Download Dr. J. C. Bisserbe

Mood disorders
• Frequent disorders, potentially lethal (up to 15%
of suicide)
• High comorbidity with somatic diseases
(cardiovascular ++)
• Individual, familial, social impact
• Social cost*
• Can be treated
*WHO ranked depression as one of the top four medical conditions with the greatest disease burden
worldwide, measured in disability-adjusted life years, which express year of life lost to premature
death and years lived with a disability of specific severity and duration. In 2020 depression will be
the second largest contributor of disease burden worldwide
JC Bisserbe April 2008
Mood Syndromes
 Major depressive episode (and minor)
 Manic episode (hypomanic)
 Mixed episode
DSM IV classification of Mood Disorders
Mood Disorders
--Mood Disorder Due to a
general medical condition
-Substance-Induced
Mood Disorder
Unipolar Depressive Disorders
MDD
Dysthymia
DDNOS
Bipolar Disorders
Bipolar 1 Bipolar 2
Cyclothymia
Adjustment disorder with depressive Mood
JC Bisserbe April 2008
BDNOS
Mood Disorders
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Bipolar disorders type I and II
Unipolar disorder single/recurrent
Dysthymia (chronic low mood)
Cyclothymia (chronic ups an downs)
Adjustment disorder with depressive mood
(stressor)
Chronic and recurrent course
JC Bisserbe April 2008
Mood disorders prevalence
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Epidemiologic Catchment Area Study
(ECA) National Comorbidity Survey
(NCS) Depression lifetime prevalence
20% females 10% males (point prevalence 5-10%)
Dysthymia 3-7% lifetime.
Bipolar I&II : 2-7% lifetime
Kessler et al The Epidemiology of Major Depressive Disorder Results
From the National Comorbidity Survey Replication (NCS-R)
JAMA. 2003;289:3095-3105.
Depressive episode (1)
• Depressive mood : feeling of sadness most of the
day nearly everyday (down, discouraged,
hopeless…)
• Diminished pleasure or interest : lack of
motivation, feeling like doing nothing, having no
feelings (direct or indirect evidence)
TWO WEEKS DURATION
JC Bisserbe April 2008
Depressive episode (2)
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Reduced/increased appetite, weight loss/gain
Insomnia/hypersomnia
Agitation/retardation
Fatigue loss of energy
Worthlessness/guilt
Cognitive symptoms :ability to think, indecisiveness
Suicidal ideation
TWO WEEKS DURATION
JC Bisserbe April 2008
Depressive episode (3)
• Significant distress and/or impairment
• Substance/treatment or physical illness
causation
• Bereavement (duration)
JC Bisserbe April 2008
Depressive episode
• Specific features : melancolic, psychotic,
catatonic, atypical, post-partum, seasonal
pattern……
JC Bisserbe April 2008
Depressive episode and et unipolar
depressive disorder
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4 to 9 month duration, 5-10% more than 5 years
2/3 complete remission (chronicity 5% after 5 years)
Age first episode 30-35 y *
Two females for a male (20%vs10%)
Relapse >50% if early treatment termination
Recurrence 50% after one episode, 90% after 3
episodes
Comorbidity : alcohol, anxiety disorders, physical
diseases (cardiovascular++)
*Age cohort effect
JC Bisserbe April 2008
Dysthymia (1)
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A. Depressive mood mosst of the daymore days
than not present for at leat 2 years reported by
the subject or observed by others
B. Presence when depressed of at least two of the
following :
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Loss of appetite or overeating
Insomnia or hypersomnia
Low energy or fatigue
Low self-esteem
Poor concentration or difficulties to make decison
Feelings of hopelessness
JC Bisserbe April 2008
Dysthymia (2)
• C. In the last two years the person has never
without the symptoms A and B
• D. No depressive episode in the first two years
of the disturbance
• No manic/hypomanic episode
JC Bisserbe April 2008
Dysthymia (3)
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Early progressive onset inchildhood or
adolescence
Chronic course
Often diagnosed post-hoc when subject is
depressed (double depression)
Prevalence 3-7 % ?
Treatment as depression
JC Bisserbe April 2008
Manic episode (1)
• Distinct period of abnormally and
persistently elevated, expansive or irritable
mood, lasting at least a week
• Marked impairment in occupational
functioning and/or social activity,
relationship with others (hospitalization,
police intervention…)
JC Bisserbe April 2008
Manic episode (2)
• Inflated self-esteem
• Decrease need for sleep with increased level of energy
• More talkative and interactive than usual or pressure to keep
talking (increased sociability)
• Flight of ideas, subjective feeling that thoughts are racing
• Distractibility
• Increase in goal-oriented activity or psychomotor agitation
(excessive planning, multiple activities)
• Excessive involvement in pleasurable activities (buying
sprees, foolish business, promiscuity…)
Present to a significant degree during the mood disturbance
JC Bisserbe April 2008
Manic episode
Onset course
• Early onset 20s (childhood, adolescence)
• Rapid installation in a few days often starting with
reduced (no) sleep
• Duration shorter than depression 2-4 months
• Rapid ending followed by depression (>50%)
• Post-partum
• Psychosocial stressors in preceding months
• Relapse/recurrence
JC Bisserbe April 2008
Manic episode specific features
• With psychotic features : delusion
(grandiose, persecution) hallucination
• Antidepressant induced “bipolar diathesis”
JC Bisserbe April 2008
Hypomanic episode
• Similar to Manic episode
– with lower intensity
– Less impairing and with limited functional
impact observable by others
– Shorter duration (4days)
– No psychotic features
JC Bisserbe April 2008
Depressive episode in bipolar disorders
• Atypical features : increased sleep and
appetite, irritability, fatigue, reactive mood
• Psychomotor retardation (blunted affect)
• Melancholic and psychotic features
• Seasonal
• (poor response to antidepressant)
• Earlier onset compared to unipolar
JC Bisserbe April 2008
Bipolar type I
• At least one Manic episode or Mixed
episode
Bipolar type II
• At least one hypomanic episode and a one
(or more) depressive episode
JC Bisserbe April 2008
Bipolar disorder type I (1)
Epidemiology and age of onset
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Prevalence 1 -2%
Equal in men and women
Early onset 20s (childhood, adolescence)
10-15% adolescent depression will evolve toward
bipolar disorder
Bipolar disorder type I (2)
Course and outcome
• Recurring course 90 % of patient with one episode will
have recurrence (mostly more than 3 episodes)
• Residual symptoms (mood fluctuation)
• Cognitive and thought disorders
• Suicidal risk (10-15%)
• Chronic impairment in 15-30% of bipolar
• Rapid cycling
• Role of treatment
• Better outcome than schizophrenia
JC Bisserbe April 2008
Bipolar disorder type I (3)
Comorbidities
• Alcohol and drug abuse (cocaine, marijuana) several time
higher than the general population (up to 50%)
• Anxiety disorders (Panic disorders, OCD, social phobia)
• Somatic comorbidities : cardiovascular, metabolic
• Forensic and antisocial behaviour
JC Bisserbe April 2008
Bipolar disorder type II (1)
Epidemiology and age of onset
• Prevalence 2-5% controversial
– Poorly recognized (50%)
– Clinical boundaries
– Bipolar spectrum
• More frequent in women ?
• Onset in late adolescence with depressive
symptoms and mild mood swings with
progressive increase (later than BPI)
• Early onset= severity
JC Bisserbe April 2008
Bipolar disorder type II (2)
Course and outcome
• Chronic course
• Depressed symptoms present up to 50% of the time
manic symptoms present about 2% of the time
• Presence of mixed state (hypomanic and depressed
symptoms)
• Rapid cycling
• Suicide risk (Mixed state)
• More recurrent than BPI ?
• Evolution to BPI (15%)
JC Bisserbe April 2008
Bipolar disorder type II (3)
Comorbities
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Alcohol (50%), drugs
Anxiety disorders (50%)
Eating disorders
Personality disorder (1/3)
JC Bisserbe April 2008
Bipolar disorder spectrum
• Cyclothymia
• Bipolar III : antidepressant induced
– Same outcome
• Heterogeneous disorder
JC Bisserbe April 2008
Bipolar disorder type I and II
Diagnostic issues
• Underdiagnosed/late diagnosis :
consequences
• Bipolar and schizophrenia and
schizoaffective disorders
JC Bisserbe April 2008
Famous bipolar
Kay Redfield Jamison's Touched With Fire, National Alliance Mental Illness
Vincent van Gogh
Virginia Woolf
Sylvia Plath
Mozart ?
Charles Quint
Ben Stiller
Larry Flynt
Louis Althusser
Vivien Leigh
Edgar Allen Poe
Robert Schuman
Phil Spector
Buzz Aldrin ?
Ned Beatty
Graham Greene
Ilie Nastase
Pierre Peladeau
August Strindberg
Tom Waits
Charles Beaudelaire
Ludwig Boltzmann
Ludwig Van Beethoven
Leon Tolstoi
Gustav Mahler
Isaac Newton
Jeff Buckley
Winston Churchill
Kurt Cobain
Otto Klemperer
Jack London
Ray Davies
Charles Dickens
DMX
Marilyn Monroe ?
Francis Scott Key Fitzgerald
Ernest Miller Hemingway
Hermann Hesse
Jimi Hendrix ?
Patrick Joseph Kennedy
Abraham Lincoln
Charles Mingus
Edvard Munch
Ozzy Osbourne
Robert Louis Stevenson
Mark Twain
Brian Wilson
Jean-Claude Van Damme
JC Bisserbe April 2008
Schematic time course of a depressive episode
treatment
Relapse prevention Recurrence prevention
JC Bisserbe April 2008
Unipolar depression treatment
(CANMAT guidelines)
1. SSRI or psychotherpy (CBT,IPT)
2. Other SSRI ou antidepressant of another group
3. Other antidepressant class or augmentation
(lithium, thyroid hormones, AD association….)
4. MAOI
5. Therapeutic trial at least 6-8 weeks for adults, 812 weeks for adolescent and elderly
JC Bisserbe April 2008
Bipolar disorders:
treatment principles
• Acute episodes : mood stabilizer (anticonvulsant,
lithium) plus adjunct treatment
– Depression : lamotrigine, valproate, lithium,
antidepressants ?
– Mania: lithium, valproate, antipsychotic
(benzodiazepine)
JC Bisserbe April 2008
Bipolar disorder
Relapse and recurrence prevention
– Mood stabilizers, Antidepressants , Atypical
antipsychotic
– Psychoeducation : partnership, insight,
treatment adherence, early signs of
relapse/recurrence, coping strategies
– Specific treatment programs: follow-up,
cognitive behaviour therapies
Lithium ++++
JC Bisserbe April 2008
Treatment algorithms
• CANMAT, TIMA …
• Consensus, some evidence
• According to
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bipolar type
Index episode
Ratio mania/depression
Comorbid conditions
Other treatments
JC Bisserbe April 2008
TIMA hypomanic-manic-mixed algorithm
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first stage monotherapy
• euphoria includes lithium, valproate, or any one of several
atypical antipsychotics
• mixed states all are recommended except lithium.
• stage 2 if no response or an inadequate response several of
the two drugs recommended in stage 1( except that atypical
antipsychotics are not to be used concurrently, and aripiprazole
and clozapine are not recommended)
• stage 3, the anticonvulsants carbamazepine, oxcarbazepine,
and topiramate are added to the choices for two-drug
treatment, and aripiprazole is added to the available
antipsychotics. Again, no two atypical antipsychotics are to be
used concurrently.
• stage 4, electroconvulsive therapy is an option, as is the
addition of clozapine or a three-drug regimen consisting of
lithium, an anticonvulsant, and an antipsychotic
JC Bisserbe April 2008
The TIMA depressive algorithm(1)
• Stage 1, determine whether the patient is taking lithium or any
other antimanic, as well as whether the patient has a history of
recent or severe mania.
- If taking lithium, the dose should be increased to 0.8 mEq / L;
- if taking another antimanic, it should be continued, with
lamotrigine added.
- If not receiving an antimanic and having a history of recent or
severe mania: lamotrigine or another antimanic;
- if no such history is present and the patient is not taking a
current antimanic, lamotrigine should be initiated.
• Stage 2, quetiapine or the combination of olanzapine and
fluoxetine added to the stage 1 regimen.
JC Bisserbe April 2008
The TIMA depressive algorithm(2)
• Stage 3, a multidrugs regimen is recommended :
- lithium, lamotrigine, quetiapine,
- combined olanzapine and fluoxetine.
• Stage 4,
- all of the stage 3 drugs are available as well as valproate;
- a combination of carbamazepine and SSRI, buproprion, or
venlafaxine;
- electroconvulsive therapy.
• Stage 5, consider monoamine oxidase inhibitors, tricyclic
antidepressants, pramipexole, other atypical antipsychotics
beyond quetiapine and olanzapine, other combinations of drugs
used in earlier stages, or inositol, stimulants, or supplemental
thyroid.
JC Bisserbe April 2008
Aetiology of Bipolar disorder
• Most likely complex
• Interaction of multiple genes with the
environment
JC Bisserbe April 2008
Genetic of bipolar disorder
• Relative risk to develop Bipolar disorder is 5-10% in first
degree relative (40-70% in monozygotic twins) and 5-1.5%
in the general population.
• Increase risk to develop unipolar diorder in children of
bipolar patient as well as increase to develop bipolar
disorder in children of unipolar
• Bipolar disorder is heritable but mechanism of transmission
is unknown
• Multiple candidate genes on various chromosomes
• Genetic of drug response (lithium)
JC Bisserbe April 2008
Neuroanatomy of bipolar disorder
• Neuroanatomical studies :
– limbic structures (amygdala, hippocampus*) and the
thalamus role in mood and cognition
– Cingulate and prefrontal cortex
• Functional studies
– More activation in emotional brain (hippocampus,
amygdala, prefrontal cortex)
– Recruitment of subcortical region for emotional
evaluation (caudate, thalamus,amygdala)
JC Bisserbe April 2008
Neurochemistry of bipolar disorder
• Serotonin system :involved in the
pathophysiology of depression
– 5HT2A , 5HT1A receptors
• Dopaminergic system : dopamine synthesis
increase in mania
• Intracellular signaling
• Neurotrophic factors and cell atrophy and
death
JC Bisserbe April 2008