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Title: PRELOAD


1
PRELOAD
  • load website or connect
  • load Zyban pdf
  • psyched, presentations, pdf, page 10
  • load MDQ
  • Get Pointer

2
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.

4
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)

5
Cain et al, 2005
  • The Dirt on Coming Clean Perverse Effects of
    Disclosing Conflicts of Interest

6
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

7
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8
Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
9
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10
BP II depression hypomania
11
Hospitalization Psychosis
12
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13
Guy?
14
Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
15
Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
16
Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold BP NOS
17
Time Symptomatic
Depression Plus
18
The Bipolar Mood Spectrum
19
Unipolar
Bipolar
Unhappy Appetite/weight changes Disturbed
sleep Poor concentration Suicidal
ideation Fatigue
Unhappy Appetite/weight changes Disturbed
sleep Poor concentration Suicidal
ideation Fatigue
20
All your depressed patients what percentage
are bipolar? (and may therefore have seriously
adverse reactions to antidepressants)
21
Of your last 100 depressed patients, how many
were unipolar or bipolar?
Angst J et al. J Affect Disord, 2003
22
91
23
91
31
24
1-year Prevalence, NCS-R
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
25
1-year Prevalence, NCS-R
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
26
1-year Prevalence, NCS-R
6.7 ------------------------------- 2.8
21 - 31 UPBP
Merikangas, Akiskal, Angst, Kessler, Hirshfeld,
et al Arch Gen Psych, 2007
27
Bipolar Disorders
Mood
Bipolar I
Time
Mood
Bipolar II
Mood
Sub-threshold
28
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29
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

30
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.    
31
E.g. Zyban
32
Mood Disorders Questionnaire(MDQ)
33
Modified MDQ
  • Scoring
  • Website
  • Alternative DIGFAST

34
MDQ accurate enough?
35

MDQ accurate enough?
Phelps J, Ghaemi N Predictive Value of
Bipolar Screening Tests Journal of
Affective Disorders, 2006
36
Memory Lane.
37
Memory Lane.
38
Predictive Values
Phelps/Ghaemi, 2006
39
Predictive Values
Prior Probability
(hunch)
Phelps/Ghaemi, 2006
40
Predictive Values
Prior Probability
(hunch)
Phelps/Ghaemi, 2006
41
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42
  • 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
43
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
44
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
45
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46
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

47
3-5 Minute Diversionfor Advanced Practitioners
  • (hold on)

48
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49
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50
McElroy et al
51
Bipolar Mixity
  • Mackinnon Pies. Bipolar Disorder, 2006

52
  • Mackinnon Pies. Bipolar Disorder, 2006

53
Bipolar Mixity
  • Mackinnon Pies. Bipolar Disorder, 2006

54
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55
Lab test?
56
Phillips et al, ISBD 2007
fMRI Ventral striatum and amygdala
Control
Bipolar Unipolar
57
Differential this
58
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?
59
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60
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

64
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
66
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67
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

68
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

69
RCTs of Long-term Antidepressants in BP
Ghaemi NS. Antidepressants in Bipolar Disorder
Primary Psychiatry 2006, online
70
Antidepressants v. placebo in bipolar depression
Percent Durable Recovery
bupropion paroxetine
versus placebo
Sachs G et al, New England Journal of Medicine,
April 2007
71
Antidepressants v. placebo in bipolar depression
Sachs G et al, New England Journal of Medicine,
April 2007
72
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?

73
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?

74
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).
  •  

77
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
78
Antidepressants - How much bipolarity before
caution? - Default diagnosis bipolar - 9
Alternatives
79
9 Antidepressant Modalities - RCT evidence for
efficacy - Not likely to worsen cycling
80
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81
A Fifth Photoreceptor
82
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83
Psychotherapy Data
84
Psychotherapy Data
85
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.
86
Time to recovery among 293 bipolar depressed
patients assigned to intensive psychosocial
intervention or collaborative care
30
50
Miklowitz, D. J. et al., 2007.
87
Common Elements
  • PsychoEducation
  • Adherence
  • Cognitive
  • Behavioral
  • Exercise
  • Regularity
  • Family

88
Common Elements
  • PsychoEducation
  • Adherence
  • Cognitive
  • Behavioral
  • Exercise
  • Regularity
  • Family

Psychotherapy (December 11, 12, 13 -- M, E, P)
89
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
91
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

92
(No Transcript)
93
3 Tools
94
Texas Bipolar Depression Algorithm
95
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.
96
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

98
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
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