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The Bipolar Spectrum in Primary Care Diagnosis
and Management
Jim Phelps, M.D.PsychEducation.org
3

• Jim Phelps, M.D. credibility?
• Phelps JR and Ghaemi SN. Improving the Diagnosis
  of Bipolar Disorder Predictive Value of
  Screening Tests. Journal of Affective Disorders,
  March 2006.
• Phelps J, Angst J, Katzow J, Sadler J. Validity
  and Utility of the Bipolar Spectrum Model.
  Bipolar Disorders, in press.
• Phelps J. Bipolar Spectrum, in Parker G, ed.,
  Bipolar II Disorders Modelling, Measuring and
  Managing. Cambridge Univ. Press, in press.
• Phelps J. Why Am I Still Depressed? Recognizing
  and Managing the Ups and Downs of Bipolar II and
  Soft Bipolar Disorders. McGraw Hill, 2006.

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The Bipolar Spectrum in Primary Care Diagnosis
and Management

• Speakers bureau/ honoraria GlaxoSmithKline,
  AstraZeneca
• No consultancies McGraw-Hill royalties
• PsychEducation.org -- free, no data storage
  this slide program
• (Off-label use of medications extensive,
  data-driven)

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Cain et al, 2005

• The Dirt on Coming Clean Perverse Effects of
  Disclosing Conflicts of Interest

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Outline

• Diagnosis
• Phenomenology, prevalence, spectrum perspective
• Soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• 9 antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
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BP II depression hypomania
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Hospitalization Psychosis
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Guy?
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Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
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Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
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Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
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Time Symptomatic
Depression Plus
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The Bipolar Mood Spectrum
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Unipolar
Bipolar
Unhappy Appetite/weight changes Disturbed
sleep Poor concentration Suicidal
ideation Fatigue
Unhappy Appetite/weight changes Disturbed
sleep Poor concentration Suicidal
ideation Fatigue
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All your depressed patients what percentage
are bipolar? (and may therefore have seriously
adverse reactions to antidepressants)
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Of your last 100 depressed patients, how many
were unipolar or bipolar?
Angst J et al. J Affect Disord, 2003
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91
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91
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1-year Prevalence, NCS-R
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
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1-year Prevalence, NCS-R
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
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1-year Prevalence, NCS-R
6.7 ------------------------------- 2.8
21 - 31 UPBP
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
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Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold
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Outline

• Diagnosis
• Phenomenology, prevalence, spectrum perspective
• Soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• 9 antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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March 22, 2004 children
Antidepressant Warning template
May 2, 2007 ages 18-24
patients should be adequately screened to
determine if they are at risk for bipolar
disorder Such screening should include a
detailed psychiatric history, including a family
history of suicide, bipolar disorder, and
depression.    
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E.g. Zyban
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Mood Disorders Questionnaire(MDQ)
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Modified MDQ

• Scoring
• Website
• Alternative DIGFAST

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MDQ accurate enough?
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MDQ accurate enough?
Phelps J, Ghaemi N Predictive Value of
Bipolar Screening Tests Journal of
Affective Disorders, 2006
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Memory Lane.
37
Memory Lane.
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Predictive Values
Phelps/Ghaemi, 2006
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Predictive Values
Prior Probability
(hunch)
Phelps/Ghaemi, 2006
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Predictive Values
Prior Probability
(hunch)
Phelps/Ghaemi, 2006
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• Fam Hx Bipolar
• Onset lt Age 25
• Repeated Episodes
• (Seasonality)
• Depressions Atypical
• Brief Episodes
• Psychosis
• Post-partum Depression
• 3 or More AntiDepressants
• Loss of Response to AD
• Hypomania on ADs

Ghaemi, Ko, Goodwin Can J Psychiatry
2002 (website link)
Bipolar Soft Signs
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Bipolarity Index Do you have Bipolar Disorder?
How bipolar are you?

• Hypomania/Mania 20 points
• Family History 20 points
• Age of Onset 20 points
• Course of Illness 20 points
• Response to Rx 20 points

Sachs, 2004
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1. MDQ - 2. Fam Hx plus Timeline
4. Number of episodes (many, or few)
5. Response to antidepressants Loss of response,
gt3
3. Age of onset Atypical, post-partum,
seasonal, psychotic
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Outline

• Diagnosis
• Phenomenology, prevalence, spectrum perspective
• Soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• 9 antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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3-5 Minute Diversionfor Advanced Practitioners

• (hold on)

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McElroy et al
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Bipolar Mixity

• Mackinnon Pies. Bipolar Disorder, 2006

52

• Mackinnon Pies. Bipolar Disorder, 2006

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Bipolar Mixity

• Mackinnon Pies. Bipolar Disorder, 2006

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Lab test?
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Phillips et al, ISBD 2007
fMRI Ventral striatum and amygdala
Control
Bipolar Unipolar
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Differential this
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Differential Diagnosiswhat else looks like
bipolar disorder?

• Mood thyroid, normal
• Attention sleep deprivation, ADHD
• Anxiety Generalized Anxiety, PTSD, all
• Substance Abuse uppers, downers
• Personality Disorder Cluster B (dramatic)
• Psychosis schizophrenia, substance use
• Delirium medical illness, medications

Mimic? Comorbid? Component?
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Differential Diagnosiswhat else looks like
bipolar disorder?

• Mood thyroid, normal
• Attention sleep deprivation, ADHD
• Anxiety Generalized Anxiety, PTSD, all
• Substance Abuse uppers, downers
• Personality Disorder Cluster B (dramatic)
• Psychosis schizophrenia, substance use
• Delirium medical illness, medications

Think Treatment
Mimic? Comorbid? Component?
61
Differential Diagnosiswhat else looks like
bipolar disorder?

• Mood thyroid, normal
• Attention sleep deprivation, ADHD
• Anxiety Generalized Anxiety, PTSD, all
• Substance Abuse uppers, downers
• Personality Disorder Cluster B (dramatic)
• Psychosis schizophrenia, substance use
• Delirium medical illness, medications

Psychotherapy (December 11, 12, 13 -- M, E, P)
62
1. MDQ - 2. Fam Hx plus Timeline
4. Number of episodes (many, or few)
5. Response to antidepressants
3. Age of onset
63
Outline

• Diagnosis
• Phenomenology, prevalence, spectrum perspective
• Soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• 9 antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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Then A Miracle Occurs
65
Glutamate
Cortisol
GR
NMDA
BAG-1
Ca
NE
Glucose Transporter
PKA
ROS
CREB
Bcl-2
Bad
PTP
Akt
GSK-3ß
valproate
PI-3-k
MAP/ERK
lithium
TrkB
Serotonin
BDNF
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Gene knockout unleashes manic mouse

• Roybal et al. Mania-like behavior induced by
  disruption of CLOCK. Proc Natl Acad Sci U S A.
• 
  April 2007

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Outline

• Diagnosis
• Phenomenology,prevalence, spectrum perspective
• MDQ, soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• 9 antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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RCTs of Long-term Antidepressants in BP
Ghaemi NS. Antidepressants in Bipolar Disorder
Primary Psychiatry 2006, online
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Antidepressants v. placebo in bipolar depression
Percent Durable Recovery
bupropion paroxetine
versus placebo
Sachs G et al, New England Journal of Medicine,
April 2007
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Antidepressants v. placebo in bipolar depression
Sachs G et al, New England Journal of Medicine,
April 2007
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Antidepressant Controversies in Bipolar Disorder
Treatment

• 1. Cause switching? How often?
• 2. Mood destabilization
• a) Prevent stabilization?
• b) Cause rapid cycling?
• c) Cause kindling?
• 3. Already on, and a mood stabilizer, and doing
  well when to taper off? Leave on?

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Antidepressant Controversies in Bipolar Disorder
Treatment

• 1. Cause switching? How often?
• 2. Mood destabilization
• a) Prevent stabilization?
• b) Cause rapid cycling?
• c) Cause kindling?
• 3. Already on, and a mood stabilizer, and doing
  well when to taper off? Leave on?

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The Kindling model
75
Psychotherapy
Hypothetical Is this happening? Even rarely?
Antidepressant and subsequent mania
76
(unedited entire quote)

• In 2005 I was in my late 20s and had never
  suffered mania.  I had been diagnosed with
  depression and anxiety, but not
  bipolar disorder.  I was prescribed Lexapro for
  anxiety (I had never used psychiatric medication
  before) and used it for five or six days (half
  tablet each day).  It induced mania so I was
  hospitalized for a week or so.
•  
• Since then, I have steadily had irrational
  grandiose thoughts.  In hindsight, I can see that
  I had some irrational grandiose thoughts before
  my Lexapro use, but since my Lexapro use they are
  far stronger.  As far as permanence goes, so
  far I have not noticed any improvement at all
  coming simply from time passing (although therapy
  and other active approaches have been helpful).  
  I had a second manic episode in early 2006 (I was
  not on any medication at the time).
•  

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Frederick Goodwin, M.D.
- Manic-Depressive Illness, 1990/2007- former
head of NIMH
Doctors think of antidepressants as light,
easy, uncomplicated drugs and mood stabilizers
as heavy drugs that should be reserved as a last
resort. But in fact, recent data suggest that we
may have to reverse that order of preference, or
at least put them on an equal plane.
Primary Psychiatry, 2005
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Antidepressants - How much bipolarity before
caution? - Default diagnosis bipolar - 9
Alternatives
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9 Antidepressant Modalities - RCT evidence for
efficacy - Not likely to worsen cycling
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A Fifth Photoreceptor
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Psychotherapy Data
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Psychotherapy Data
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Time to recovery among 293 bipolar depressed
patients assigned to intensive psychosocial
intervention or collaborative care
Miklowitz, D. J. et al. Arch Gen Psychiatry 2007.
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Time to recovery among 293 bipolar depressed
patients assigned to intensive psychosocial
intervention or collaborative care
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Miklowitz, D. J. et al., 2007.
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Common Elements

• PsychoEducation
• Adherence
• Cognitive
• Behavioral
• Exercise
• Regularity
• Family

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Common Elements

• PsychoEducation
• Adherence
• Cognitive
• Behavioral
• Exercise
• Regularity
• Family

Psychotherapy (December 11, 12, 13 -- M, E, P)
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David Miklowitz, Ph.D.
One-Book EducationBipolar I

• the Bipolar Disorder Survival GuideWhat you and
  your family need to know

90
One-Book EducationBipolar II
www.PsychEducation.org
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Outline

• Diagnosis
• Phenomenology,prevalence, spectrum perspective
• MDQ, soft signs, Harvards Bipolarity Index
• Mixed states, differential diagnosis
• Treatment
• Antidepressants in bipolar disorder
• Nine antidepressants that arent antidepressants
• Bipolar-specific psychotherapies
• Medication options

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3 Tools
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Texas Bipolar Depression Algorithm
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Texas Bipolar Depression Algorithm
Taking Li
Taking no antimanic, with history of severe
and/or recent mania
Taking no antimanic, without history of severe
and/or recent mania
Taking otherantimanic
Increase to 0.8 mEq/L
(continue)
Stage 1
antimanic lamotrigine
lamotrigine
Stage 2
olanzapine/fluoxetine or quetiapine
Adapted from Suppes T, et al. J Clin Psychiatry.
200566870-886.
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Texas Bipolar Depression Algorithm
Taking Li
Taking no antimanic, with history of severe
and/or recent mania
Taking no antimanic, without history of severe
and/or recent mania
Taking otherantimanic
Increase to 0.8 mEq/L
(continue)
Stage 1
antimanic lamotrigine
lamotrigine
Stage 2
olanzapine/fluoxetine or quetiapine
Adapted from Suppes T, et al. J Clin Psychiatry.
200566870-886.
97
Prescribing

• Diagnosis
• Document TSH
• Buy-in
• Education family?
• Lifestyle
• alcohol/drugs, sleep
• Pregnancy
• 3 Tools or Menu

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pro's

con's
99
- How much bipolarity before caution? -
Default diagnosis bipolar
100
1. MDQ - 2. Fam Hx plus Timeline
4. Number of episodes (many, or few)
5. Response to antidepressants
3. Age of onset