JC Bisserbe April 2008 Mood disorders Frequent disorders, potentially lethal (up to 15% of suicide)...

JC Bisserbe April 2008

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

Mood Syndromes

Major depressive episode (and minor) Manic episode (hypomanic) Mixed episode


DSM IV classification of Mood Disorders

Adjustment disorder with depressive Mood

Mood Disorders

MDD

Dysthymia DDNOS

Unipolar Depressive Disorders

Bipolar 1 Bipolar 2

Cyclothymia

Bipolar Disorders

BDNOS

--Mood Disorder Due to a general medical condition

-Substance-Induced

Mood Disorder


Mood Disorders

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

Mood disorders prevalence

• 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



• 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



• Significant distress and/or impairment

• Substance/treatment or physical illness causation

• Bereavement (duration)


Depressive episode

• Specific features : melancolic, psychotic, catatonic, atypical, post-partum, seasonal pattern……


Depressive episode and et unipolar depressive disorder

• 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


Dysthymia (1)

• 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 :

– 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


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


Dysthymia (3)

• Early progressive onset inchildhood or adolescence

• Chronic course• Often diagnosed post-hoc when subject is

depressed (double depression) • Prevalence 3-7 % ?• Treatment as depression


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…)


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


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


Manic episode specific features

• With psychotic features : delusion (grandiose, persecution) hallucination

• Antidepressant induced “bipolar diathesis”


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


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


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

Bipolar disorder type I (1)Epidemiology and age of onset

• 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


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


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


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%)


Bipolar disorder type II (3)Comorbities

• Alcohol (50%), drugs

• Anxiety disorders (50%)

• Eating disorders

• Personality disorder (1/3)


Bipolar disorder spectrum

• Cyclothymia

• Bipolar III : antidepressant induced– Same outcome

• Heterogeneous disorder


Bipolar disorder type I and II Diagnostic issues

• Underdiagnosed/late diagnosis : consequences

• Bipolar and schizophrenia and schizoaffective disorders


Vincent van Gogh Virginia Woolf Sylvia PlathMozart ?Charles QuintBen StillerLarry FlyntLouis AlthusserVivien Leigh Edgar Allen Poe Robert SchumanPhil Spector Buzz Aldrin ?Ned Beatty Graham GreeneIlie NastasePierre PeladeauAugust StrindbergTom WaitsCharles BeaudelaireLudwig BoltzmannLudwig Van BeethovenLeon TolstoiGustav Mahler

Isaac Newton Jeff BuckleyWinston Churchill Kurt CobainOtto KlempererJack LondonRay 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 TwainBrian WilsonJean-Claude Van Damme

Famous bipolar Kay Redfield Jamison's Touched With Fire, National Alliance Mental Illness


Schematic time course of a depressive episode treatment

Relapse prevention Recurrence prevention


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, 8-12 weeks for adolescent and elderly


Bipolar disorders:treatment principles

• Acute episodes : mood stabilizer (anticonvulsant, lithium) plus adjunct treatment– Depression : lamotrigine, valproate, lithium,

antidepressants ?– Mania: lithium, valproate, antipsychotic

(benzodiazepine)


Bipolar disorderRelapse 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 ++++


Treatment algorithms

• CANMAT, TIMA …

• Consensus, some evidence

• According to – bipolar type – Index episode– Ratio mania/depression– Comorbid conditions– Other treatments


:

TIMA hypomanic-manic-mixed algorithm

• 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


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.


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.


Aetiology of Bipolar disorder

• Most likely complex

• Interaction of multiple genes with the environment


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)


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)


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 Mood disorders Frequent disorders, potentially lethal (up to 15% of suicide)...

Documents

Transcript of JC Bisserbe April 2008 Mood disorders Frequent disorders, potentially lethal (up to 15% of suicide)...