bipolar disorder
DESCRIPTION
Mood Disorders (18.19-2-2010)TRANSCRIPT
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ByDr. Maged Al Adrousy Lecturer of psychiatry- Cairo university
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introduction
Bipolar disorder is an episodic, potentially life-long, disabling disorder that can be difficult to diagnose.
known as Manic Depression, Results in pathological mood swings from mania to depression, These mood swings occur spontaneously.
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Euthymia
Mania
Depression
Euthymia
Mania
Depression
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History Bipolar Disorder
200 CE First reports 1654 Jean Pierre Falret
“folie circulaire" (circular insanity) Familial illness
1913 Emil Kraepelin Manic - Depressive
1930’s ECT first used 1949 Lithium first used 1950 Chlorpromazine first used 1952 Genetic link recognized 1980 Bipolar Disorder term adopted 1995 Depakote approved for BP 2003 First atypical approved for BP
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Types of Mood Disorders
DSM IV Major Depressive
Disorder Dysthymic Disorder Bipolar Disorder Type I Bipolar Disorder Type II Cyclothymic Disorder NOS
Mixed Phase Rapid Cyclers Bipolar Spectrum (BPS)
86%
2%
2%
10%
MDD
BP I
BP II
NOS
50%
2%15%
33% MDD
BP I
BP II
BPS
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Bipolar disorder is a cyclical mood disorder Abnormally elevated mood or irritability
alternates with depressed moodbipolar I – at least one manic or mixed episodebipolar II – at least one major depressive episode
and at least one hypomanic episodeCyclothymia = hypomania with “minor” depression“Bipolar spectrum” = Depression + other
complexities Bipolar NOS or Mood DO NOS
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Structure of a Recurrent Illness
Underlying illness
Precipitant
Episode
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Spectrum of Illness Course
Purely episodic course:-interepisode stability-no mixed states-infrequent episodes-good recovery-low incidence of complications
Radical mood instability:-’interepisode’ instability -mixed states-frequent episodes-incomplete recovery-high incidence of complications-early onset-stronger genetic loading?
Episodic Unstable
Course of illness dictates response strategies for the acute episode
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DIAGNOSTIC CRITERIA FOR MANIC EPISODES
THREE TO FOUR OF THE FOLLOWING CRITERIA ARE REQUIRED DURING THE ELEVATED MOOD PERIOD
Highly inflated or grandiose self-esteem
Decreased need for sleep, or rested after only a few hours of sleep
Pressured speech
Racing thoughts and flight of ideas
Easy distractibility, failure to keep attention
Increased goal-directed activity
High excess involvement in pleasurable activities (sex, travel, spending money)General criteria for a manic episode require a period of
elevated, expansive, or irritable mood that lasts 1 week or requires hospitalization. A general medical condition and substance abuse must be ruled out before these symptoms are considered mania.
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Manic Episode: Differential Diagnoses
Differential diagnosis Consider if . . . Mood disorder due Mood disorder due to a general medical to a general medical conditioncondition
Substance-inducedSubstance-inducedmood disordermood disorder
Hypomanic episodeHypomanic episode
Mixed episodeMixed episode
Major medical condition Major medical condition present present
First episode at >50 years of First episode at >50 years of ageage
Symptoms in context of Symptoms in context of intoxicationintoxicationor withdrawalor withdrawal
History of treatment for History of treatment for depressiondepression
Mood disturbance not severeMood disturbance not severeenough to require enough to require hospitalizationhospitalizationor impair functioningor impair functioning
Manic episode and MDE in 1 Manic episode and MDE in 1 weekweek
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Manic Episode: Differential Diagnoses (cont.)
AD/HDAD/HD Early childhood mood disturbance Early childhood mood disturbance onset onset
Chronic rather than episodic courseChronic rather than episodic course
No clear onsets and offsets No clear onsets and offsets
No abnormally elevated moodNo abnormally elevated mood
No psychotic features No psychotic features
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). 4th ed. 1994.
Differential diagnosis Consider if . . .
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Depressed mood and/or loss of interest
or pleasure 2 weeks duration Associated symptoms
Physical: insomnia/hypersomnia, appetite/weight change, decreased energy, psychomotor change
Psychological: feelings of guilt or worthlessness, poor concentration/indecisiveness, thoughts of death/suicidal intentions (SI)
Major Depressive Episode: DSM-IV Criteria
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…and 4 of the following symptoms
Physical Sleep disorder Appetite change Fatigue Psychomotor
retardation
Psychological Low self
esteem/guilt Poor
concentration/indecisiveness
Thoughts of death/SI
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Mixed Episode: Diagnostic Criteria Criteria met for both manic episode
+ MDE for 1 week Symptoms
Are sufficient to impair functioning or
Necessitate hospitalization or
Are accompanied by psychotic features
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Epidemiology
Peak age of onset: adolescence through early 20s Onset of first manic episode after age 40 years is
“red flag” to consider substance use or general
medical condition
Lifetime suicide rates range from 10% to 15%
Seasonal variation Depression more common in spring and autumn Mania more common in summer
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Characteristics BPD I BPD II
Prevalence 1.6% 0.5%
Ethnic/racial differential None None
Gender differential M = F F›M (?)
Bipolar Disorders: Epidemiology
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Characteristics BPD I BPD II
Bipolar Disorders: Epidemiology
Hypomanic episodes in BPD II immediately precede or follow MDEs in 60% to 70% of cases
First-degree relatives may have increased rates of BPD I, BPD II, and MDD
Recurrent in >90% of cases
First-degree relatives have increased rates of BPD I, BPD II, and MDD
Course
Familial pattern
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Diagnostic Dilemmas: Unipolar Versus Bipolar
No evidence of hypomania, cyclothymia, hyperthymic personality, or family history of BPD1 manic episodeRecurrent major depression with hypomania and/or cyclothymic temperament
Recurrent major depression without spontaneous hypomania but often with hyperthymic temperament and/or family history of BPD
Unipolar
BPD IBPD II
BPD NOS
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Bipolar vs unipolar
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BD II
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CYCLOTHYMIC DISORDER
Cyclothymic disorder is a recurrent, chronic, mild form of bipolar disorder in which mood typically oscillates between hypomania and dysthymia.
If a manic episode or depressive episode is experienced, cyclothymic disorder is not diagnosed. http://www.allaboutdepression.com/cyclothymia/
images/graphic2.gif
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CYCLOTHYMIC DISORDER
EPIDEMIOLOGY ETIOLOGY
The lifetime prevalence of cyclothymic disorder is 0.4%
to 1%.
Genetic and familial studies reveal an association with
other mood disorders
The rate appears equal in men and women, although women are usually more likely to seek treatment
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CLINICAL MANIFESTATIONS OF CYCLOTHYMIC DISORDER Cyclothymic disorder is a milder form of
bipolar disorder consisting of recurrent mood disturbances between hypomania and dysthymic mood.
A single episode of hypomania is sufficient enough to diagnose cyclothymic disorder, although most individuals also have dysthymic periods.
Cyclothymic disorder is never diagnosed when there is a history of mania, major depressive episode, or mixed episode.
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Etiology
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Heritability
Evidence for heritability is much stronger for bipolar than for unipolar disorders
Specific genetic association has not been consistently replicated
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EVIDENCE FOR HERITABILITY OF BIPOLAR DISORDER
Family Studies- First degree relatives are 8 to 18 times more likely to have Bipolar I
2 to 10 times to have MDD.
Risk is 25% if one parent has illness, and 50% to 75% with both parents affected
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FAMILY STUDIES
The majority of individuals with bipolar disorder have a positive family history of some type of mood disorder
About 50% of all bipolar I patients have at least one parent with a mood disorder
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ADOPTION STUDIES
Prevalence of bipolar disorder in adopted away offspring corresponds to rates in biological, but not adoptive relatives
Twin Studies- Concordance rate in MZ twins is 33 to 90%, in DZ is 5 to 25%
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Genetic Polymorphism A functional polymorphism is a genetic
variant that appears in at least 1% of a population and alters the biological functioning of the individual
Some types of polymorphisms in Mood Disorders Serotonin transporter Serotonin 2A receptor MTHF reductase Catachol -o- methyl tranferase (COMT) Tyrosine hydroxylase Cytochrome P450 metabolism of medications
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Biological factors
Dysregulation in levels catecholamines (++ levels of dopamine and norepinephrine).
-- levels of serotonoine ?? Neuroendocrinal factors:• HPA axis (cortisol hypersecreation) may
affect BDNF.• Throid dysfucntion. EEG changes (kindling model) Degenerative structural brain changes.
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Psychosocial factors
Life time events. Behavioral models . Psychological theories.
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Impact of BD
Higher rates of mortality from other medical conditions
Increased substance abuse risk Lifetime suicide attempt risk (.02% in general
populatio Bipolar Disorder Type I – 17% Bipolar Disorder Type II – 24% 90% of completed suicides can be traced
back to a Mood Disorder High rates of cognitve defeicets affecting
Working memory Sustained attention, Abstract reasoning, Visuomotor skills, Verbal memory, Verbal fluency, Cognitive flexibility
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Management
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A- psychopharmacology
Mood stabilizers Atypical antipsychotics. Benzodiazepines. Channel blockers. Others Combination therapy is more
effective than monotherapy
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Mood stabilizers
Lithium Conventional anti-epileptics as
carbamazepine and Na valproate. New anti-epileptics lamotrigene
gababentine, and topiramate
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What Exactly Is a Mood Stabilizer?
• Some authorities suggest 2 out of 3 of the following properties:
– Antimanic, antidepressive, prophylactic
• Other experts are more stringent—requiring:
– Treatment of acute mania,
– Treatment of acute depression, AND
– Prevention of recurrent mania and depression
– Dosen’t ppt mania or depression.
• Lithium remains the gold standard
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Lithium
Widely recommended treatment for Bipolar Disorder
60-80% success in reducing acute manic and hypomanic states
However… issues in non-compliance to take medication, side effects, and relapse rate with its use are being examined in terms of being the best option
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Pharmacokinetics:
Peak blood levels reached in 3 hrs, fully absorbed in 8 hrs
Absorbed rapidly and completely orally Efficacy correlates with blood levels Crosses blood-brain barrier slowly and
incompletely Usually taken as a single daily dose
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Kinetics Cont.
Approx. 2 wks to reach a steady state within the body
½ of oral dose excreted in 18-24 hrs,rest within 1-2 wks
Recommended 0.8-1.2 mEq/L, optimum would be 0.6-0.8 mEq/L, with 2 mEq/L displaying toxicity .
Monovalent ion not metabolized in liver, excreted by the kidney.
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Pharmacodynamics
No psychotropic effect on non-Bipolars Affects nerve membranes, multiple
receptor systems and intracellular 2nd messenger impulse transduction systems.
Interacts with serotonin Potential to regulate CNS gene
expression, stabilizing neurons w/ associated multiple gene expression change.
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How does a simple ion do all of this?
Even as a simple ion, it has complex effects on multiple transmitter systems and mood stabilizing attributes
This is due to a latter effect reducing a neuron’s response to synaptic input, and therefore stabilizing the membrane
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Side Effects and Toxicity
Relate to plasma concentration levels, so constant monitoring is key
Higher concentrations ( 1.0 mEq/L and up produce bothersome effects, higher than 2 mEq/L can be serious or fatal
Symptoms can be neurological, gastrointestinal, enlarged thyroid, rash, weight gain, memory difficulty, kidney disfunction, cardiovascular
Not advised to take during pregnancy, affects fetal heart development
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Side effects of Li
1. GIT symptoms (diarrhea intially)2. Hypokalaemia…….cardiotoxic.3. Polyuria and D.insipius (ADH).4. Tremors.5. Epileptogenic.6. Teratogenic.7. hypothyroidism8. Li toxicity may occure (ttt?)
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Na valproate
Tab 200mg and 500 mg Dose 50-150 mg% Best for rapid-cycling and acute-mania Actions: through GABA potentiation,
Ca channel blockade, Na channel blockade, glutamat antagonist.
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Side effects1.Hepatotoxic.2.Wt gain3.Hair loss.4.GIT symptoms.5.Tremors and sedation6.Neural tube defects
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carbamazepine Tab 200mg 400 mg Dose 5-15 µg/L Action similar to valproate. Superior to lithium for rapid-cycling,
regarded as a second-line treatment for mania
Correlation between therapeutic and plasma levels (estimated between 5-10 Mg/L)
Side effects:1. Agranulocytosis2. Skin reaction3. Teratogenic4. Liver enzyme induction
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Gabapentin
Primarily an anti-convulsant, yet also “off label,” or without FDA approval for treatment of Bipolar and many other anxiety, behavioral and substance abuse problems, possibly pain disorders
GABA analogue not bound to plasma proteins, not
metabolized, few drug interactions Half-Life is 5-7 hours Side Effects include
sleepiness,dizziness,ataxia and double vision
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Lamotrigine
Reported effective with Bipolar, Borderline Personality, Schizoaffective, Post-Traumatic Stress Disorders
98% of administered drug reaches plasma
Half-Life is 26 hrs. Inhibits neuronal excitability and
modifies synaptic plasticity Side Effects may include dizziness,
tremor, headache, nausea, and rash
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Topiramate and Tiagabine
Two newer anti-convulsants that have potential for use in the treatment of Bipolar disorder
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Anticonvulsants: Efficacy in BD
Probably effective:
Lamotrigine, CBZ, oxycarbazepine, valproate
Possibly effective:
Gabapentin, zonisamide, phenytoin, levetiracetam
Ineffective/problematic:
Topiramate, tiagabine, vigabatrin
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Calcium Channel Blockers Modulate transmitter release &
plasticity
Most not consistently effective, possibly due to inconsistent uptake into brain
Nimodipine reported effective in rapid-cycling, including refractory & ultra-rapid
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Atypical Anti-psychotics
Risperidone seems more anti-depressant than anti-psychotic
Clozapine is effective, yet not readily used due to potential serious side effects
Olanzapine is approved for short-term use in acute mania
Quatiapine is now approved as a broad spectrum medication in BD esp (Bipolar depression).
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Acetylcholinesterase Inhibitors
Potentiating the action of acetylcholine may exert relief from mania
This potentiation is the result of inhibiting the enzyme acetylcholine esterase
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Omega-3 Fatty Acids
Obtained from plant or marine sources
Known to dampen neuronal signaling transduction systems in a variety of cell systems
Being investigated as a treatment for Bipolar Disorder
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Three Phases of Treatment
0-2 months 2-12 months IndefiniteSymptomatic Functional Stability/adaptive
Episode Continuation Maintenance
Each phase has specific goalsEach phase has specific pharmacological and nonpharmacological rxTreatment must be harmonized across phases
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Nonpharmacologic Treatments ECT
Reports of effectiveness in mania, depression, & refractory mixed states
Bilateral generally more effective Continuation ECT may prolong recovery;
maintenance? Transcranial magnetic stimulation Psychotherapy : May include cognitive
behavioral, psychodynamically oriented, family, couples, interpersonal, and self-help group therapies
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Thank you