported by educational grants from: Lilly USA, LLC; Otsuka America Pharmaceutical, Inc.; Pamlab, L.L.C.; Sunovion Pharmaceuticals Inc.;

Takeda Pharmaceuticals International, Inc., U.S. Region and Lundbeck Pharmaceutical Services, LLC; Teva Pharmaceutical Industries Ltd. with additional support from: Assurex Health, Inc.; JayMac Pharmaceuticals, LLC; Neuronetics, Inc.. For further information concerning Lilly grant funding, visit www.lillygrantoffice.com.

Copyright © 2013 Neuroscience Education Institute. All rights reserved.

Individual Disclosure Statements

Faculty Author / Presenter

David J. Kupfer, MD, is a professor in the department of psychiatry and a

professor of neuroscience and clinical and translational science in the

center for neuroscience at the University of Pittsburgh School of Medicine,

PA.

Consultant/Advisor: Servier (spouse)

Dr. Kupfer reports receiving consulting fees from the American Psychiatric

Association for serving as the Chair of the DSM-5 Task Force.

Contributing Author

Ellen Frank, PhD, is a Distinguished Professor of Psychiatry and a

professor of psychology in the department of psychiatry at the University of

Pittsburgh School of Medicine, PA.

Consultant/Advisor: Servier

Copyright © 2013 Neuroscience Education Institute. All rights reserved.

Learning Objectives

• Describe reasons for combined psychotherapy and

medication management in bipolar patients

• List the main treatment targets of one evidence-

based psychotherapy for bipolar disorder –IPSRT

• Describe the primary medical comorbidities that put

bipolar patients at medical risk

• Identify treatment approaches to bipolar patients

based on the stage of illness

Individuals with bipolar disorder typically spend

the majority of their lives:

1. In a euthymic state

2. In a subsyndromally manic or hypomanic state

3. In a subsyndromally depressed state

4. In a syndromally depressed state

Pretest Question 1

The most common co-morbidities with bipolar

disorder are:

1. Anxiety and substance use disorders

2. Substance use and eating disorders

3. Anxiety and eating disorders

4. Eating disorders and ADHD

Pretest Question 2

The most common medical comorbidities with

bipolar disorder are:

1. Cancer

2. Cardiovascular disease

3. Osteoporosis

4. Eczema

Pretest Question 3

Rethinking Bipolar Disorder

• Where have we been?

• Where are we now?

• Where do we need to go?

Myths

1. Uncommon disorder

2. Presents mostly as mania

3. Onset usually at middle age

4. Lithium-responsive disease with a full

restoration of functioning

5. Lack of comorbidity

6. The major concern for mortality is suicide

• Epidemiological Catchment Area Study1

− Lifetime prevalence: 1.2%

− (3.3 million people in US)

• National Comorbidity Survey2

− Lifetime prevalence: 1.6%

− (4 million people in US)

• National Comorbidity Survey – Replication3

− Lifetime Prevalence (BI-II): 3.9%

• Equal sex distribution1

1. Goodwin FK, Jamison KR. Manic Depressive Illness, 1990. 2. Kessler RC et al. Arch Gen Psychiatry 51:8-19, 1994. 3. Kessler RC et al. Arch Gen Psychiatry 62:593-602, 2005.

Uncommon

Symptom free

Depressive symptoms

Manic/hypomanic

symptoms

Cycling/mixed symptoms Prospective Study N=146, follow-up > 12 years

Weekly affective symptom

status ratings

Judd LL et al. Arch Gen Psychiatry 59:530-537, 2002.

Long-term Symptomatic Status of

Patients With Bipolar I Disorder

1. Post et al. Clin Neurosci Res 2:142-157, 2002.

2. Ketter et al. J Clin Psychiatry 63:146-151, 2002.

It Is Important to Recognize and

Treat Bipolar Depression

• Bipolar depression is more pervasive than mania1

• Mean duration of the depressive episode in bipolar

disorder is longer than manic episodes2

• Depression is chronic in more than 20% of patients with

bipolar disorder2

• Recently introduced medications (anticonvulsants and

atypical antipsychotics) have predominantly antimanic

rather than antidepressant properties2

Kupfer DJ et al. Acta Neuropsychiatrica 12:110-114, 2000.

*p

Treatment of Bipolar Depression

• Whether or not to use an antidepressant

• How long is long enough?

• Guideline recommendations (2–6 months)

• Is risk of cycling increased?

• Discontinuation risks

Age of First Onset

0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45+

%

0

5

10

15

20

25

30 Men Women

Age of first onset

Mean = 19.8 Median = 17.5

Kupfer DJ et al. J Clin Psychiatry 63:120-125, 2002.

Distribution of Age of First Onset

Major Goals of Treatment in

Bipolar Disorder

• Prevent future episodes of mania

• Prevent mixed episodes

• Prevent episodes of depression

• Diminish the presence of subsyndromal

depression over extended periods of time

• Improve functioning

• Decrease morbidity and mortality

"I cannot imagine leading a normal life without

both taking lithium and having had the benefits of

psychotherapy…ineffably, psychotherapy heals. It

makes some sense of the confusion, reigns in the

terrifying thoughts and feelings, returns some

control and hope and possibility of learning from it

all…It is where I have believed—or have learned

to believe—that I might someday be able to

contend with all of this."

- Kay Jamison, Ph.D., An Unquiet Mind, 1995

Why Treat Bipolar Disorder With

Psychotherapy?

• Increase adherence to medication

• Enhance social and occupational functioning

• Enhance capacity to manage stressors in the social-occupational milieu

• Enhance protective effects of family and other social supports

• Decrease denial and trauma and encourage acceptance of the disorder

• Decrease the risk of recurrence

Swartz HA, et al. Psychotherapy for bipolar disorder. In: American Psychiatric Publishing Textbook of Mood

Disorders. DJ Stein, DJ Kupfer & AF Schatzberg (eds.) American Psychiatric Press Publishing, 405-420, 2006.

Empirically Tested Psychotherapies for

Bipolar Disorder

• Cognitive Behavioral Therapy (CBT)

• Psychoeducation (Group)

• Psychoeducation (Individual)

• Family Focused Therapy (FFT)

• Interpersonal and Social Rhythm Therapy

(IPSRT)

1. Simon et al. Arch Gen Psychiatry 63:500-508, 2006.

2. Torrent et al. Am J Psychiatry 170:852-859, 2013.

Other Currently Available

Psychosocial Approaches

• Systematic core management1

• Functional remediation2

STEP-BD Psychosocial Treatment of

Acute Depression: Study Design

• 293 acutely depressed patients with bipolar I or II

disorder were randomly assigned to intensive

treatment (up to 30 sessions of FFT, CBT, or IPSRT

over 9 months) or a brief control treatment (CC)

• Each site provided 2 of the intensive treatments and

the CC

• Only patients with family members were eligible for

assignment to FFT

• Primary outcome: time to "recovered" status (< 2

moderate symptoms for 8 weeks)

0 200 250 300 350 400 50 100 150

0.0

0.2

0.4

0.6

0.8

1.0

Cu

mu

lati

ve

Pro

po

rtio

n n

ot

Re

co

ve

red

Days to Recovered Treatment Intensive Psychosocial Intervention Collaborative Care

Time to Recovered Status: Intensive Treatments vs. Control

LogRank Chi square = 6.93, P = 0.009

Miklowitz et al. Arch Gen Psych 64:419-426, 2007.

Miklowitz et al. Arch Gen Psych 64:419-426, 2007.

Time to Recovered Status: Individual Treatments vs. Control

Empirically Tested Psychotherapies for

Bipolar Disorder

• Cognitive Behavioral Therapy (CBT)

• Psychoeducation (Group)

• Psychoeducation (Individual)

• Family Focused Therapy (FFT)

• Interpersonal and Social Rhythm Therapy

(IPSRT)

Essential Elements of Interpersonal and

Social Rhythm Therapy (IPSRT)

• Social rhythm therapy¹

– Regularizes daily routines

– Emphasizes link between mood and regular routines

– Uses Social Rhythm Metric to monitor routines

• Interpersonal psychotherapy²

– Emphasizes link between mood and life events

– Focuses on interpersonal problem areas (grief, role transition, role disputes, interpersonal deficits)

1. Frank E et al. Biol Psychiatry 2000;48:593-604; Frank E et al. Arch Gen Psychiatry 62:996-1004, 2005.

2. Klerman GL et al. Interpersonal Psychotherapy of Depression, Basic Books, New York, 1984.

Maintenance Therapies in

Bipolar Disorder Study Design

Acute Treatment Maintenance Treatment

IPSRT and

protocol pharmacotherapy

IPSRT and


Strategy #1

ICM and


ICM* and


Strategy #2

ICM and


IPSRT and


Strategy #3

IPSRT and


ICM and


Strategy #4

Patient enters study

and is randomly assigned

* ICM = Intensive Clinical Management

FPC = Functional Principal Components

Interpersonal and Social Rhythm Therapy

0 10 20 30 40

0

2

4

6

Weeks in acute phase

SRM

scores

FPC1: 85% FPC2: 8%

Intensive Clinical Management

0 10 20 30 40

0

2

4

6

Weeks in acute phase

SRM

scores

FPC1: 75% FPC2: 19%

SRM = Social Rhythm Metric

Effect of Acute Treatment Assignment on Change in SRM Scores

Frank E et al. Arch Gen Psychiatry, 62:996-1004, 2005.

Maintenance Therapies in Bipolar

Disorder: Key Outcomes

• Acute IPSRT was associated with significantly greater (more rapid) improvement in occupational functioning and...

• Significantly longer survival without a new mood episode in the maintenance phase, regardless of maintenance treatment assignment (p = 0.01)

• Participants in IPSRT had significantly higher regularity of daily routines (p < 0.001)

• Increased regularity of daily routines in the acute phase was associated with a reduced risk of relapse in the maintenance phase (p < 0.05)

Frank et al. Arch Gen Psychiatry, 2005; Frank et al. Am J Psychiatry, 2008.

Treatment of Bipolar Disorder:

Current Summary (1)

• Overall, advances in drug treatment remain

quite modest

• Antipsychotic drugs are effective in the acute

treatment of mania; their efficacy in the

treatment of depression is variable, with the

clearest evidence for quetiapine

• Despite the widespread use of antidepressants,

considerable uncertainty and controversy

remains about the use of antidepressants in the

management of depressive episodes

Adapted from Geddes et al., The Lancet 381:1672-1682, 2013.


Current Summary (2)

• Lithium has the strongest evidence for long-term

relapse prevention; the evidence for

anticonvulsants such as divalproex and

lamotrigine is less robust, and there is much

uncertainty about the longer-term benefits of

antipsychotics

• Substantial progress has been made in the

development and assessment of adjunctive

psychosocial interventions

Adapted from Geddes et al. Lancet 381:1672-1682, 2013.


Current Summary (3)

• Long-term maintenance and possibly acute

stabilization of depression can be enhanced by

the combination of psychosocial treatments and

drugs

Adapted from Geddes et al. Lancet 381:1672-1682, 2013.

Bipolar Disorder

The Perpetual Co-traveler

With Other Disorders

Bipolar Disorder

• Considerable psychiatric comorbidity

• Substance abuse

• Medical disorders

• Medical "risk factors" (smoking, obesity)

JAMA 293:2528-2530, 2005.

Standardized Mortality Ratio (SMR) of Patients With Unipolar Disorder (N = 147)

vs. Bipolar Disorder (N = 158)

Unipolar (UP) Bipolar (BP) UP vs. BP

(t-test)

P-value

Observed Deaths

SMR Observed

Deaths SMR

Cardiovascular 40 1.36 59 1.84*

Mortality in Bipolar Disorder

Cause of Death Observed Expected Mortality

Deaths* Deaths** Ratio

Suicide 15.7 0.67 23.4

Cardiovascular causes 42.1 14.0 3.0

Respiratory causes 33.3 1.08 3.1

472 Bipolar Patients

* % study group

** % Registrar General's figures

Adapted from: Sharma R & Markar HR. J Affective Disord 31:91-96, 1994.

Mortality and General Medical Healthcare Severely Compromised in Bipolar Disorder

Patients with bipolar disorder (N=15,386) followed for 10 years (average). Mental disorder=dementia, drug or alcohol addiction, psychosis.

Ösby U et al. Arch Gen Psychiatry 58:844-850, 2001; Druss BG et al. Arch Gen Psychiatry 58:565-572, 2001.

2.0

2.5

3.2

4.0

4.8

14.2

22.0

1.9

3.4

4.4

5.0

15.0

2.4

3.2

2.3

3.3

3.7

10.3

1.9

3.1

0 5 10 15 20 25

Cerebrovascular

Cardiac

Respiratory

Accident

Infection

Mental Disorder

Traffic Accident

Homicide

Undetermined Violent Death

Suicide

Men

Women

Standardized Mortality Ratio

Prevalence of Comorbidities Among Patients

With a Diagnosis of Bipolar I Disorder

Compared to the VA National Population

Comorbidity % Mean Age %

Mean Age P-value

Hypertension 34.4 57 36.8 64 0.0066

Diabetes 17.1 58 15.6 64 0.0038

Hepatitis C 5.8 47 1.1 49 0.00002

Lower back pain

15.0 51 10.6 55 0.00002

COPD 11.1 60 9.4 67 0.007

Bipolar I Disorder General Population

COPD = chronic obstructive pulmonary disease

Kilbourne A et al. Bipolar Disord 6:368-373, 2004.

Time to Depressive Recurrence C

um

ula

tive

Pro

po

rtio

n

Rem

ain

ing

Wel

l

Weeks in Maintenance Treatment

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60 80 100 120

Nonobese

Obese

Obese patients had a shorter time to depressive recurrence than nonobese patients

Fagiolini A et al. Am J Psychiatry 160:112-117, 2003.

Log Rank Chi-square = 7.33, df = 1, p < 0.007)

Obesity in Bipolar Disorder

• 68% overweight, 32% met criteria for obesity (relative to

< 20% of controls) (Fagiolini et al., 2003)

– Shorter time to relapse, particularly into depression

– More previous episodes

• 58% overweight, 21% obesity (McElroy et al., 2002)

– Arthritis

– Hypertension

– Diabetes mellitus

• Quality of life (Fontaine & Bartlett, 1998)

• Social life (Wolf & Colditz, 1996)

• Self-esteem (Kawachi, 1999)

Adapted from Harvey AG 2005.

Obesity and Its Longitudinal Course in

Bipolar Disorder

• The association between obesity and increased

prospective depressive burden appears to be

explained by baseline demographic variables

• In contrast, obesity independently predicts the

accumulation of medical conditions among

adults with BD

• Treatment of obesity could potentially mitigate

the psychiatric and medical burden of BD

Adapted from Goldstein et al. Bipolar Disorders 15:284-293, 2013.

Medical Risk Profile for Bipolar Disorder

Obesity

Smoking

"Metabolic Syndrome"

Metabolic Syndrome

"Metabolic syndrome" is the presence of 3 or more

of the following characteristics:

• Abdominal obesity (waist circumference)

• Hypertriglyceridemia

• Low high-density lipoprotein cholesterol (HDL-C)

• High blood pressure

• Fasting hyperglycemia

Adapted from: Fagiolini et al. Bipolar Disord 7:424-430, 2005.

Prevalence of Metabolic Syndrome

in Patients With Bipolar Disorder (N = 441)

Criterion Description %

MS 1 Waist circ. > 40 in. (men) or > 35 in. (women) 51

MS 2 Triglycerides > 150 mg/dL 47

MS 3 HDL < 40 mg/dL (men) or < 50 mg/dL (women) or being on cholesterol-lowering medication

45

MS 4 Systolic bp > 130 mm/Hg and diastolic bp > 85 mmHg or being on blood pressure medication

55

MS 5 Fasting glucose > 110 mg/dL or being on a glucose-lowering drug

19

MS At least 3 of MS 1 – MS 5 40

Fagiolini et al. J Clin Psychiatry 69:678-679, 2008.

Model of Bipolar Disorder

Modifiable Medical

Risk Factors

Sleep–Wake and

Social Rhythms

Medical Diseases

Bipolar Symptoms

Functioning

• Multidisciplinary treatment team (CRNP,

psychiatrist, internist, and lifestyle coach)

• Individual lifestyle interventions

• Early intervention for medical risk factors and

disease

• Efforts to increase adherence to medical and

psychiatric treatment

• Psychopharmacological management that takes

risks and diseases into account

An Integrated Care Model for

Bipolar Disorder

Premature Mortality From General Medical Illness

Among Persons With Bipolar Disorder: A Review

• Cardiovascular disorder appeared to be the most consistent cause of excess mortality in larger studies

• Patients with bipolar disorder face a greater risk of death from medical illness than the general population

• Studies suggest that an unhealthy diet, binge eating, lack of exercise, substance abuse, and/or delaying medical care can lead to premature death

Roshanaei-Moghaddam B & Katon W. Psychiatric Services 60:147-159, 2009.

Goldstein et al. Bipolar Disord 2009.

Cardiovascular Disease and Hypertension

Among Adults With Bipolar I Disorder O

dd

s R

atio

(ad

just

ing

fo

r ag

e, s

ex,

and

rac

e)

• Excessive obesity, hypertension, and diabetes

• Obesity is associated with psychiatric hospitalization, polypharmacy, substance abuse, physical abuse, minority race

• Increased sensitivity to metabolic side effects of mood-stabilizing medications

• Cardiometabolic problems often precede treatment for bipolar disorder

Adapted from Goldstein BI 2011; Goldstein et al. J Clin Psychiatry 2008; Evans-Lacko et al. J Clin

Psychiatry 2009; Jerrell et al. J Clin Psychiatry 2010; Correll et al. Bipolar Disord 2010.

Cardiovascular Risk Among Youth

With Bipolar Disorder

Why Is the Risk of Cardiovascular

Disease Increased in Mood Disorders?

Cardiovascular risk

Platelet

aggregation

Inflammation HPA

dysregulation

Endothelial

dysfunction

Adrenergic

hyperactivity Genetics e.g., CACNA1C

Adapted from Goldstein BI 2011; Kupfer. JAMA 2005; Frasure-Smith & Lesperance. Can J Psychiatry 2006.

Future Directions (1)

• Identification of subgroups with circadian

fragility or vulnerability

• Identification of subgroups most "prone" to

develop a high metabolic risk profile

Future Directions (2)

• How do we prevent acute illness from becoming

chronic?

• Can early intervention prevent "comorbid

accumulation"?

Time to Challenge Our View of

Bipolar Disorder?

Leboyer & Kupfer. J Clin Psychiatry 2010;71:1689.

A cyclical illness

characterized by full-blown

manic or depressive

episodes interspaced with

normal euthymic periods

Traditional perspective Modern holistic perspective

A subtle chronic

progressive multisystem

disorder

Manic

phase

Depressed

phase

Cognitive

function

Comorbid disorders

Cardiovascular disease

Cerebrovasular disease

Diabetes mellitus

Obesity

Hypertension Bipolar

disorder

STRESS

SLEEP & CIRCADIAN DYSFUNCTION

AUTOIMMUNE DISORDER

RETROVIRUS

BRAIN & PERIPHERAL IMMUNO-INFLAMMATION

Genetic Risk Factors

Environmental Risk Factors

Oxidative Stress

Apoptosis Cell Damage

Figure 1: Different mechanisms that might cause abnormal immuno-inflammation and inactivity with genetic susceptible background and environmental factors will lead to bipolar disorder best conceptualized as a multisystem disorder

Bipolar Disorder: From a Mental to a Multisystem Disorder

Ada

pted

from

Mar

ion

Lebo

yer,

2013

.

Bipolar Disorder (BP): A Heterogeneous Disorder

BP characteristics Age at onset Polarity of episodes Delusions

Physiopathology Polygenic Environment

Interepisode profile Sleep and circadian Emotion reactivity Cognition Comorbid disorders

Regions of interest Hippocampus Amygdala Prefrontal area

Lithium and other mood stabilizers

Overlap between psychiatric disorders: MDD, schizoaffective, schizophrenia, autism….

At risk to be handicapped: staging

Ada

pted

from

Mar

ion

Lebo

yer,

2013

.

Taking a Broader View:

Interepisodic Symptom Domains

Traditional

perspective Diagnostic and statistical

manuals of mental

disorders have focused

on major

mood episodes

Modern holistic perspective

Interepisodic dysfunctional

symptom domains need to

be considered

Psychiatric and medical

comorbid disorders

Abnormal emotional reactivity

Sleep and circadian rhythm

disturbances

Cognitive impairment


Abnormal Emotional Reactivity:

Brain Imaging Impaired neural networks subserving emotional regulation

Hypoactivation of response

inhibition to emotion (in red, cingulate cortex and basal ganglia)

fMRI emotional go / no-go

in euthymic bipolar patients

Overactivation of brain

structures mediating

automatic emotion recognition (in blue, oribitofrontal cortex)

Wessa et al. Am J Psychiatry 2007;164:638; Houenou et al. Mol Psychiatry 2008.

Evidence of altered emotional processing

Several genes important

in sleep and circadian

systems have been associated

with bipolar disorder

(TIMELESS, CLOCK, ARNTL)

Sleep and circadian rhythm disturbances should

be assessed throughout the course of illness

and treated to prevent relapse

Sleep and circadian rhythm

disturbances

induce mood episodes

Evidence suggests weak

coupling of circadian system to

external environment

Euthymic bipolar patients show: Variability in sleep duration

Circadian rhythm instability

Low and delayed melatonin peak

Interepisodic Symptom Domains: Sleep and Circadian Rhythm Disturbances

Harvey et al. Am J Psychiatry 2005;162:50; Mansour et al. Ann Med 2005;37:196;

Harvey. Am J Psychiatry 2008;165:820; Leboyer & Kupfer. J Clin Psychiatry 2010;71:1689.

Delayed verbal memory is the

best cognitive predictor of poor

functional outcomes

Martinez-Aran et al. Bipolar Disord 2007;9:103; Goodwin et al. Eur Neuropsychopharmacol 2008;18:787;


Regular assessment of cognitive impairment

is needed during follow-up to plan

personalized cognitive remediation

Patients with bipolar disorder

have cognitive impairment in

attention, memory, and

executive function

Some cognitive impairments

appear early in the course of

illness and persist over time in

euthymic patients

Interepisodic Symptom Domains: Cognitive Impairment

Preliminary evidence of

accelerated cognitive decline

as disorder progresses

Cardiovascular

disease

Cerebrovascular

disease

Diabetes

mellitus

Obesity

Hypertension Bipolar

disorder

Bipolar Disorder: From a Mental to a Multisystem Disorder

Interepisodic Symptom Domains: Medical Comorbidity

● Greater risk of cardiovascular mortality associated with bipolar disorder

(1.5–2.5X) than schizophrenia or unipolar depression

● Under-recognition of medical disorder and risk factors has a major

impact on outcome


Psychiatric assessment

Risk factor assessment

– Weight, BMI, hypertension,

glucose tolerance, lipids,

C-reactive protein

Summary: Assessment and Treatment

of Interepisodic Symptom Domains Domain Assessment

Abnormal emotional

reactivity

Cognitive

impairment

Sleep and circadian

rhythm disturbances

Psychiatric and medical

comorbidities

Treatment

BMI, body mass index

Affective Lability Scale

Affect Intensity Measure

Sleep diary

Pittsburgh Sleep Quality

Index

Neuropsychological

assessment

Stress management

Relaxation

Treatment to be developed

Psychoeducation

Interpersonal and social

rhythm therapy

Cognitive behavioral

therapy

Cognitive remediation

Treatment of comorbid

psychiatric and medical

disorders

Diet, exercise, and

smoking cessation…

Patient follow-up is pivotal; also important to consider

benefit-risk profile of current or planned psychotropic medication


Clinical Staging Framework for Bipolar Disorders (1)

Clinical

Stage Characteristics

Target

Populations

Potential

Interventions

0

Increased risk of bipolar

disorder

No symptoms currently

First-degree relatives of

patients with bipolar

disorder

Improved mental health,

family education, drug

education, brief social

rhythm training

1a Mild or non-specific

symptom

Screening of teenage

populations, referral by

primary care

physicians, referral by

school counselors

Psychoeducation, active

substance abuse

reduction

1b

Ultra high risk: moderate

but subthreshold

symptoms, with

neurocognitive changes

and functional decline to

caseness

Psychiatric intervention

Family psychoeducation,

active substance abuse

reduction, atypical

antipsychotic agents for

episode, antidepressant

agents or mood

stabilizers

Adapted from McGorry et al. Aust N Z J Psych 2006.

Clinical Staging Framework for

Bipolar Disorders (2)

Clinical


Target

Populations

Potential

Interventions

2

First episode of bipolar

disorder

Full threshold disorder

with moderate to severe

symptoms,

neurocognitive deficits

and functional decline

Referral by primary

care physicians,

emergency

departments,

specialist care

agencies, drug and

alcohol services

Family

psychoeducation,

active substance

abuse reduction,

atypical antipsychotic

agents for episode,

antidepressant agents

or mood stabilizers


Clinical


Target

Populations

Potential

Interventions

3a

Incomplete remission from

first episode

Could be linked or fast-

tracked to Stage 4

Primary and specialist

care services

Additional emphasis on

medical and psychosocial

strategies to achieve full

remission

3b

Recurrence or relapse of

psychotic or mood disorder

that stabilizes with

treatment, residual

symptoms, or

neurocognition below the

best level achieved

following remission from

first episode

Primary and specialist

care services

Additional emphasis on

relapse prevention and

"early warning signs"

strategies

4

Severe, persistent illness

judged by symptoms,

neurocognition, and

disability criteria

Specialized care

services

Emphasis on integrated

medical/psychiatric care


Clinical Staging Framework for Bipolar Disorders (1)

Bipolar Disorder:

How Can We Do Better?

Today

A major public health concern but underfunded and under-

investigated

Often diagnosed with delay, inaccuracy, and poor

management of comorbid conditions

A heterogeneous, complex, multisystem disorder

Tomorrow, we should improve…

…course of disease via early, accurate, and thorough diagnosis

…prognosis via personalized therapeutic strategies

…monitoring of medical risk factors and comorbid conditions

Leboyer and Kupfer, J Clin Psy, 2010

Individuals with bipolar disorder typically spend

the majority of their lives:

1. In a euthymic state

2. In a subsyndromally manic or hypomanic state

3. In a subsyndromally depressed state

4. In a syndromally depressed state

Posttest Question 1

The most common co-morbidities with bipolar

disorder are:

1. Anxiety and substance use disorders

2. Substance use and eating disorders

3. Anxiety and eating disorders

4. Eating disorders and ADHD

Posttest Question 2

The most common medical comorbidities with

bipolar disorder are:

1. Cancer

2. Cardiovascular disease

3. Osteoporosis

4. Eczema

Posttest Question 3

rethinking bipolar disorder: where we've been, where we are,...

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