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BIPOLAR DISORDERS
       :(:
                       Dapinderjit Gill, Ross University
       Bergen Regional Medical Center, Psych Clerkship
DEFINITIONS
BIPOLAR DISORDER

DEFINITION
Characterized by mania (i.e., have a manic or hypomanic episode) either alone or in
combination with depression      – Introductory Textbook of Psychiatry


Any of several psychological disorders of mood characterized usually by alternating
episodes of depression and mania
                                               – Merriam-Webster’s Dictionary

   Psychiatric diagnosis that describes a category of mood
    disorders defined by the presence of one or more episodes
    of abnormally elevate energy levels, cognition, and mood
    with or without one or more depressive episodes
                                 – Wikipedia.org
EPISODES
   Major Depressive Episode
       5 of 9 sx. of depression (one must be depressed mood or loss of interest or
        pleasure) and must be present for at least 2 weeks.

   Manic Episode
       3 of 7 sx. plus presence of an abnormally elevated, expansive, or irritable
        mood lasting at least one week.

   Mixed Episode
       Full criteria for both a manic and a depressive episode be met within a 1-
        week period

   Hypomanic Episode
       Elevated mood and other classic sx. that define mania but are not
        accompanied by delusional beliefs or hallucinations and are not severe
        enough to require hospitalization or markedly impair social and
        occupational functioning
CLASSIFICATIONS
CLASSIFICATIONS

BIPOLAR DISORDERS
Bipolar I

Bipolar II

Cyclothymic disorder

Bipolar disorder not otherwise specified
EPIDEMIOLOGY
EPIDEMIOLOGY
Recent National Comorbidity Study
Lifetime prevalence of nearly 2% for bipolar I and II combined.

More common in women than in men 3:2 but men tend to have earlier
onset than women
Median age of onset 25 years

The Global Burden of Disease
Bipolar disorders rank sixth

among the world’s most disabling illnesses
ETIOLOGY AND
PATHOPHYSIOLOGY
ETIOLOGY AND PATHOPHYSIOLOGY
GENETIC
Significantly increases rates of bipolar disorder in first degree relatives of
bipolar parents
Twin and adoption studies have provided evidence that mood disorders
are genetic in addition to being familial
      Monozygotic-to-dizygotic ratio approx. 4:1

Genes of interest:
    Associations with bipolar disorder include D-amino0acid oxidase gene
      (G72), brain0derived neurotrophic factor gene (BDNF), neuregulin 1 gene
      (NRG1), dysbindin (DTNBP1)
    Genes associated with circadian rhythm (CLOCK, TIMELESS, PERIOD3)
      have also been implicated
DSM-VI-TR BIPOLAR
DISORDERS
BIPOLAR I
BIPOLAR I
 Occurrence of at least one manic or mixed episode

DSM-VI-TR
 Six separate criteria sets
      Single Manic Episode
      Most Recent Episode Hypomanic
      Most Recent Episode Manic
      Most Recent Episode Mixed
      Most Recent Episode Depressed
      Most Recent Episode Unspecified
BIPOLAR I

SINGLE MANIC EPISODE 296.0x

A
Presence of only one Manic Episode and no past MDE

B
The Manic Episode is not better accounted for by
Schizoaffective Disorder and is not superimposed on
Schizophrenia, Schizophreniform Disorder, Delusional Disorder,
or Psychotic Disorder Not Otherwise Specified
BIPOLAR I
MOST RECENT EPISODE HYPOMANIC 296.40
A
Currently (or most recently) in a Hypomanic Episode
B
There has previously been at least one Manic Episode or Mixed
Episode
C
The mood sx. cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning
D
The mood episodes in Criteria A and B are not better accounted for by
Schizoaffective Disorder and are not superimposed on Schizophrenia,
Schizophreniform Disorder, Psychotic Delusional Disorder Not
Otherwise Specified
BIPOLAR I
MOST RECENT EPISODE MANIC 296.4x

A
Currently (or most recently) in a
    Manic Episode

B
There has previously been at least one Major Depressive Episode,
Manic Episode, or Mixed Episode

C
The mood episodes in Criteria A and B are not better accounted for by
Schizoaffective Disorder and are not superimposed on Schizophrenia,
Schizophreniform Disorder, Psychotic Delusional Disorder Not
Otherwise Specified
BIPOLAR I
MOST RECENT EPISODE MIXED 296.6x

A
Currently (or most recently) in a Mixed Episode

B
There has previously been at least one Major Depressive Episode,
Manic Episode, Mixed Episode

C
The mood episodes in Criteria A and B are not better accounted for by
Schizoaffective Disorder and are not superimposed on Schizophrenia,
Schizophreniform Disorder, Psychotic Delusional Disorder Not
Otherwise Specified
BIPOLAR I
MOST RECENT EPISODE DEPRESSED 296.5x

A
Currently (or most recently) in a Major Depressive Episode

B
There has previously been at least one Manic Episode or Mixed
Episode

C
The mood episodes in Criteria A and B are not better accounted for by
Schizoaffective Disorder and are not superimposed on Schizophrenia,
Schizophreniform Disorder, Psychotic Delusional Disorder Not
Otherwise Specified
BIPOLAR I
MOST RECENT EPISODE UNSPECIFIED 296.7
A
Criteria, except for duration, are currently (or mostly recently) met for a Manic, a
Hypomanic, a Mixed, or a Major Depressive Episode
B
There has previously been at least one Manic Episode or Mixed Episode
C
The mood sx. cause clinically significant distress or impairment in social, occupational,
or other important areas of functioning
D
The mood episodes in Criteria A and B are not better accounted for by Schizoaffective
Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder,
Psychotic Delusional Disorder Not Otherwise Specified
E
The mood symptoms in Criteria A and B are not due to the direct physiological effects
of a substance or a general medical condition
BIPOLAR II
BIPOLAR II
   Characterized by periods of hypomania that
    typically occur either before or after periods of
    depression but also may occur independently

   May lead to personal, social, or work
    difficulties but are not sufficiently severe to
    require hospitalization

   High rate of comorbidity with other disorders
    such as substance abuse

   Experience greater burden of depressive sx.
    than bipolar I
BIPOLAR II
RECURRENT MAJOR DEPRESSIVE EPISODES WITH HYPOMANIC EPISODES 269.89
A
Presence (or history) of one or more Major Depressive Episodes
B
Presence (or history) of at least one Hypomanic Episode
C
There has never been a Manic Episode or Mixed Episode
D
The mood episodes in Criteria A and B are not better accounted for by
Schizoaffective Disorder and are not superimposed on Schizophrenia,
Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified
E
The sx. cause clinically significant distress or impairment in social, occupational, or
other important areas of functioning
CYCLOTHYMIC
DISORDER
CYCLOTHYMIC DISORDER
 Mildest form of bipolar disorders

 Mild swings between two poles of

  depression and hypomania
 In hypomania, patient is not socially
  or professionally incapacitated
 During depressed phase, patient has
  some sx. of depression but these are
  not severe enough to meet criteria
  a full major depressive episode
CYCLOTHYMIC DISORDER
301.13
A
For at least 2 years, the presence of numerous periods with hypomanic sx. and numerous
periods with depressive sx. that do not meet criteria for a Major Depressive Episode.
B
During the above 2 year period, the person has not been without the sx. in Criterion A for
more than 2 months at a time
C
No Major Depressive Episode, Manic Episode, or Mixed Episode has been present during the
first 2 years of the disturbance
D
The sx. in Criterion A are not better accounted for by Schizoaffective Disorder and are not
superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic
Disorder Not Otherwise Specified.
E
The sx. are not due to direct physiological effects of substance or a general medical condition
F
The sx. cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning
BIPOLAR DISORDER
NOT OTHERWISE SPECIFIED
BIPOLAR DISORDER NOT OTHERWISE
SPECIFIED
296.80
1
Very rapid alternation (over days) between manic sx. and depressive sx. that meet sx.
threshold criteria but not minimal duration criteria for Manic, Hypomanic, or Major
Depressive Episodes
2
Recurrent Hypomanic Episodes without intercurrent
    depressive sx.
3
A Manic or Mixed Episode superimposed on Delusional
    Disorder, residual Schizophrenia, or Psychotic Disorder
    Not Otherwise Specified
4
Hypomanic Episodes, along with chronic depressive
    symptoms, that are too infrequent to qualify for a
    diagnosis of Cyclothymic Disorder
5
Situations in which the clinician has concluded that a Bipolar Disorder is present but is
unable to determine whether it is primary, due to a general medical condition, or
substance induced
DIFFERENTIAL
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
 General Medical conditions

      Such as hypothyroidism and SLEs

 Specific extrinsic factors

      Drugs of abuse, sedatives, tranquilizers, antihypertensives,
       glucocorticoids etc.

 Mania vs. Schizophrenia

 Bereavement
      presence of the sx. considered a normal reaction in this case
TREATMENT
TREATMENT
   Lithium, Valproate, and Carbamazepine FDA approved for acute
    Mania
   Lamotrigine and a few others are approved for maintenance
    treatment of bipolar disorders
   Other anticonvulsant drugs (gabapentin and topiramate) have
    been used to treat bipolar patients but have had mixed results
   All SGAs (expect clozapine) approved to treat acute mania, and
    several have received indications for maintenance treatment of
    bipolar disorder or as adjuncts to lithium or valproate.
   Electroconvulsive therapy is highly effective in treatment of manic
    patients when medication is ineffective
LITHIUM
LITHIUM CARBONATE (Eskaliath, Eskalith CR)
Cap: 300 mg; Manic episode
    >= 12yo 1800mg/d in divided doses given TID or QID. Desired serum level 1-
       1.5mEq/L
    Long-term: 300mg TID or QID
Tab,ER: 450mg BID
    Desired serum levels of 0.6-1.2mEq/L
    Pregnancy rating: C: not rated; contraindicated for breast feeding

LITHIUM CITRATE
Syr: 300mg/5ml; Manic episode
>= 12 yo 600mg TID to serum level 1-15.mEq/L
Long-term: 300mg TID or QID to serum level 0.6-1.2mEq/L
Pregnancy rating: D: Positive evidence of risk : use only when no safer
alternative exists for a serious problem; contraindicated for breast feeding
DIVALPROEX SODIUM (DEPAKOTE)
 Valproate sodium and Valproic acid in a 1:1 ratio; Tab, delay:
   125mg, 250mg, 500mg
 Bipolar Disorder: Manic Episodes: Adult: Initial 750mg divided
   doses; Titrate rapidly to clinical effect; Max: 60mg/kg
 Hepatotoxic, teratogenic, pancreatitis

 Pregnancy rating: D: positive evidence of risk: use only when
   no safer alternative exists for a serious problem
 Contraindicated in breast feeding
CARBAMAZEPINE (EQUETRO)
 Cap, ER: 100mg, 200mg, 300mg

 Bipolar I: Acute Manic and Mixed Episodes

 Adult: Initial 400mg/d divided dose BID; Titrate to 200mg/d;
  Max: 1600mg/d
 Pregnancy rating: D: positive evidence of risk: use only when
  no safer alternative exists for a serious problem
 Contraindicated in breast feeding
LAMOTRIGINE (LAMICTAL)
   Chewtab: 2mg, 5mg, 25mg; Tab: 25mg, 100mg, 150mg, 200mg
   Bipolar I: Maintenance: Adults: Patient not taking Carbamazepine,
    other enzyme-inducing drugs (if pt. is on these drugs please refer to
    PDR):
     Week 1+2: 25mg/d; Week 3+4: 50mg/d; Week 5: 100mg/d; Week 6+7:
       200mg/d
   Serious rash, Steven-Johnson syndrome
   Adjust dose for hepatic and renal insufficiency
   Pregnancy rating: C: risk cannot be ruled out
   Contraindicated in breast feeding
ARIPIPRAZOLE (ABILIFY)
   Atypical antipsychotic
   Inj: 7.5 mg/ml; Sol: 1mg/ml; Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg
   Adults: Bipolar Disorder: Acute Manic and Mixed Episodes
       PO: Initial 30mg QD; Titrate

   Agitation Associated with Bipolar Disorder, Manic or Mixed
       Inj: Initial 9.75mg IM; Max: 30mg/d; Initiate PO therapy as soon as possible

   Pregnancy rating: D: positive evidence of risk: use only when no safer
    alternative exists for a serious problem

   Contraindicated in breast feeding
RISPERIDONE (RISPERDAL)
 Atypical antipsychotic

 Sol: 1mg/ml; Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg

 Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults:
  Monotherapy or Adjunct Therapy with Lithium or Valproate
      Initial 2-3mg QD; Titrate: increase by 1mg QD; Max: 6mg/d

 Adjust dose for hepatic and renal insufficiency

 Pregnancy rating: C: risk cannot be ruled out

 Contraindicated in breast feeding
ZIPRASODONE (GEODON)
 Atypical antipsychotic

 Cap: 20mg, 40mg, 60mg, 80mg

 Bipolar Disorder: Acute Manic and Mixed Episodes: Adults:
      Initial 40mg BID with food; Titrate: increase to 60-80mg BID on
       second day of treatment and maintain 40-80mg BID

 Pregnancy rating: C: risk cannot be ruled out

 Contraindicated in breast feeding
QUETIAPINE FUMARATE (SEROQUEL)
   Atypical antipsychotic
   Tab: 25mg, 50mg, 100mg, 200mg, 300mg, 400mg
   Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults:
    Monotherapy or Adjunct Therapy with Lithium or Valproate
     Initial 100mg/d BID; Titrate: increase to 400mg/d on day 4 with
       increments of up to 100mg/d BID. Adjust doses up to 800mg/d by
       day 6 in increments of not greater than 200mg/d; Max: 800mg/d
   Adjust dose for hepatic insufficiency
   Pregnancy rating: C: risk cannot be ruled out
   Contraindicated in breast feeding
OLANZAPINE (ZYPREXA)
   Atypical antipsychotic; combination with Fluoxetine HCl (Symbyax,
    different strengths and dosages, refer to PDR)
   Inj: 10mg; Tab: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg; Tab,
    dissolve: 5mg, 10mg, 15mg, 20mg
   Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults:
    Monotherapy: PO: Initial 10-15mg QD
   Adjunct Therapy with Lithium or Valproate: Initial 10mg QD;
    Titrate: adjust by 5mg/d; Max: 20mg/d
   Maintenance: Monotherapy: 5-20mg/d
   Agitation associated with bipolar mania: Inj: Initial 10mg IM; Max: 3
    doses of 10mg IM q2-4h. May initiate PO therapy when clinically
    appropriate.
   Pregnancy rating: C: risk cannot be ruled out; Contraindicated in
    breast feeding
TREATMENT

KEY POINTS
After an episode of mania, patient should receive maintenance
medication
Advise the importance of getting sufficient sleep and following
sensible sleep hygiene measures
supportive psychotherapy to help them
  cope with consequences and maintain
  their self-esteem
THANK YOU
REFERENCES
 Donald W. Black, Nancy C. Andreasen. Introductory Textbook
  of Psychiatry. 5th Edition. pp. 141-168.
 Merriam-Webster’s Dictionary

 Wikipedia.org, “Bipolar Disorders”. Last accessed April 20
  2011. http://en.wikipedia.org/wiki/Bipolar_disorder#
  Signs_and_symptoms
 PDR Pharmacopoeia Pocket Dosing Guide. 2007.Bristol-
  Myers Squibb and Otsuka America Pharmaceuticals, Inc. pp.
  266- 269

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Bipolar Disorders

  • 1. BIPOLAR DISORDERS :(: Dapinderjit Gill, Ross University Bergen Regional Medical Center, Psych Clerkship
  • 3. BIPOLAR DISORDER DEFINITION Characterized by mania (i.e., have a manic or hypomanic episode) either alone or in combination with depression – Introductory Textbook of Psychiatry Any of several psychological disorders of mood characterized usually by alternating episodes of depression and mania – Merriam-Webster’s Dictionary  Psychiatric diagnosis that describes a category of mood disorders defined by the presence of one or more episodes of abnormally elevate energy levels, cognition, and mood with or without one or more depressive episodes – Wikipedia.org
  • 4. EPISODES  Major Depressive Episode  5 of 9 sx. of depression (one must be depressed mood or loss of interest or pleasure) and must be present for at least 2 weeks.  Manic Episode  3 of 7 sx. plus presence of an abnormally elevated, expansive, or irritable mood lasting at least one week.  Mixed Episode  Full criteria for both a manic and a depressive episode be met within a 1- week period  Hypomanic Episode  Elevated mood and other classic sx. that define mania but are not accompanied by delusional beliefs or hallucinations and are not severe enough to require hospitalization or markedly impair social and occupational functioning
  • 6. CLASSIFICATIONS BIPOLAR DISORDERS Bipolar I Bipolar II Cyclothymic disorder Bipolar disorder not otherwise specified
  • 8. EPIDEMIOLOGY Recent National Comorbidity Study Lifetime prevalence of nearly 2% for bipolar I and II combined. More common in women than in men 3:2 but men tend to have earlier onset than women Median age of onset 25 years The Global Burden of Disease Bipolar disorders rank sixth among the world’s most disabling illnesses
  • 10. ETIOLOGY AND PATHOPHYSIOLOGY GENETIC Significantly increases rates of bipolar disorder in first degree relatives of bipolar parents Twin and adoption studies have provided evidence that mood disorders are genetic in addition to being familial  Monozygotic-to-dizygotic ratio approx. 4:1 Genes of interest:  Associations with bipolar disorder include D-amino0acid oxidase gene (G72), brain0derived neurotrophic factor gene (BDNF), neuregulin 1 gene (NRG1), dysbindin (DTNBP1)  Genes associated with circadian rhythm (CLOCK, TIMELESS, PERIOD3) have also been implicated
  • 13. BIPOLAR I  Occurrence of at least one manic or mixed episode DSM-VI-TR  Six separate criteria sets  Single Manic Episode  Most Recent Episode Hypomanic  Most Recent Episode Manic  Most Recent Episode Mixed  Most Recent Episode Depressed  Most Recent Episode Unspecified
  • 14. BIPOLAR I SINGLE MANIC EPISODE 296.0x A Presence of only one Manic Episode and no past MDE B The Manic Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified
  • 15. BIPOLAR I MOST RECENT EPISODE HYPOMANIC 296.40 A Currently (or most recently) in a Hypomanic Episode B There has previously been at least one Manic Episode or Mixed Episode C The mood sx. cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified
  • 16. BIPOLAR I MOST RECENT EPISODE MANIC 296.4x A Currently (or most recently) in a Manic Episode B There has previously been at least one Major Depressive Episode, Manic Episode, or Mixed Episode C The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified
  • 17. BIPOLAR I MOST RECENT EPISODE MIXED 296.6x A Currently (or most recently) in a Mixed Episode B There has previously been at least one Major Depressive Episode, Manic Episode, Mixed Episode C The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified
  • 18. BIPOLAR I MOST RECENT EPISODE DEPRESSED 296.5x A Currently (or most recently) in a Major Depressive Episode B There has previously been at least one Manic Episode or Mixed Episode C The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified
  • 19. BIPOLAR I MOST RECENT EPISODE UNSPECIFIED 296.7 A Criteria, except for duration, are currently (or mostly recently) met for a Manic, a Hypomanic, a Mixed, or a Major Depressive Episode B There has previously been at least one Manic Episode or Mixed Episode C The mood sx. cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified E The mood symptoms in Criteria A and B are not due to the direct physiological effects of a substance or a general medical condition
  • 21. BIPOLAR II  Characterized by periods of hypomania that typically occur either before or after periods of depression but also may occur independently  May lead to personal, social, or work difficulties but are not sufficiently severe to require hospitalization  High rate of comorbidity with other disorders such as substance abuse  Experience greater burden of depressive sx. than bipolar I
  • 22. BIPOLAR II RECURRENT MAJOR DEPRESSIVE EPISODES WITH HYPOMANIC EPISODES 269.89 A Presence (or history) of one or more Major Depressive Episodes B Presence (or history) of at least one Hypomanic Episode C There has never been a Manic Episode or Mixed Episode D The mood episodes in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Psychotic Delusional Disorder Not Otherwise Specified E The sx. cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
  • 24. CYCLOTHYMIC DISORDER  Mildest form of bipolar disorders  Mild swings between two poles of depression and hypomania  In hypomania, patient is not socially or professionally incapacitated  During depressed phase, patient has some sx. of depression but these are not severe enough to meet criteria a full major depressive episode
  • 25. CYCLOTHYMIC DISORDER 301.13 A For at least 2 years, the presence of numerous periods with hypomanic sx. and numerous periods with depressive sx. that do not meet criteria for a Major Depressive Episode. B During the above 2 year period, the person has not been without the sx. in Criterion A for more than 2 months at a time C No Major Depressive Episode, Manic Episode, or Mixed Episode has been present during the first 2 years of the disturbance D The sx. in Criterion A are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified. E The sx. are not due to direct physiological effects of substance or a general medical condition F The sx. cause clinically significant distress or impairment in social, occupational, or other important areas of functioning
  • 27. BIPOLAR DISORDER NOT OTHERWISE SPECIFIED 296.80 1 Very rapid alternation (over days) between manic sx. and depressive sx. that meet sx. threshold criteria but not minimal duration criteria for Manic, Hypomanic, or Major Depressive Episodes 2 Recurrent Hypomanic Episodes without intercurrent depressive sx. 3 A Manic or Mixed Episode superimposed on Delusional Disorder, residual Schizophrenia, or Psychotic Disorder Not Otherwise Specified 4 Hypomanic Episodes, along with chronic depressive symptoms, that are too infrequent to qualify for a diagnosis of Cyclothymic Disorder 5 Situations in which the clinician has concluded that a Bipolar Disorder is present but is unable to determine whether it is primary, due to a general medical condition, or substance induced
  • 29.
  • 30. DIFFERENTIAL DIAGNOSIS  General Medical conditions  Such as hypothyroidism and SLEs  Specific extrinsic factors  Drugs of abuse, sedatives, tranquilizers, antihypertensives, glucocorticoids etc.  Mania vs. Schizophrenia  Bereavement  presence of the sx. considered a normal reaction in this case
  • 32. TREATMENT  Lithium, Valproate, and Carbamazepine FDA approved for acute Mania  Lamotrigine and a few others are approved for maintenance treatment of bipolar disorders  Other anticonvulsant drugs (gabapentin and topiramate) have been used to treat bipolar patients but have had mixed results  All SGAs (expect clozapine) approved to treat acute mania, and several have received indications for maintenance treatment of bipolar disorder or as adjuncts to lithium or valproate.  Electroconvulsive therapy is highly effective in treatment of manic patients when medication is ineffective
  • 33. LITHIUM LITHIUM CARBONATE (Eskaliath, Eskalith CR) Cap: 300 mg; Manic episode  >= 12yo 1800mg/d in divided doses given TID or QID. Desired serum level 1- 1.5mEq/L  Long-term: 300mg TID or QID Tab,ER: 450mg BID  Desired serum levels of 0.6-1.2mEq/L  Pregnancy rating: C: not rated; contraindicated for breast feeding LITHIUM CITRATE Syr: 300mg/5ml; Manic episode >= 12 yo 600mg TID to serum level 1-15.mEq/L Long-term: 300mg TID or QID to serum level 0.6-1.2mEq/L Pregnancy rating: D: Positive evidence of risk : use only when no safer alternative exists for a serious problem; contraindicated for breast feeding
  • 34. DIVALPROEX SODIUM (DEPAKOTE)  Valproate sodium and Valproic acid in a 1:1 ratio; Tab, delay: 125mg, 250mg, 500mg  Bipolar Disorder: Manic Episodes: Adult: Initial 750mg divided doses; Titrate rapidly to clinical effect; Max: 60mg/kg  Hepatotoxic, teratogenic, pancreatitis  Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem  Contraindicated in breast feeding
  • 35. CARBAMAZEPINE (EQUETRO)  Cap, ER: 100mg, 200mg, 300mg  Bipolar I: Acute Manic and Mixed Episodes  Adult: Initial 400mg/d divided dose BID; Titrate to 200mg/d; Max: 1600mg/d  Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem  Contraindicated in breast feeding
  • 36. LAMOTRIGINE (LAMICTAL)  Chewtab: 2mg, 5mg, 25mg; Tab: 25mg, 100mg, 150mg, 200mg  Bipolar I: Maintenance: Adults: Patient not taking Carbamazepine, other enzyme-inducing drugs (if pt. is on these drugs please refer to PDR):  Week 1+2: 25mg/d; Week 3+4: 50mg/d; Week 5: 100mg/d; Week 6+7: 200mg/d  Serious rash, Steven-Johnson syndrome  Adjust dose for hepatic and renal insufficiency  Pregnancy rating: C: risk cannot be ruled out  Contraindicated in breast feeding
  • 37. ARIPIPRAZOLE (ABILIFY)  Atypical antipsychotic  Inj: 7.5 mg/ml; Sol: 1mg/ml; Tab: 2mg, 5mg, 10mg, 15mg, 20mg, 30mg  Adults: Bipolar Disorder: Acute Manic and Mixed Episodes  PO: Initial 30mg QD; Titrate  Agitation Associated with Bipolar Disorder, Manic or Mixed  Inj: Initial 9.75mg IM; Max: 30mg/d; Initiate PO therapy as soon as possible  Pregnancy rating: D: positive evidence of risk: use only when no safer alternative exists for a serious problem  Contraindicated in breast feeding
  • 38. RISPERIDONE (RISPERDAL)  Atypical antipsychotic  Sol: 1mg/ml; Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg  Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy or Adjunct Therapy with Lithium or Valproate  Initial 2-3mg QD; Titrate: increase by 1mg QD; Max: 6mg/d  Adjust dose for hepatic and renal insufficiency  Pregnancy rating: C: risk cannot be ruled out  Contraindicated in breast feeding
  • 39. ZIPRASODONE (GEODON)  Atypical antipsychotic  Cap: 20mg, 40mg, 60mg, 80mg  Bipolar Disorder: Acute Manic and Mixed Episodes: Adults:  Initial 40mg BID with food; Titrate: increase to 60-80mg BID on second day of treatment and maintain 40-80mg BID  Pregnancy rating: C: risk cannot be ruled out  Contraindicated in breast feeding
  • 40. QUETIAPINE FUMARATE (SEROQUEL)  Atypical antipsychotic  Tab: 25mg, 50mg, 100mg, 200mg, 300mg, 400mg  Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy or Adjunct Therapy with Lithium or Valproate  Initial 100mg/d BID; Titrate: increase to 400mg/d on day 4 with increments of up to 100mg/d BID. Adjust doses up to 800mg/d by day 6 in increments of not greater than 200mg/d; Max: 800mg/d  Adjust dose for hepatic insufficiency  Pregnancy rating: C: risk cannot be ruled out  Contraindicated in breast feeding
  • 41. OLANZAPINE (ZYPREXA)  Atypical antipsychotic; combination with Fluoxetine HCl (Symbyax, different strengths and dosages, refer to PDR)  Inj: 10mg; Tab: 2.5mg, 5mg, 7.5mg, 10mg, 15mg, 20mg; Tab, dissolve: 5mg, 10mg, 15mg, 20mg  Bipolar I Disorder: Acute Manic and Mixed Episodes: Adults: Monotherapy: PO: Initial 10-15mg QD  Adjunct Therapy with Lithium or Valproate: Initial 10mg QD; Titrate: adjust by 5mg/d; Max: 20mg/d  Maintenance: Monotherapy: 5-20mg/d  Agitation associated with bipolar mania: Inj: Initial 10mg IM; Max: 3 doses of 10mg IM q2-4h. May initiate PO therapy when clinically appropriate.  Pregnancy rating: C: risk cannot be ruled out; Contraindicated in breast feeding
  • 42. TREATMENT KEY POINTS After an episode of mania, patient should receive maintenance medication Advise the importance of getting sufficient sleep and following sensible sleep hygiene measures supportive psychotherapy to help them cope with consequences and maintain their self-esteem
  • 44. REFERENCES  Donald W. Black, Nancy C. Andreasen. Introductory Textbook of Psychiatry. 5th Edition. pp. 141-168.  Merriam-Webster’s Dictionary  Wikipedia.org, “Bipolar Disorders”. Last accessed April 20 2011. http://en.wikipedia.org/wiki/Bipolar_disorder# Signs_and_symptoms  PDR Pharmacopoeia Pocket Dosing Guide. 2007.Bristol- Myers Squibb and Otsuka America Pharmaceuticals, Inc. pp. 266- 269

Hinweis der Redaktion

  1. Apart of Mood Disorders Which have high prevalence, morbidity and even mortality rate. Understanding these disorders are important for all of us because patients generally come with complaints about insomnia, fatigue, or unexplained pain and seek primary medical care which will most likely effect all of us in this room today. Misdiagnosing and not treating can be costly and disabling if not done correctly. NEXT SLIDE
  2. Before we start, we need to go through a few definitions to understand the spectrum of bipolar disorders NEXT SLIDE
  3. On this slide, I’ve places a few definitions of bipolar disorder… and for those that are going to go home and wikipedia bipolar disorders after this lecture, I’ve gone ahead and added the definition to the bottom there for you… but over all, bipolar disorder is when one’s mood cycles through periods of mania to a baseline or depressive state. But the term bipolar disorder actually did not come into play until 1980’s in DSM-3 and has an interesting origin… it has been one of the oldest known illnesses with mention of symptoms in early medical records and can be noticed as far back as the second century (200A.D.)  Aretaeus of Cappadocia (city in ancient Turkey) first recognized sx. of mania and depression and felt they could be linked to each other. This went unnoticed and unsubstantiated until 1650, when scientist Richard Burton wrote a book called The Anatomy of Melancholia which focused more on depression. 1854, Jules Falret coined the term “ folie circulaire ” which translates to circular insanity and established a link between depression and suicide. His work lead to the term bipolar disorder as he was able to find a distinction between moments of depression and heightened moods. He recognized this to be different from simple depression and finally in 1875 his recorded findings were termed manic-depressive psychosis, a psychiatric disorder. He also recognized that the diseases seemed to be found in certain families, recognizing a genetic link. At that time, the disease was still lumped with other mental illnesses until Francois Baillarger who believed there was a major distinction and characterized the depressive phase of the disease which allowed bipolar disorder to receive its own classification. Then in 1913, Emil Krapelin established the term manic-depressive disorder with a study that looked at the effects of depression and a small portion about the manic state. And then in 1980, the term bipolar disorder replaced manic-depressive disorder as a diagnostic term found in the DSM-3 (APA - is a serious mental illness in which common emotions become intensely and often unpredictably magnified. Individuals with bipolar disorder can quickly swing from extremes of happiness, energy and clarity to sadness, fatigue and confusion. These shifts can be so devastating that individuals may choose suicide. All people with bipolar disorder have manic episodes — abnormally elevated or irritable moods that last at least a week and impair functioning. But not all become depressed. ) NEXT SLIDE
  4. Episodes serve as the building blocks for the disorder diagnosis so it is important to know these… and to keep in mind, with these episodes, the mood disturbances must be sufficiently severe to cause marked impairment or to require hospitalization and cannot be due to physiological effect of drugs of abuse, medications, or a general medical conditions. More details about episodes is outlined in the sheets in front of you but in general… For MDE – you need 5 out of 9 sx. for at least a 2 week period ie, depressed mood, anhedonia, weight loss/gain decrease/increase appetite, insomnia/hypersomnia, psychomotor retardation/agitation, fatigue, guilt, inability to concentrate thoughts of death/SI As for a Manic episode, it is defined by an abnormally elevated, expansive, or irritable mood lasting at least one week with 3 of 7 symptoms… which include grandiosity, decreased need for sleep, talkative than usual or pressure to keep talking, flight of ideas/racing thoughts, distractibility, increased goal-directed activity, excessive involvement in pleasurable activities (read mixed and hypomanic episode) Major Depressive Episode A: Five of the following sx. have been present during the same 2-week period and represent a change from previous functioning; at least one of the sx. is either depressed mood or loss of interest or pleasure. Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by other (NOTE: in children and adolescents, can be irritable mood) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day Fatigue or loss of energy nearly every day Feelings of worthlessness or excessive or inappropriate guilt nearly every day Diminished ability to think or concentrate, or indecisiveness, nearly every day Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B: The sx. do not meet criteria for a Mixed Episode C: The sx. cause clinically significant distress or impairment in social, occupational, or other important areas of functioning D: The sx. are not due to the direct physiological effects of a substance or a general medical condition E: The sx. are not better accounted for by Bereavement. The sx. persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic sx., or psychomotor retardation Manic Episode A: A distinct period of abnormally and persistently elevated, expansive, or irritable mood, last at least one week B: During the period of mood disturbance, three or more of the following sx. have persisted and have been present to a significant degree: Inflated self-esteem or grandiosity Decreased need for sleep More talkative than usual or pressure to keep talking Flight of ideas or subjective experience that thoughts are racing Distractibility Increase in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activities that have a high potential for painful consequences C: The sx. do not meet the criteria for a Mixed Episode D: The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psycotic features. E: The sx. are not due to the direct physiological effects of a substance or a general medical condition Mixed Episode A: The criteria are met both for a Manic Episode and for a Major Depressive Episode (except duration) nearly every day during at least a one week period B: The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psycotic features. C: The sx. are not due to the direct physiological effects of a substance or a general medical condition Hypomanic Episode A: A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood B: During the period of mood disturbance, three or more of the following sx. have persisted and have been present to a significant degree: Inflated self-esteem Decreased need for sleep More talkative than usual or pressure to keep talking Flight of ideas or subjective experience that thought are racing Distractibility Increased in goal-directed activity or psychomotor agitation Excessive involvement in pleasurable activities that have a high potential for painful consequences C: The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic D: The disturbance in mood and the change in functioning are observable by others E: The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features F: The sx. are not due to the direst physiological effects of a substance or a general medical condition
  5. Bipolar I has more subtype based on DSM-IV which I’ll get into later on…
  6. A little epidemiology…
  7. There is a lifetime prevalence of nearly 2% for bipolar I and II combined Its more common in women but men tend to have earlier onset… And the median age of onset is 25 years… One thing I found interesting was that bipolar disorders rank sixth among the world’s most disabling illnesses NEXT SLIDE
  8. Etiology and pathophysiology
  9. A lot of the etiology and pathophysiology is unknown but there has been evidence of genetics playing a roll as seen from twin and adoption studies…. At the bottom there I’ve listed a view genes of interest for those that might be interested…. NEXT SLIDE
  10. And now going into each class of bipolar disorders, we are going to start off with bipolar 1
  11. Bipolar I
  12. (read definition then add typical Bipolar I finding with depression) But most often seen by recurrent episodes of both mania and depression, which may be separated by intervals of months to years Interepisode functioning may be good or even excellent
  13. For single manic episode, only one manic episode with now major depressive episode in the past and the manic episode should be differentiated from other psychotic disorders
  14. Most recent episode hypomanic criteria set, obviously, the current or most recent episode should be hypomanic and there should be a previous manic or mixed episode and there should be significant impairment in functioning but not marked impairment in this case… and also, like the other one, you would need to distinguish it from other psychotic disorders
  15. Most recent episode manic, similar to the last one but with the current or most recent episode a manic one… and in this one, you can also have an added previous major depressive episode
  16. Most recent episode mixed… I think you guys get the idea… recent episode being mixed.
  17. And in most recent episode depressed being depressed
  18. And then there is most recent episode unspecified… this is pretty much used when the criteria for duration is not met for each episode…
  19. Bipolar II
  20. Generally here you see periods of hypomania cycling with or without periods of depression but both hypomania and depression need to be present the main difference is that the disorder does not lead to sufficiently severe difficulties or hospitalizations…
  21. This is the DSM 4 criteria for bipolar II Once again, the presence of both major depressive episodes and hypomanic episodes need to be present with an absence of manic or mixed
  22. cyclothymic disorder
  23. This is the mildest form of bipolar disorders and the main thing here is that it the depressive sx. do not meet the full criteria of major depressive episode…. but you still have the patient swinging between the two poles of depression and hypomania…
  24. This is the DSM 4 criteria The patient needs to have the presence of episodes for at least two years NOTE: In children and adolescents, the duration must be at least 1 year
  25. The bipolar disorder not otherwise specified category includes disorders with bipolar features that do not meet criteria for any specific Bipolar Disorder. So these are rapid alternations, usually over days, that don’t meet the minimal duration criteria for episodes And recurrent hypomanic episodes without intercurrent depressive sx. or if there is a manic or mixed episode superimposed on a psychotic disorder or if the clinician can not tell if the disorder is primary or secondary to a medical condition or substance induced
  26. Coming up with a differential diagnosis is very important when assessing bipolar disorders NEXT SLIDE
  27. As you may know, many different substances and conditions can precipitate sx. similar to those seen in bipolar disorders and its very important to differentiate these illnesses because the treatment can vary vastly.
  28. Things that need to be considered are medical conditions, extrinsic factors, schizophrenia and bereavement to name a few…. (I’ve listed here a few things that you need to keep in mind when diagnosing bipolar disorders) Medical conditions may present with prominent depressive Sx. If this is the case, then the disorder is diagnosed as secondary to it. Tx. usually involves treating the underlying general medical condition. Specific extrinsic factors such as drugs of abuse and medications could result in illness and are diagnosed also secondary to it. Tx. usually involves withdrawing or reducing the drug. Mania Vs. Schizo  a few features can help distinguish between the two: Personality and general functioning are usually satisfactory before and after a manic episode. delusions or hallucinations in manic patients can occur and typically reflect the underlying disturbance in mood (incongruent psychotic sx. occur occasionally and make the differentiation hard) family history of a mood disorder, a previous dx. mood disorder from which the patient completely or substantially recovered from. Bereavement - may have many depressive sx. for a sufficient duration to meet criteria for a depressive episode but diagnosis of depressive disorder is not given because the presence of the sx. Are considered a normal reaction. The Sx. Are usually self-limiting and clear up spontaneously over time. Bereavement usually does not respond to antidepressant medication.
  29. There is actually a lot of information on a bunch of these slides… I’m just going to point out some of the main treatments and important facts… for further information, if your interested, you can look it up in your PDR pages 266 to 269
  30. Second generation antipsychotics
  31. Mood stabilizer
  32. Mood stabilizer; inhibit GABA transaminase therefore increasing GABA (gamma aminobutyric acid  inhibitory) Pregnancy: spina bifida Valproate Syndrome: trigonocephaly, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, antiverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth
  33. Anticonvulsive and mood stabilizer; MOA stabilizes inactive form of sodium channels
  34. Ineffective in rapid-cycling Prophylaxis for bipolar I
  35. Can be used as maintenance on its own? And with a mood stabilizer Risk of depression has been reported
  36. With fluoxetine (Symbyax); indicated for bipolar disorder: depressive episode
  37. After a manic episode, the patient might need a maintenance dose to prevent subsequent relapses which he or she may need to take for several years or indefinitely the manic episode should be monitored closely because the patient may go into a depressive state as the manic episode comes to an end Sleep hygiene should also be discussed with the patient since there may have been a disruption during the manic episode Manic episodes can have devastating personal, social and economic consequences; that’ s why supportive psychotherapy should be considered to help them cope with those consequences and maintain their self-esteem As future clinicians, we need to keep these points in mind when assessing, diagnosing and treating patients with this illness. It is something we are going to see regularly, and knowing about and understanding bipolar disorders, even up to this level, will tremendously help in our own future practice.
  38. Van Gogh painting. He was though to suffer from bipolar disorder.