bipolar disorder
TRANSCRIPT
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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 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
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
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 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
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
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 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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