Transcript Hantouche, Pan Arab Psych, Beirut, Nov 2014

Neo-Hippocratic Classification
of Bipolar Disorders
Elie-G. HANTOUCHE
Anxiety & Mood Center
www.ctah.eu
IRPB, Lisboa – April 26-28, 2015
Caring for Bipolar Patients
• Recognition of the bipolar spectrum and its
underlying impact
• Treatment selection
– There are no short term treatments
– May need integrated treatments
• Use the patient’s life system (temperament)
• Teach/learn to anticipate
• The goal is collaborative mastery
Hantouche, Pan Arab Psych, Beirut, Nov 2014
Strategy and Time Course
Acute
Continuation
Maintenance
0-8 weeks
1-6 months
Indefinite
Symptomatic
recovery
Maximize moodstabilizers;
adjunctive
treatments
Support/structure;
education; involve
family
Functional
recovery
Optimize
tolerability; taper
adjunctive when
possible
Behavioral
systems; institute
monitoring
Maximized
function; stability
Optimize;
anticipate
prodromes
Strategies to
optimize
adaptation
Hantouche, Pan Arab Psych, Beirut, Nov 2014
MANIA
ROOTS Of
BIPOLARITY
MDE
WINGS OF
BIPOLARITY
Hantouche, International BP Meeting, Budapest, September 2005,
Central Role of Temperaments
in Mood Disorders
- Specifiers of bipolarity
- Risk factors (interface between
vulnerability and episodes)
- Early stages of the illness
- Major determinants for distinction
between “episodic” vs “unstable” BP
- Factors influencing clinical expressions,
evolution and response to treatment
Hantouche, Pan Arab Psych, Beirut, Nov 2014
Apparent Spectrum
of Illness Course
Purely Episodic Course:
- Inter-episode stability
- No mixed states
- Infrequent episodes
- Good recovery
- Low incidence of
complications
Radical Mood Instability:
- Inter-episode instability
- Mixed states
- Frequent episodes
- Incomplete recovery
- High incidence of
complications
- Early onset
- Stronger genetic loading?
Swann, 5th IRBD, LYON 2005
President: J Angst Bureau: E Hantouche,
G Perugi, A Erfurth
Viarregio 2005
Photo by E Hantouche
“Intra-Bipolar” Dichotomy
(hypo)manic Episodes
Stable Hyperthymic Temperament
Free Intervals
Major Depressive Episodes
Unstable Cyclothymic temperament
Hypomanic Episodes
Major Depressive Episodes
as developed by EBF – Viareggio 2005
Intra-Bipolar (BP-I) Dichotomy:
Temperamental influence
Hyperthymic / stable
Males
Late onset
Manic episodes
Hospitalizations
Drug abuse
Antisocial behaviors
Cyclothymic / instable
Females
Young onset
Separation anxiety
Anxious-impulsive comorbidity
Borderline features
FH Bipolar + Anxiety Dis.
Suicide behaviors
Perugi, SOPSI, Rome 2008
Dominant
Impact on Psychopathology
Temperament and Personality (NEO) in Youth
Cyclothymic /
Irritable
Poor Prognosis / Impaired Functioning
Positive correlation with
- Current Depressive intensity, Megalomania,
Grandiosity, Impulsivity,
- Borderline features
- High level of Neuroticism
Negative correlation with
- Agreeableness and Conscientiousness
Hyperthymic
Positive correlation with
- Bipolar Spectrum, Hypomania, Megalomania,
Grandiosity, Impulsivity
- Extraversion / Openness
Depressive
Positive correlation with
- Depressive symptoms
- Neuroticism / Agreeableness
Walsh MA, JAD, 2012
Treating Bipolarity
Hippocratic
Anti-Hippocratic
Prediction of response to
Stabilizers begins with
Clinical Assessment and
Observation
Atypical
Neuroleptic
Lithium
Lamotrigine
None / Psychosis /
Non Episodic dis
Episodic Bipolar /
Unipolar dis
Anxiety disorders
Addictions
Yes
No
Yes
Polarities (m,d)
Mostly M
Mostly D
Mostly D
Acute presentation
Atypical
Typical
Atypical
Comorbidity
Common
Rare
Very frequent
Childhood
psychopathology
Common
Absent
Very frequent,
abuse common
MMPI profile
Abnormal
Normal
Abnormal
Dissociated
Episodic
Dissociated
Responder to
Family History
Residual symptoms
Daily symptoms
Bipolar Subtypes meeting DSM-IV criteria
Psychotic BD:
“Schizo-Bipolar”:
NL / AAP
Typical BD: “ManicDepression”: Li
Characterological BD:
“Bipolar Temperament”:
LTG
Alda M Eur Neuropsychopharmacol. 2004;14 S94-9.
Excellent Lithium Response
• Patients in whom monotherapy with
lithium can completely prevent
further recurrences of manic and
depressive episodes (Grof, 1999)
• About 1/3 of lithium treated bipolar
patients (Rybakowski et al., 2001)
• Episodic clinical course, complete
remission, bipolar family history,
and low psychiatric comorbidity
(Grof, 2010)
2013; 145: 187-189.
TEMPS-A and Lithium Response
Correlations between
temperaments
and quality of lithium
prophylactic response
assessed by Alda Scale
in 70 bipolar patients
*** p<0.01
** p<0.05
* p=0.05
Depressive
- 0.233*
Cyclothymic
-0.256**
Hyperthymic
0.306***
Irritable
0.020
Anxious
-0.273**
Rybabowski et al, JAD, 2013; 145: 187-189
Genetic Influences on Response to
Mood Stabilizers in BP Disorder
- Recent studies: GWAS, ConLiGen, PGBD…
- Mostly on Lithium response
- Possible role of:
- Glutamatergic receptor AMPA (GRIA2) on
4q32
- Amiloride-sensitive cation channel (ACCN1)
on 17q12
- Sodium bicarbonate transporter (SLC4A10)
on 2q24
Rybakowski, CNS Drugs, 2013, 27: 165-73
Affective temperaments and
antidepressant response
• Lifetime history of AD response of 90 BP and 88
MDD
• Significant relationship between depressive anxious affective temperaments and absence of
antidepressant response.
• In BP: cyclothymic temperament (p<0.01) and
hyperthymic temperament (p<0.05) were
associated with antidepressant-associated mania.
• In MDD: Hyperthymic temperament was
associated with complete antidepressant
responses
De Aguiar Ferreira A et al. J Affect Disord. 2014 Feb;155:138-41
Activation Syndrom linked with
Antidepressants



Activation syndrome (AS) = cluster of symptoms
listed by the US FAD as possible suicidality
precursor during antidepressant treatment.
AS Rate = 52.2% of BP-II/BP-NOS vs 13.5% of
MDD, (p<0.01).
Factors linked with AS (Univariate analysis):

BP-II/BP-NOS diagnosis

Cyclothymic temperament

Early age at onset of first MDE

Psychiatric comorbidities

Depressive mixed state (DMX)
Takeshima & Oka, J Affect Disord. 2013 Oct;151(1):196-202.
Beyond Mania and DSMs:
Spectrum of Temperamental Bipolarity
MDE + Anxious /
Depressive
Temperament
(BP-III)
MDE +
Hyperthymic
Temperament
(BP-IV)
EDM +
Cyclothymic/Irritable
Temperament (BP-II1/2)
MoodStabilizer
Clinical predictors
Temperamental predictors
Lithium
Episodic course (free
intervals)
Euphoric hypomania
MDI sequence
Absence of rapid cycling
Family history of BP
- Hyperthymic dominant
traits
- High affective intensity
Valproate
Divalproate
Valpromide
Mixed hypomania
Rapid cycling
Anxious comorbidity
Substance abuse
Migraine
- Complex instable traits
(Cyclo – Anx – Irrit)
- High mood reactivity
- Borderline traits
Dominant depressive
recurrence
High mood lability and
instability
DMI sequence
- Depressive dominant
traits
- Borderline traits
- High emotional reactivity
and instability (ultra- rapid
switching)
Lamotrigine
Hantouche, Tempéraments Affectifs, J Lyon, Mars 2014
The most important point for
successful treatment of BP Disorder
• NOT: What is the next drug to add?
• BUT: What’s wrong with the patient? Patient’s
clinical profile? Primacy of Hypomania?
Dominant basic temperament
(stable/unstable)? Selective emotional
dimensions (stability, intensity, reactivity)?
Adapted from Grof, IRBD Meeting, Nice 2012
Temperament-based Management
of Bipolar Spectrum
- Innovative temperament-based classifications of
mood disorders
- Emerging clinical management strategies
- Optimal selective psychopharmacology
- Adapted psycho-education
- Focused psychotherapy on temperament
and lifestyles
- Improving acceptance - healing process
E Hantouche, Pan Arab Conference, Beirut, Nov 2014.
Regression analysis of relationships between specific
PTGI items and BRQ : Only one item
“I know better that I can handle my difficulties”
was a unique associate
Importance of confidence in one’s own resources in
recovery process
Temperament
Targets for Drug
Therapy
Targets for
Psychotherapy
Hyperthymic
Euphoric (hypo)mania
Affect Intensity
Substance abuse
Lifestyle linked with affect
intensity
Separation anxiety
Black/White
Depressive
Dominant depressive
recurrence
Mixed hypomania
Anxious comorbidity
Mood reactivity
Neuroticism
Focus on negative
Low self-esteem
Cyclothymic /
Irritable
High mood lability and
instability
Impulse control
disorders
Anxious comorbidity
Borderline traits
High emotional reactivity
Anger management
Sensitivity to rejection
Self-discipline
Self-sacrifice
Hantouche, Tempéraments Affectifs, J Lyon, Mars 2014
Tentative data suggests that bipolar patients who exhibit
more pronounced disturbance in positive emotion may
face a worse prognosis.
Philosophy
of Hippocratic Medicine
– Nature (temperament) is the
doctor’s friend
– The doctor is the handmaiden to
Nature
– Nature heals, the doctor assists
and facilitates the Nature’s work