Bipolar DisorderOld diagnosis

Current problem

Future challenge

Bipolar disorder or manic-depressive

illness has been recognized since at least

the time of Hippocrates who described such

patients as amic and melancholicldquo

In 1899 Emil Kraepelin defined manic-

depressive illness and noted that persons

with manic-depressive illness lacked

deterioration and dementia which he

associated with schizophrenia

In 150 AD Aretaeus described mania and melancholia in the

same patient

Same physician who described and named diabetes

Kraepelin in 1913 formulated concept of ldquomanic depressive

insanityrdquo (which included recurrent affective disorders

Leonhard in 1957 elaborated concept of bipolarity

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Bipolar disorder or manic-depressive

illness has been recognized since at least

the time of Hippocrates who described such

patients as amic and melancholicldquo

In 1899 Emil Kraepelin defined manic-

depressive illness and noted that persons

with manic-depressive illness lacked

deterioration and dementia which he

associated with schizophrenia

In 150 AD Aretaeus described mania and melancholia in the

same patient

Same physician who described and named diabetes

Kraepelin in 1913 formulated concept of ldquomanic depressive

insanityrdquo (which included recurrent affective disorders

Leonhard in 1957 elaborated concept of bipolarity

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

In 150 AD Aretaeus described mania and melancholia in the

same patient

Same physician who described and named diabetes

Kraepelin in 1913 formulated concept of ldquomanic depressive

insanityrdquo (which included recurrent affective disorders

Leonhard in 1957 elaborated concept of bipolarity

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Kraepelin in 1913 formulated concept of ldquomanic depressive

insanityrdquo (which included recurrent affective disorders

Leonhard in 1957 elaborated concept of bipolarity

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Leonhard in 1957 elaborated concept of bipolarity

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Goodwin in early 1970rsquos described Bipolar II

Akiskal broadened concept of illness to Bipolar

Spectrum

Gorman and McCrank pointed out importance

of anxiety disorders

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

bull Common illness affecting 2 of the world population (5 if one includes spectrum disorders)

bull Consistently among 10 leading causes of medical disability in the world

bull 6th leading cause of medical disability in the developed nations

bull Prominent cognitive abnormalities

bull Particularly recalcitrant mental health problem

bull Symptomatic at least half the time

bull Can have impaired social function even when symptom-free

B

I

P

O

L

A

R

D

I

S

O

R

D

E

R

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

bull Depressed mood

bull Diminished interest or pleasure in all or almost all activities

bull Decreased or increased appetite

bull Significant weight loss or gain

bull Insomnia or hypersomnia

bull Psychomotor agitation or retardation

bull Fatigue or loss of energy

bull Feelings of worthlessness or excessive or inappropriate guilt

bull Diminished ability to think or concentrate

bull Recurrent thoughts of death

bull Recurrent suicidal ideation or attempts

Depressive Symptoms

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

bull Inflated self-esteem or grandiosity

bull Decreased need for sleep

bull More talkative than usual

bull Flight of ideas or subjective experience that thoughts are racing

bull Distractibility

bull Increase in goal-directed activity or psychomotor agitation

bull Excessive involvement in pleasurable activities that have a high potential for painful consequences

Manic Symptoms

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Bipolar Disorder and the Creative Genius

Thinking Outside the BoxMany famous historical figures gifted with creative talents may

have been affected by bipolar disorder Wolfgang Amadeus

Mozart Ludwig van Beethoven Virginia Woolf Isaac

Newton and Robert Schumann Salah Jaheen Almotanabee

Van Gogh are some people whose lives have been researched

to discover signs of mood disorder

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Mozartrsquos movements and behaviour a

case of Tourettersquos syndrome

Was Mozart Autistic Exploring the

Relationship Between Autism and

Creativity

Wolfgang Amadeus Mozart

1756-1791

Composer of over 600 musical works

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disorders

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

Wolfgang Amadeus Mozarts psychopathology

in light of the current conceptualization of

psychiatric disordersHuguelet P Perroud NDepartment of Psychiatry of Geneva Service de psychiatrie adulte 36 rue du XXXI Deacutecembre CH-1207

Geneva Switzerland philippehuguelethcugech

AbstractThe study of Mozarts letters and biography leads us to reconsider the

psychiatric disorders from which he suffered Indeed it seems that

Mozart demonstrated depressive episodes some of which were severe

and corresponded to the criteria of the DSM-IV classification However

the arguments put forward by other authors supporting the occurrence

of manic or hypomanic episodes (thus constituting a bipolar disorder

diagnosis) are not supported by sufficient historic proof Indeed the

length of time that the behaviors suggesting manic symptoms lasted is

not compatible with such a diagnosis Rather Mozarts mood swings

and impulsive behavior correspond to some traits of a personality

disorder that is for the most part symptoms of the dependent

personality disorder Evidence for this diagnosis appears most notably in

Mozarts reactions to his wifes absences but also in occasional

behaviors as well as mood lability The divergences in the classification

of Mozarts symptoms either into the field of bipolar disorders or into

that of personality disorders are closely linked to the nosological

uncertainties that are still a source of debate in todays psychiatric

research We discuss a means of overcoming this limitation by

considering the concept of soft bipolar spectrum a

conceptualization that corresponds to Mozarts psychiatric history

DSM-IV-TR

Classification of Bipolar Disorders

Symptoms do not meet criteria for manic and depressive episodes

Bipolar features

that do not meet

criteria for any

specific bipolar

disorders

At least 2 years of

numerous periods

of hypomanic and

depressive

symptoms

One or more

major depressive

episodes

accompanied

by at least one

hypomanic

episode

FEMALEgtMALE

One or more

manic or mixed

episodes usually

accompanied by

major depressive

episodes

MALE=FEMALE

Bipolar Disorder

Not Otherwise

SpecifiedCyclothymicBipolar IIBipolar I

First ed Diagnostic and Statistical Manual of Mental Disorders 4th ed Text Rev

Washington DC American Psychiatric Association 2000345-428

Manic episode 1 week

Hypomnic episode 4 days

Depressive Episode 2 weeks

Mixed episode 1 week

Cyclothymia 2 years

Manic episode 1 week

Hypomnic episode 4 days

Depressive Episode 2 weeks

Mixed episode 1 week

Cyclothymia 2 years

Akiskals Schema of Bipolar Subtypes

(Psychiatric Clinics of North America 223 September 1999 Medscape Family

Medicine 20057[1])

Bipolar I full-blown mania

Bipolar I frac12 depression with protracted hypomania

Bipolar II depression with hypomanic episodes

Bipolar II frac12 cyclothymic disorder

Bipolar III hypomania due to antidepressant drugs

Bipolar III frac12 hypomania andor depression associated with

substance use

Bipolar IV depression associated with hyperthymic temperament

Bipolar V recurrent depressions that are admixed with dysphoric

hypomania

Bipolar VI late onset depression with mixed mood features

progressing to a dementia-like syndrome

bull MortalityMorbidity

Bipolar disorder has significant morbidity and mortality rates

Approximately 25-50 of individuals with bipolar disorder attempt suicide

and 11 actually commit suicide

bull Race

No racial predilection exists

bull Sex

Bipolar I disorder occurs equally in both sexes

rapid-cycling bipolar disorder (4 or more episodes a year) is more common

in women than in men

Incidence of bipolar II disorder is higher in females than in males

bull Age

The age of onset of bipolar disorder varies greatly

The age range for both bipolar I and bipolar II is from childhood to 50

years with a mean age of approximately 21 years(15-19 years)(20-24

years)

Onset of mania in people older than 50 years should lead to an

investigation for medical or neurologic disorders such as cerebrovascular

disease

Epidemiology

Bipolar Disorder challenges

Bipolar disorder has a number of contributing factors

including genetic biochemical psychodynamic and

environmental elements

Evidence is mounting of the contribution of glutamate to both bipolar and major depressions A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased

catecholamine hypothesis which holds that an increase in epinephrine

and norepinephrine causes mania and a decrease in epinephrine and norepinephrine

causes depression

Hormonal imbalances and disruptions of the hypothalamic-pituitary-

adrenal axis involved in homeostasis and the stress response may also contribute to

the clinical picture of bipolar disorder

Biochemical causes

Psychodynamic mania serves as a defense against the feelings of

depression

Environmentalexternal stresses or the external pressures may serve to

exacerbate some underlying genetic or biochemical

predisposition

Pregnancy is a particular stress for women with a manic-

depressive illness history and increases the possibility of

postpartum psychosis

bull Structural and Functional Brain Abnormalities

ndash amygdala anterior cingulate and prefrontal cortex putamen thalamushypothalamus

bull Highly heritable (80 genetic contribution)

ndash Multiple genes

ndash 16 different chromosomal regions

Bipolar Disorder

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

bull MortalityMorbidity

Bipolar disorder has significant morbidity and mortality rates

Approximately 25-50 of individuals with bipolar disorder attempt suicide

and 11 actually commit suicide

bull Race

No racial predilection exists

bull Sex

Bipolar I disorder occurs equally in both sexes

rapid-cycling bipolar disorder (4 or more episodes a year) is more common

in women than in men

Incidence of bipolar II disorder is higher in females than in males

bull Age

The age of onset of bipolar disorder varies greatly

The age range for both bipolar I and bipolar II is from childhood to 50

years with a mean age of approximately 21 years(15-19 years)(20-24

years)

Onset of mania in people older than 50 years should lead to an

investigation for medical or neurologic disorders such as cerebrovascular

disease

Epidemiology

Bipolar Disorder challenges

Bipolar disorder has a number of contributing factors

including genetic biochemical psychodynamic and

environmental elements

Evidence is mounting of the contribution of glutamate to both bipolar and major depressions A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased

catecholamine hypothesis which holds that an increase in epinephrine

and norepinephrine causes mania and a decrease in epinephrine and norepinephrine

causes depression

Hormonal imbalances and disruptions of the hypothalamic-pituitary-

adrenal axis involved in homeostasis and the stress response may also contribute to

the clinical picture of bipolar disorder

Biochemical causes

Psychodynamic mania serves as a defense against the feelings of

depression

Environmentalexternal stresses or the external pressures may serve to

exacerbate some underlying genetic or biochemical

predisposition

Pregnancy is a particular stress for women with a manic-

depressive illness history and increases the possibility of

postpartum psychosis

bull Structural and Functional Brain Abnormalities

ndash amygdala anterior cingulate and prefrontal cortex putamen thalamushypothalamus

bull Highly heritable (80 genetic contribution)

ndash Multiple genes

ndash 16 different chromosomal regions

Bipolar Disorder

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Bipolar Disorder challenges

Bipolar disorder has a number of contributing factors

including genetic biochemical psychodynamic and

environmental elements

Evidence is mounting of the contribution of glutamate to both bipolar and major depressions A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased

catecholamine hypothesis which holds that an increase in epinephrine

and norepinephrine causes mania and a decrease in epinephrine and norepinephrine

causes depression

Hormonal imbalances and disruptions of the hypothalamic-pituitary-

adrenal axis involved in homeostasis and the stress response may also contribute to

the clinical picture of bipolar disorder

Biochemical causes

Psychodynamic mania serves as a defense against the feelings of

depression

Environmentalexternal stresses or the external pressures may serve to

exacerbate some underlying genetic or biochemical

predisposition

Pregnancy is a particular stress for women with a manic-

depressive illness history and increases the possibility of

postpartum psychosis

bull Structural and Functional Brain Abnormalities

ndash amygdala anterior cingulate and prefrontal cortex putamen thalamushypothalamus

bull Highly heritable (80 genetic contribution)

ndash Multiple genes

ndash 16 different chromosomal regions

Bipolar Disorder

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Bipolar disorder has a number of contributing factors

including genetic biochemical psychodynamic and

environmental elements

Evidence is mounting of the contribution of glutamate to both bipolar and major depressions A postmortem study of the frontal lobes with both these disorders revealed that the glutamate levels were increased

catecholamine hypothesis which holds that an increase in epinephrine

and norepinephrine causes mania and a decrease in epinephrine and norepinephrine

causes depression

Hormonal imbalances and disruptions of the hypothalamic-pituitary-

adrenal axis involved in homeostasis and the stress response may also contribute to

the clinical picture of bipolar disorder

Biochemical causes

Psychodynamic mania serves as a defense against the feelings of

depression

Environmentalexternal stresses or the external pressures may serve to

exacerbate some underlying genetic or biochemical

predisposition

Pregnancy is a particular stress for women with a manic-

depressive illness history and increases the possibility of

postpartum psychosis

bull Structural and Functional Brain Abnormalities

ndash amygdala anterior cingulate and prefrontal cortex putamen thalamushypothalamus

bull Highly heritable (80 genetic contribution)

ndash Multiple genes

ndash 16 different chromosomal regions

Bipolar Disorder

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

bull Structural and Functional Brain Abnormalities

ndash amygdala anterior cingulate and prefrontal cortex putamen thalamushypothalamus

bull Highly heritable (80 genetic contribution)

ndash Multiple genes

ndash 16 different chromosomal regions

Bipolar Disorder

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Pathophysiology

bull Two particular genes ANK3 (ankyrinG) and CACNA1C (alpha 1C subunit of the L-type voltage-gated calcium channel)

bull ANK3 is an adaptor protein found at axon initial segments that regulates the assembly of voltage-gated sodium channels and both ANK3 and subunits of the calcium channel are down-regulated in mouse brain in response to lithium indicating a possible therapeutic mechanism of action of one of the most effective treatments for bipolar disorder

bull 80 genetic contributionndash Complex genetic disorder multiple different

common disease allelesndash 16 different chromosomal regions

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Pathophysiologybull Diacylglycerol kinase eta (DGKH) gene DGKH is a key protein in the

lithium-sensitive phosphatidyl inositol pathway

bull Glycogen Synthase Kinase 3-beta (GSK3β) Lithium-mediated inhibition of GSK3β is thought to result in down-regulation of molecules involved in cell death and upregulation of neuroprotectivefactors

bull GSK3β is a central regulator of the circadian clock and lithium-mediated modulation of circadian periodicity is thought to be a critical component of its therapeutic effect

bull COMT gene (Catechol-O-methyltransferase ) has important role in Intelligence BP schizophrenia

bull CLOCK gene(Circadian Locomotor Output Cycles Kaput ) a dominant-negative mutation in the CLOCK gene normally contributing to circadian periodicity in humans results in manic-like behavior in mice

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Pathophysiology

bull Manic behavior in CLOCK mutant mice includes hyperactivity decreased sleep reduced anxiety

and an increased response to cocainerarrrarrprovides a shared biological basis for the high rate of substance abuse observed in clinical populations of subjects with bipolar disorder

bull Experimenters were able to abolish the manic behaviors by rescuing expression of normal CLOCK specifically in the ventral tegmental area of the mouse brain This area is rich in D2 receptors

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Pathophysiologybull Oligodendrocyte-myelin-related genes

appear to be decreased in brain tissue from

persons with bipolar disorder

bull loss of myelin is thought to disrupt

communication between neurons leading to

some of the thought disturbances observed

in bipolar disorder and related illnesses

bull Brain imaging studies of persons with bipolar

disorder also show abnormal myelination in

several brain regions associated with this

illness

Gene expression and neuroimaging mood disorders and

schizophrenia may share some biological underpinnings possibly

related to psychosis

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

bull Lithium and Valproate effect up-regulation of Cytoprotectiveprotein Bcl-2 in the frontal cortex and the hippocampus

bull Neuro-imaging studies suggest evidence of cell loss or atrophy in these same brain regions in bipolar and mood disorders patients Thus another suggested cause of bipolar disorder is damage to cells in the critical brain circuitry that regulates emotion

bull According to this hypothesis mood stabilizers and antidepressants are thought to alter mood by stimulating cell survival pathways and increasing levels of neurotrophic factors to improve cellular resiliency

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Bipolar disorder and Schizophrenia

bull Bipolar disorder and schizophrenia share common

susceptibility genes on chromosome 6

bull These genes are located in a section of the

chromosome containing genes involved in immunity

and controlling how and when genes turn on and off

This connection can help explain the

link between environmental stress and

schizophrenia and possibly bipolar

disorder

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Bipolar disorder and Schizophrenia

Bipolar Disorder Shared Genes Schizophrenia

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Mental Illness

amp

Genetics

Schizophrenia Bipolar Disorder

Alzheimerrsquos Disease

Depression

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Mental Illness amp Genetics

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Evidence-based markers of Bipolar Disorder

bull The patient has had repeated episodes of major depression (four or more seasonal shifts in mood are also common)

bull The first episode of major depression occurred before age 25 (some experts say before age 20 a few before age 18 most likely the younger you were at the first episode the more it is that bipolar disorder not unipolar was the basis for that episode)

bull A first-degree relative (motherfather brothersister daughterson) has a diagnosis of bipolar disorder

bull When not depressed mood and energy are a bit higher than average all the time (hyperthymic personality)

bull When depressed symptoms are atypical extremely low energy and activity excessive sleep (eg more than 10 hours a day) mood is highly reactive to the actions and actions of others and (the weakest such sign) appetite is more likely to be increased than decreased Some experts think that carbohydrate craving and night eating are variants of this appetite effect

bull Episodes of major depression are brief eg less than 3 months

bull The patient has had psychosis (loss of contact with reality) during an episode of depression

bull The patient has had severe depression after giving birth to a child (postpartum depression)

bull The patient has had hypomania or mania while taking an antidepressant (remember severe irritability difficulty sleeping and agitation may -- but do not always -- qualify for hypomania)

bull The patient has had loss of response to an antidepressant (sometimes called Prozac Poop-out) it worked well for a while then the depression symptoms came back usually within a few months

bull Three or more antidepressants have been tried and none worked

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

ANXIOUS DEPRESSION

COULD BE BIPOLAR

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Anxiety Disorders Posttraumatic Stress Disorder

Cushing Syndrome Schizoaffective Disorder

Head Trauma Schizophrenia

Hyperthyroidism Systemic Lupus Erythematosus

Hypothyroidism

Other Problems to Be ConsideredbullCancer

bullNeurosyphilis

bullEpilepsy (See the Medscape Epilepsy Resource Center)

bullFahr disease

bullAIDS

bullMultiple sclerosis

bullMedications (eg antidepressants can propel a patient into mania other medications may include

baclofen bromide bromocriptine captopril cimetidine corticosteroids cyclosporine disulfiram

hydralazine isoniazid levodopa methylphenidate metrizamide procarbazine procyclidine)

bullCircadian rhythm desynchronization

bullAttention deficit hyperactivity disorder (ADHD) especially in children and adolescents

bullCyclothymic disorder

bullMultiple personality disorder

bullOppositional defiant disorder (in children)

bullSubstance abuse disorders (eg with alcohol amphetamines cocaine hallucinogens opiates)

Differential Diagnoses

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Medical Care

Inpatient hospital treatmentThe indications for hospitalization in a person with bipolar disorder include the

following

bullDanger to self

bullDanger to others

bullTotal inability to function

bullMedical conditions that warrant medication monitoring

Partial hospitalization or a day-treatment programIn general these patients have severe symptoms but have a level of control and a

stable living environment

Outpatient treatment has 4 major goals

1 First look at areas of stress and find ways to handle them This is a form of

psychotherapy

2 Second monitor and support the medication

3 Third develop and maintain the therapeutic alliance

4 The fourth aspect involves education

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Evidence-based guidelines

for treating

bipolar disorder

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

Medication Why you might choose it

lamotrigineLamictalbullDepression is the dominant symptom Rapid cycling Need all the antidepressant you can get

Afraid of weight gain

lithiumbullClassic bipolar I symptom pattern euphoric mania and severe depressions Significant manic

symptoms Need all the antidepressant you can get Suicide risk is a concern Very inexpensive

quetiapineSeroquelbullDepression and agitation are both severe Severe sleep problems Anxiety is a significant symptom

No family history of diabetes

divalproexDepakotebullNeed something strong and fast Male and not afraid of weight gain Rapid cycling Significant manic

symptoms

carbamazepineTegretolbullRapid cycling Severe sleep problems Cant take Depakote (eg afraid of weight gain risk) Cant

afford Trileptal or need the stronger option

olanzapineZyprexabullEmergency-level symptoms Need help really fast Can use on as-needed basis (If you continue to

use it regularly) Not afraid of weight gain

oxcarbazepineTrileptalbullMilder symptoms can risk a possibly weaker agent Significant manic symptoms Alternative to

Depakote as a starting place Low long-term risk is appealing

omega-3 fatty acids

fish oil

bullNatural biggest known risk is seal burps Milder symptoms can risk a weaker agent You want to

add a possible mood stabilizer without adding more medicationldquo Depression is a major symptom

bullWilling to take a lot of pills or swallow (flavored) fish oil

verapamilbullPossible alternative for pregnancy Low side effect risk

bullTried many other medications but not ready for clozapine

clozapinebullTried everything else Severe symptoms Ready for major weight gain weekly blood tests Ready

for one of the most effective medications we have

atypical (2nd

generation)

antipsychotics

bullLow-dose boosters for specific problems (as add-ons to real mood stabilizers) Seroquel for sleep

and agitation has weight gain risk

bullrisperidone for elderly at very low doses or BPI perhaps -- tricky antidepressant effects in some

bullGeodon no clear role but hey it causes less weight gain than Zyprexa and really helps an

occasional patient

bullAbilify strong antimanic not so clear regarding depression -- but still learning about this one (as of

12009)

12152014

12152014