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Dr.G.RAMANUJAM MD
Associate Professor
Tirunelveli Medical College
DISCRETE
VS
CONTINUOUS
 CATEGORICAL
 WATER TIGHT
 NO OVERLAPS
 DISCRETE
 PRESENCE OR
ABSCENCE
 DIMENSIONAL
 SINGLE OR MULTIPLE
FACTORS
 PRESENT IN ALL
 CLASSIFIED
ACCORDING TO
DEGREE
 DENOTES TWO
EXTREMES
 EQUATES WITH MANIA
THE HIGH
 PATIENT DENIES BEING
MANIAC
 ACCEPTS DEPRESSION
 EITHER MANIA OR
DEPRESSION
 ITALIAN PSYCHIATRIST
 WORKED INFLORENCE
 DESCRIBED
CLASSIFICATION
 MANIA,
MELANCHOLIA,DEMEN
TIA
 German psychiatrist
 Director of Sachsenberg mental hospital
 Dysthymia mutabilis
 Mixture of Dysthyma atra (Black depression)
and Dysthyma candida (low-level mania).
 Saltpetriere Hospital
Paris
 La folie circulaire
1951
 Alternating Mania and
Melancholia
 Different from Mania
and melancholia
 French Psychiatrist
 Collegue at
Saltpetriete
 Claimed that he was
the first the describe
cyclic illness
 Tussle with Falret
 GERMAN PSYCHATRIST
 INTRODUCED THE
TERM CYCLOTHYMIA
 ASSOCIATE HECKER
 CATATONIA
 HEBEPHRENIA
 GERMAN
PSYCHIATRIST
 GREAT CLASSIFIER
 MANIC DEPRESSIVE
PSYCHOSIS
 DEMENTIA PRECOX
 UNITARY CONCEPT
 GERMAN
 STUDENT OF
WERNICKE
 COINED BIPOLAR
 AND UNIPOLAR
 ASSOCIATE OF KLIEST
 MULTIPLE SUBTYPES
 CYCLOID PSYCHOSIS
 POPULARIZED
UNIPOLAR BIPOLAR
Poles what is reality
Eca survey
 Incidence of Bipolar disorder is
1.2% (1988)
 Ratio of Unipolar : Bipolar is
4:1
RECENT
 6.4% (Judd &Akiskal 2003)
% among psy patients
 One third of Depressed outpatients (Cassano 1989)
 45% of Depressed Outpatients (Benazzi 1997)
 60% Depressed Ghaemi
 BIPOLAR ILLNESS IS COMMONLY MISSED
 48% INITIALDIAGNOSISWAS MISSED
 54% DIAGNOSED AS UNIPOLAR DEP
 34%AS BIPOLAR
 AVERAGE ITTOOK 8YRSTO DIAGNOSEAS
BPD
FOLLOW UP OF PREPUBRTAL AND
ADOLESCENT DEPRESSION
HOW TO APPROACH BIPOLAR
BIPOLAR Vs UNIPOLAR SAME OR DIFF
 CLINICALLY DIFFERENT?
 GENETICALLY DIFFERENT?
 NEUROBOLOGICALLY DIFFERENT?
 TREATMENT ?
IF BOTH BD &UD ARE DIFFERENT
CLINICAL DIFFERENCE BETWEEN BD
AND UD
BIPOLAR NOT NECESSARILY TWO
OPPOSITE ENDS
AGITATED DEPRESSION
 RACING THOUGHTS
 PSYCHOMOTOR AGITATION
 IRRITABILITY
 STRONG BIPOLAR FAMILY HISTORY
 ANTI DEPRESSANT INDUCED DESTABILIZATION
 Akiskal Benazzi 2004
BIPOLAR DISORDER
CHANGING PARADIGMS
AKISKAL
BIPOLAR DISORDER V
DEPRESSION WITH MIXED HYPOMANIA
BIPOLAR DISORDER VI
BIPOLAR IN THE SETTING OF DEMENTIA
BIPOLARITY INDEX
DSM V
 Better than DSM IV
 MANIC, HYPOMANIC, DEPRESSVE EPISODE
 No MIXED episode
 NOS omitted
 BIPOLAR I, II CYCLOTHYMIA, SUBSTANCE, OTHER
MEDICAL CAUSES
MIXED
 MIXED FEAUTURES IS A SPECIFIER
 DEPRESSIVE EPISODE WITH MIXED FEATURES-
Agitated Depression
 MANIC OR HYPOMANC EPISODE WITH MIXED
FEATURES- Dysphoric Mania
OTHER SPECIFIER
 ANXIOUS DISTRESS
 CATATONIC
 MIXED
 SEASONAL
 MOOD CONGRUENT PSYCHOTIC
 MOOD INCONGRUENT PSYCHOTIC
 ATYPICAL
 POST PARTUM ONSET

OTHER SPECIFIED BIPOLAR AND
RELATED DISORDER
 SHORT DURATION HYPOMANIC EPISODES AND
MAJOR DEPRESSVE EPISODES
 HYPOMANIC EPISODES WITH INSUFFECIENT
SYMPTOMS AND MAJOR DEPRESSIVE DISORDER
 HYPOMANIC EPISODE WITHOUT PRIOR
DEPRESSIVE EPISODE
 SHORT DURATION CYCLOTHYMIA
Neurobiology OF MANIA AND BIPOLAR
DISORDER*
Ambiguous till date
Biogenic amine neurotransmitters:
Noradrenergic system:
NE turnover increase in the cortical and thalamic areas of BD subjects where
decrease in depression
• Serotogenic system:
Reduced 5-hydroxytryptamine (5- HT)1A receptor binding potential in raphe
and hippocampus- amygdala of brain in depressed patients
Dopaminergic system
• DA agonists are effective antidepressants and are able to precipitate
mania.
• D2 receptor found in caudate, putamen, nucleus accumbens, cerebral
cortex and hypothalmus is negativly coupled to adenylyl cyclase. Older
antipsychotics act through blockage of D2 receptors , which eventualy
result in extrpyramidal system (muscle rigidty , involuntry movement,
pseudoparkinsonism)
 Worldwide disorder
 Age at onset : Adult , Children & Adolescent
 Among the top 10 of GBD ( Global Burden of diseases)
 Fifth / Sixth amongst reported disability
 An under diagnosed and under treated disorder
Bauer in, eds Tasman et al 2003
Bipolar depression Disease Burden
 Patients with onset in mid to late 20’s effectively
lose 9 years of life, 12 years of normal health
and 14 years of normal activity
 Increase likelihood of divorce by 3 X
Montgomery SA, Cassano GB, Management of bipolar disorder, 1996 , p5
Bipolar depression Disease Burden
 Years lived with disorder :
Depression > Mania / Hypomania
Comorbidity:
- Anxiety disorders : 52%
( Panic, GAD, Social Phobia )
- Substance abuse disorder : 39%
 Suicide
- 10% to 19-20% , 15 -30 times > general population
- At least 25% will attempt suicide
- 80% suicide attempts / completed suicide occur in depressed phase
- High mortality rates fro natural causes
Montgomery SA, Cassano 1996, Harris 1997
Judd et al 2002,2003
Bipolar depression
Diagnosis
Obstacles :
1. Under diagnosis , misdiagnosis
2. Misdiagnosed as unipolar depression ( MDD )
3. Often treated symptomatically with antidepressant
drugs
4. Antidepressant drugs : Despite evidence that they
induce mania or rapid cycling, ADDs are the most
frequently prescribed medication
5. Management overlooked in favor of mania
Thomas A. M. Kramer : Medscape General medicine, 2004 ; 6 /2 :29
Bipolar depression
Underdiagnosis or misdiagnosis
Presentation :difficult to diagnose
1. Less dramatic
2. Inadequate data ( Poor history)
3. Type II presentations, absence of manic symptoms
4. Normal v/s hypomania ???
Thomas A. M. Kramer : Medscape General medicine, 2004 ; 6 /2 :29
Kemps et al : Psychiatric times , Vol XXIII /9 , Aug ’06
BIPOLAR DISORDER
ANXIETY IN BIPOLAR
• EMILKRAEPLIN –ANXIOUS MANIA-1921
• ANXIETY AS SYMPTOM
• ANXIETY –CO MORBID
• CHILDREN
ANXIETY –BIPOLAR SYMPTOMS
• RACING THOUGHTS
• SPEED
• MOTOR RESTLESSNESS
• AGITATION
• PRESSURE OF SPEECH
• IRRITABILITY
• GAD
• Cognitive
• Free floating
• worry
• difficulty concentrating
• Energy
• keyed up, on edge
• restlessness, tension
• easily fatigued
• difficulty falling/staying
asleep
• Mood
• irritability
• BPD II
• Cognitive
• Racing thoughts
• [difficulty concentrating]
• Energy
• motor agitation
• restlessness
• extreme fatigue
• [profound insomnia]
• Mood
• dysphoria, irritability
15% BIPOLAR HAVE OC SYMPTOMS
OBSESSION USED TO DESCRIBE MANIA –OBSESSED WITH T.V
OCD BIPOLAR
• COMPULSIONS
• PERFECTIONISM
• RELIGIOUSITY
• PUNCTUAL
• CHECKING
• RITUALISTIC
• DETAILED
• GOAL DIRECTEDACTIVITY
• SELF ESTEEM
• RELIGIOUS
• RESPONSIBLE
• LEADERSHIP
• RITUALISTIC
• DETAILED
PEDIATRIC BPD
TREATMENT OF BIPOLAR
 ANTI DEPRESSANTS
 MOOD STABILIZERS
 ANTIPSYCHOTICS
 OTHER
 rTMS
ANTI DEPRESSANTS IN BIPOLAR
ILLNESS
 CONTROVERSIAL
 COMMONLY USED
 DIAGNOSED AS UNIPOLAR DEPRESSION
 SOME ARE EFFECTIVE IN BPDEPRESSION
 LESS EFFICAY THAN LITHIUM
 NOT EFFECTIVE IN PROPHYLAXS
ANTI DEPRESSANTS
 ANTIDEPRESSANT INDUCED MANIA
 MIMICS MIXED PHASE
 SUICIDALITY IS COMMON
 AGITATION INCREASES
 RAPID CYCLING
 DESTABILISATION
Antidepressant-induced cycle acceleration in
bipolar disorder
10
8
6
4
2
0
Antidepressant-induced mania
in patients with unipolar
and bipolar depression
†
* ***
(n=10246) (n=3788) (n=125) (n=242) (n=48)
12
10
8
6
4
2
0
Peet 1994
ANTIDEPRESSANTS IN BPD
 CYCLOTHYMIA may switch to hypomania
 Young age
 Substance abuse
 Antidepressant associated
Chronic
Irritable
Dysphoria
El Mallakh and Karippot J Aff. Dis 2005
 Unique mode of action – Bidirectional mood stabilizer
 Clozapine like profile as an antagonist at multiple
receptors
 Moderate affinity for D2
 Greater affinity for 5HT2 to D2 ratio
 Modulates DA & other monoamine pathways with
antimanic and antidepressant properties
 No appreciable affinity for muscarinic & cholinergic
Intermittent blockade of D2 receptors & 5HT2A antagonist
No EPS
No TD
No se serum prolactin
 no menstrual irregularities
 no galactorrhoea
 no impotency
J Clin Psychiatry 2000;61(Suppl 8):31-33
Safest among all atypicals
CNPT2(2011) 12-23
 BIPOLAR DISORDER IS MORE COMMON THAN
WE THINK
 AVERAGE BIPOLAR DIAGNOSIS DELAYED BY
DECADE.
 PEOPLE WITH BPD SEPND MORE TIME IN
DEPRESSION
 SPECTRUM CONCEPT MAY ANSWER MANY
QUESTION
 THE QUESTION IS NOT
WHETHER THIS DEPRESSION IS BIPOLAR OR
NOT?
BUT
 HOW MUCH BIPOLAR THIS DEPRESSION IS?
Bipolar
Bipolar
Bipolar

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Bipolar

  • 2.
  • 3.
  • 5.
  • 6.
  • 7.  CATEGORICAL  WATER TIGHT  NO OVERLAPS  DISCRETE  PRESENCE OR ABSCENCE  DIMENSIONAL  SINGLE OR MULTIPLE FACTORS  PRESENT IN ALL  CLASSIFIED ACCORDING TO DEGREE
  • 8.
  • 9.
  • 10.
  • 11.  DENOTES TWO EXTREMES  EQUATES WITH MANIA THE HIGH  PATIENT DENIES BEING MANIAC  ACCEPTS DEPRESSION  EITHER MANIA OR DEPRESSION
  • 12.
  • 13.
  • 14.  ITALIAN PSYCHIATRIST  WORKED INFLORENCE  DESCRIBED CLASSIFICATION  MANIA, MELANCHOLIA,DEMEN TIA
  • 15.  German psychiatrist  Director of Sachsenberg mental hospital  Dysthymia mutabilis  Mixture of Dysthyma atra (Black depression) and Dysthyma candida (low-level mania).
  • 16.  Saltpetriere Hospital Paris  La folie circulaire 1951  Alternating Mania and Melancholia  Different from Mania and melancholia
  • 17.  French Psychiatrist  Collegue at Saltpetriete  Claimed that he was the first the describe cyclic illness  Tussle with Falret
  • 18.  GERMAN PSYCHATRIST  INTRODUCED THE TERM CYCLOTHYMIA  ASSOCIATE HECKER  CATATONIA  HEBEPHRENIA
  • 19.  GERMAN PSYCHIATRIST  GREAT CLASSIFIER  MANIC DEPRESSIVE PSYCHOSIS  DEMENTIA PRECOX  UNITARY CONCEPT
  • 20.  GERMAN  STUDENT OF WERNICKE  COINED BIPOLAR  AND UNIPOLAR
  • 21.  ASSOCIATE OF KLIEST  MULTIPLE SUBTYPES  CYCLOID PSYCHOSIS  POPULARIZED UNIPOLAR BIPOLAR
  • 22.
  • 23. Poles what is reality Eca survey  Incidence of Bipolar disorder is 1.2% (1988)  Ratio of Unipolar : Bipolar is 4:1 RECENT  6.4% (Judd &Akiskal 2003)
  • 24. % among psy patients  One third of Depressed outpatients (Cassano 1989)  45% of Depressed Outpatients (Benazzi 1997)  60% Depressed Ghaemi
  • 25.
  • 26.
  • 27.  BIPOLAR ILLNESS IS COMMONLY MISSED  48% INITIALDIAGNOSISWAS MISSED  54% DIAGNOSED AS UNIPOLAR DEP  34%AS BIPOLAR  AVERAGE ITTOOK 8YRSTO DIAGNOSEAS BPD
  • 28.
  • 29.
  • 30.
  • 31.
  • 32.
  • 33.
  • 34. FOLLOW UP OF PREPUBRTAL AND ADOLESCENT DEPRESSION
  • 35.
  • 36. HOW TO APPROACH BIPOLAR
  • 37. BIPOLAR Vs UNIPOLAR SAME OR DIFF
  • 38.  CLINICALLY DIFFERENT?  GENETICALLY DIFFERENT?  NEUROBOLOGICALLY DIFFERENT?  TREATMENT ?
  • 39. IF BOTH BD &UD ARE DIFFERENT
  • 40.
  • 42.
  • 43.
  • 44.
  • 45.
  • 46. BIPOLAR NOT NECESSARILY TWO OPPOSITE ENDS
  • 47. AGITATED DEPRESSION  RACING THOUGHTS  PSYCHOMOTOR AGITATION  IRRITABILITY  STRONG BIPOLAR FAMILY HISTORY  ANTI DEPRESSANT INDUCED DESTABILIZATION  Akiskal Benazzi 2004
  • 48.
  • 49.
  • 50.
  • 51.
  • 54.
  • 55.
  • 57. BIPOLAR DISORDER V DEPRESSION WITH MIXED HYPOMANIA BIPOLAR DISORDER VI BIPOLAR IN THE SETTING OF DEMENTIA
  • 58.
  • 59.
  • 61.
  • 62. DSM V  Better than DSM IV  MANIC, HYPOMANIC, DEPRESSVE EPISODE  No MIXED episode  NOS omitted  BIPOLAR I, II CYCLOTHYMIA, SUBSTANCE, OTHER MEDICAL CAUSES
  • 63. MIXED  MIXED FEAUTURES IS A SPECIFIER  DEPRESSIVE EPISODE WITH MIXED FEATURES- Agitated Depression  MANIC OR HYPOMANC EPISODE WITH MIXED FEATURES- Dysphoric Mania
  • 64. OTHER SPECIFIER  ANXIOUS DISTRESS  CATATONIC  MIXED  SEASONAL  MOOD CONGRUENT PSYCHOTIC  MOOD INCONGRUENT PSYCHOTIC  ATYPICAL  POST PARTUM ONSET 
  • 65. OTHER SPECIFIED BIPOLAR AND RELATED DISORDER  SHORT DURATION HYPOMANIC EPISODES AND MAJOR DEPRESSVE EPISODES  HYPOMANIC EPISODES WITH INSUFFECIENT SYMPTOMS AND MAJOR DEPRESSIVE DISORDER  HYPOMANIC EPISODE WITHOUT PRIOR DEPRESSIVE EPISODE  SHORT DURATION CYCLOTHYMIA
  • 66. Neurobiology OF MANIA AND BIPOLAR DISORDER* Ambiguous till date Biogenic amine neurotransmitters: Noradrenergic system: NE turnover increase in the cortical and thalamic areas of BD subjects where decrease in depression • Serotogenic system: Reduced 5-hydroxytryptamine (5- HT)1A receptor binding potential in raphe and hippocampus- amygdala of brain in depressed patients Dopaminergic system • DA agonists are effective antidepressants and are able to precipitate mania. • D2 receptor found in caudate, putamen, nucleus accumbens, cerebral cortex and hypothalmus is negativly coupled to adenylyl cyclase. Older antipsychotics act through blockage of D2 receptors , which eventualy result in extrpyramidal system (muscle rigidty , involuntry movement, pseudoparkinsonism)
  • 67.
  • 68.  Worldwide disorder  Age at onset : Adult , Children & Adolescent  Among the top 10 of GBD ( Global Burden of diseases)  Fifth / Sixth amongst reported disability  An under diagnosed and under treated disorder Bauer in, eds Tasman et al 2003
  • 69. Bipolar depression Disease Burden  Patients with onset in mid to late 20’s effectively lose 9 years of life, 12 years of normal health and 14 years of normal activity  Increase likelihood of divorce by 3 X Montgomery SA, Cassano GB, Management of bipolar disorder, 1996 , p5
  • 70. Bipolar depression Disease Burden  Years lived with disorder : Depression > Mania / Hypomania Comorbidity: - Anxiety disorders : 52% ( Panic, GAD, Social Phobia ) - Substance abuse disorder : 39%  Suicide - 10% to 19-20% , 15 -30 times > general population - At least 25% will attempt suicide - 80% suicide attempts / completed suicide occur in depressed phase - High mortality rates fro natural causes Montgomery SA, Cassano 1996, Harris 1997 Judd et al 2002,2003
  • 71. Bipolar depression Diagnosis Obstacles : 1. Under diagnosis , misdiagnosis 2. Misdiagnosed as unipolar depression ( MDD ) 3. Often treated symptomatically with antidepressant drugs 4. Antidepressant drugs : Despite evidence that they induce mania or rapid cycling, ADDs are the most frequently prescribed medication 5. Management overlooked in favor of mania Thomas A. M. Kramer : Medscape General medicine, 2004 ; 6 /2 :29
  • 72. Bipolar depression Underdiagnosis or misdiagnosis Presentation :difficult to diagnose 1. Less dramatic 2. Inadequate data ( Poor history) 3. Type II presentations, absence of manic symptoms 4. Normal v/s hypomania ??? Thomas A. M. Kramer : Medscape General medicine, 2004 ; 6 /2 :29 Kemps et al : Psychiatric times , Vol XXIII /9 , Aug ’06
  • 73.
  • 75.
  • 76. ANXIETY IN BIPOLAR • EMILKRAEPLIN –ANXIOUS MANIA-1921 • ANXIETY AS SYMPTOM • ANXIETY –CO MORBID • CHILDREN
  • 77. ANXIETY –BIPOLAR SYMPTOMS • RACING THOUGHTS • SPEED • MOTOR RESTLESSNESS • AGITATION • PRESSURE OF SPEECH • IRRITABILITY
  • 78. • GAD • Cognitive • Free floating • worry • difficulty concentrating • Energy • keyed up, on edge • restlessness, tension • easily fatigued • difficulty falling/staying asleep • Mood • irritability • BPD II • Cognitive • Racing thoughts • [difficulty concentrating] • Energy • motor agitation • restlessness • extreme fatigue • [profound insomnia] • Mood • dysphoria, irritability
  • 79. 15% BIPOLAR HAVE OC SYMPTOMS OBSESSION USED TO DESCRIBE MANIA –OBSESSED WITH T.V OCD BIPOLAR • COMPULSIONS • PERFECTIONISM • RELIGIOUSITY • PUNCTUAL • CHECKING • RITUALISTIC • DETAILED • GOAL DIRECTEDACTIVITY • SELF ESTEEM • RELIGIOUS • RESPONSIBLE • LEADERSHIP • RITUALISTIC • DETAILED
  • 81.
  • 82. TREATMENT OF BIPOLAR  ANTI DEPRESSANTS  MOOD STABILIZERS  ANTIPSYCHOTICS  OTHER  rTMS
  • 83. ANTI DEPRESSANTS IN BIPOLAR ILLNESS  CONTROVERSIAL  COMMONLY USED  DIAGNOSED AS UNIPOLAR DEPRESSION  SOME ARE EFFECTIVE IN BPDEPRESSION  LESS EFFICAY THAN LITHIUM  NOT EFFECTIVE IN PROPHYLAXS
  • 84. ANTI DEPRESSANTS  ANTIDEPRESSANT INDUCED MANIA  MIMICS MIXED PHASE  SUICIDALITY IS COMMON  AGITATION INCREASES  RAPID CYCLING  DESTABILISATION
  • 85. Antidepressant-induced cycle acceleration in bipolar disorder 10 8 6 4 2 0
  • 86. Antidepressant-induced mania in patients with unipolar and bipolar depression † * *** (n=10246) (n=3788) (n=125) (n=242) (n=48) 12 10 8 6 4 2 0 Peet 1994
  • 87. ANTIDEPRESSANTS IN BPD  CYCLOTHYMIA may switch to hypomania  Young age  Substance abuse
  • 88.  Antidepressant associated Chronic Irritable Dysphoria El Mallakh and Karippot J Aff. Dis 2005
  • 89.  Unique mode of action – Bidirectional mood stabilizer  Clozapine like profile as an antagonist at multiple receptors  Moderate affinity for D2  Greater affinity for 5HT2 to D2 ratio  Modulates DA & other monoamine pathways with antimanic and antidepressant properties  No appreciable affinity for muscarinic & cholinergic
  • 90.
  • 91.
  • 92. Intermittent blockade of D2 receptors & 5HT2A antagonist No EPS No TD No se serum prolactin  no menstrual irregularities  no galactorrhoea  no impotency J Clin Psychiatry 2000;61(Suppl 8):31-33 Safest among all atypicals
  • 93.
  • 95.
  • 96.  BIPOLAR DISORDER IS MORE COMMON THAN WE THINK  AVERAGE BIPOLAR DIAGNOSIS DELAYED BY DECADE.  PEOPLE WITH BPD SEPND MORE TIME IN DEPRESSION  SPECTRUM CONCEPT MAY ANSWER MANY QUESTION
  • 97.  THE QUESTION IS NOT WHETHER THIS DEPRESSION IS BIPOLAR OR NOT? BUT  HOW MUCH BIPOLAR THIS DEPRESSION IS?