BIPOLAR DISORDER

Summary Pathophysiology
Bipolar I Disorder is one of the most The pathophysiology of Bipolar I Disorder
severe forms of mental illness and is is poorly understood. However, a variety
characterized by recurrent episodes of of imaging studies suggests the
mania and (more often) depression. The involvement of structural abnormalities in
condition has a high rate of recurrence and the amygdala, basal ganglia and prefrontal
if untreated, it has an approximately 15% cortex. Research is now showing that this
risk of death by suicide. It is the third disorder is associated with abnormal brain
leading cause of death among people aged levels of serotonin, norepinephrine, and
15-24 years, and is the 6th leading cause of dopamine.
disability (lost years of healthy life) for Prevalence
people aged 15-44 years in the developed
world. Bipolar I Disorder affects both sexes
equally in all age groups and its worldwide
Causation prevalence is approximately 3-5%. It can
Bipolar I Disorder is a life-long disease even present in preschoolers. There are no
and runs in families but has a complex significant differences among racial groups
mode of inheritance. Family, twin and in the prevalence of this disorder.
adoption studies suggest genetic factors. Course
The concordance rate for monozygotic
(identical) twins is 43%; whereas it is The first episode may occur at any age
only 6% for dizygotic (nonidentical) twins. from childhood to old age. The average
About half of all patients with Bipolar I age at onset is 21. More than 90% of
Disorder have one parent who also has a individuals who have a single Manic
mood disorder, usually Major Depressive Episode go on to have future episodes.
Disorder. If one parent has Bipolar I Untreated patients with Bipolar I Disorder
Disorder, the child will have a 25% chance typically have 8 to 10 episodes of mania
of developing a mood disorder (about half and depression in their lifetime. Often 5
of these will have Bipolar I or II Disorder, years or more may elapse between the first
while the other half will have Major and second episode, but thereafter the
Depressive Disorder). If both parents have episodes become more frequent and more
Bipolar I Disorder, the child has a 50%- severe.
75% chance of developing a mood There is significant symptom reduction
disorder. First-degree biological relatives between episodes, but 25% of patients
of individuals with Bipolar I Disorder have continue to display mood instability or
elevated rates of Bipolar I Disorder (4%- mild depression. As many as 60% of
24%), Bipolar II Disorder (1%-5%), and patients experience chronic interpersonal
Major Depressive Disorder (4%-24%). or occupational difficulties between acute
The finding that the concordance rate for episodes. Bipolar I Disorder may develop
monozygotic twins isn't 100% suggests psychotic symptoms. The psychotic
that environmental or psychological symptoms in Bipolar I
factors likely play a role in causation. Disorderonly occur during severe manic,
Certain environmental factors (e.g., mixed or depressive episodes. In contrast,
antidepressant medication, antipsychotic the psychotic symptoms in Schizophrenia
medication, electroconvulsive therapy, can occur when there is no mania or
stimulants) or certain illnesses (e.g., depression. Poor recovery is more
multiple sclerosis, brain tumor, common after psychosis.
hyperthyroidism) can trigger mania. Mania
Manic episodes usually begin abruptly and
can be triggered by giving birth, sleep
last for between 2 weeks and 4-5 months
deprivation, and major stressful life events.
(median duration about 4 months).
Symptoms Depressive episodes tend to last longer
In adults, mania is usually episodic with an (median length about 6 months), though
elevation of mood and increased energy rarely for more than a year, except in the
and activity. In children, mania is elderly.
commonly chronic rather than episodic, Treatment And Outcome
and usually presents in mixed states with
The usual treatment for Bipolar I Disorder
irritability, anxiety and depression. In
is lifelong therapy with a mood-stabilizer
adults and children, during depression
(either lithium, carbamazepine, or
there is lowering of mood and decreased
divalproex / valproic acid) often in
energy and activity. During a mixed
combination with an antipsychotic
episode both mania and depression can
medication. Usually treatment results in a
occur on the same day.
dramatic decrease in suffering, and causes
Comorbidity an 8-fold reduction in suicide risk. In
Comorbidity is the rule, not the exception, mania, an antipsychotic medication and/or
in bipolar disorder. The most common a benzodiazepine medication is often
mental disorders that co-occur with bipolar added to the mood-stabilizer. In
disorder are anxiety, substance use, and depression, quetiapine, olanzapine, or
conduct disorders. Disorders of eating, lamotrigine is often added to the mood-
sexual behavior, attention- stabilizer. Alternatively, in depression, the
deficit/hyperactivity, and impulse control, mood-stabilizer can be switched to another
as well as autism spectrum disorders and mood-stabilizer, or two mood-stabilizers
Tourette's disorder, co-occur with bipolar can be used together. Sometimes, in
disorder. The most common general depression, antidepressant medication is
medical comorbidities are migraine, used. Since antidepressant medication can
thyroid illness, obesity, type II diabetes, trigger mania, antidepressant medication
and cardiovascular disease. should always be combined with a mood-
stablizer or antipsychotic medication to
Associated Mental Disorders
prevent mania.
Bipolar I Disorder is often associated with:
alcoholism, drug addiction, Anorexia Research has shown that the most effective
Nervosa, Bulimia Nervosa, Attention- treatment is a combination of supportive
Deficit Hyperactivity Disorder, Panic psychotherapy, psychoeducation, and the
Disorder, and Social Phobia. use of a mood-stabilizer (often combined
with an antipsychotic medication). There is
Diagnostic Tests
no research showing that any form of
There are no diagnostic laboratory tests for psychotherapy is an effective substitute for
Bipolar I Disorder. Thus diagnosis is medication. Likewise there is no research
arrived at by using standardized diagnostic showing that any "health food store
criteria to rate the patient's behavior. Onset nutritional supplement" (e.g., vitamin,
of mania after age 40 could signify that the amino acid) is effective for Bipolar I
mania may be due to a general medical Disorder.
condition or substance use. Current or past
Since a Manic Episode can quickly
hypothyroidism (or even mild thyroid
escalate and destroy a patient's career or
hypofunction) may be associated with
reputation, a therapist must be prepared to
Rapid Cycling. Hyperthyroidism may
hospitalize out-of-control manic patients
precipitate or worsen mania in individuals
before they "lose everything". Likewise,
with a preexisting Mood Disorder.
severely depressed, suicidal bipolar
However, hyperthyroidism in individuals
patients often require hospitalization to
without preexisting Mood Disorder does
save their lives.
not typically cause manic symptoms.
Differential Diagnosis Although the medication therapy for
Bipolar I Disorder usually must be
Bipolar I Disorder must be distinguished
lifelong, the majority of bipolar patients
from:
are noncompliant and stop their medication
• Mood Disorder Due to a General after one year. At 4-year follow-up of
Medical Condition (e.g., due to bipolar patients, 41% have a good overall
multiple sclerosis, stroke, outcome and 4% have died. Women with
hypothyroidism, or brain tumor) bipolar disorder lose, on average, 9 years
in life expectancy, 14 years of lost
• Substance-Induced Mood Disorder productivity and 12 years of normal health
(e.g., due to drug abuse,
antidepressant medication, or Best Recoveries
electroconvulsive therapy) The best recoveries are achieved when
individuals with Bipolar I Disorder:
• Other Mood Disorders (e.g., Major
Depressive Disorder; Dysthymia; 1. Get the correct diagnosis
Bipolar II Disorder; Cyclothymic (since many are misdiagnosed as
Disorder) having schizophrenia or "just
borderline personality")
• Psychotic Disorders (e.g.,
Schizoaffective Disorder, 2. Get effective treatment and
Schizophrenia, or Delusional faithfully stay on it for a lifetime
Disorder) (most individuals require the
combination of a mood-stabilizer
• Since this disorder may be
plus an antipsychotic medication)
associated with hyperactivity,
recklessness, impulsivity, and 3. Adopt a healthy lifestyle
antisocial behavior; the diagnosis of (regular sleep and exercise; no
Bipolar I Disorder must be carefully alcohol or drug abuse; low stress)
differentiated from Attention Deficit
4. Regularly see a supportive
Hyperactivity Disorder, Conduct
physician who is knowledgeable
Disorder, Antisocial Personality
about the psychiatric management
 Disorder, and Borderline Personality
Disorder
TREATMENT
Depressive Episode
Proven (Better Than Placebo) Treatments Proven (Better Than Placebo) Treatments
for Bipolar Depression
• Lithium and anticonvulsants
prevent suicide [ 1, 2,3, 4 ]
• Lithium (for prevention of future
depression andsuicide)
• Carbamazepine (for prevention of
future depression)
• Lamotrigine (for depression)
• Olanzapine (for suicidal ideation in
bipolar I manic or mixed-episode
patients)
• Quetiapine (for depression)
• Fluoxetine (for depression)
• Imipramine (for depression but
not prevention of future depression)
• Tranylcypromine (for depression)
of this disorder
5. Learn which symptoms
predict the return of this illness,
and what additional "rescue"
medication should be taken
6. Learn to trust the warnings
given by family and friends when
they see early signs of relapse
7. Learn as much as possible
about this illness from therapists,
the Internet, books, or self-help
groups
Manic Episode
for Mania
• Monotherapy (treatment with just
one medication) for Bipolar Disorder is
usually inadequate, and most patients
require a combination of a mood-
stabilizer and antipsychotic medication
• Lithium (for mania & prevention of
future mania(59% success rate), but
increases risk of diabetes
insipidus and hypothyroidism)
• Carbamazepine
(for mania & prevention of future
mania)
• Divalproex sodium (for mania but
not prevention of future mania, but
increases risk of polycystic
ovaries and hyperinsulinemia)
• No difference between in generic
valproic acid and divalproex sodium in
hospitalization
• Olanzapine (for mania but increases
 risk of weight gain & diabetes)
• Olanzapine (for suicidal ideation in
bipolar I manic or mixed episodes)
• Quetiapine (for mania)
• Risperidone (for mania)
• Haloperidol (for mania)

• Caution: is the increased use

of atypical antipsychotic
medication (e.g., olanzapine) causing
an increased risk of stroke, heart
disease and hypertension?
Promising (But Unproven) Treatments for Promising (But Unproven) Treatments for
Bipolar Depression Mania

• Amitriptyline (with mood- • Clozapine (but increases risk

stabilizer) of diabetes andagranulocytosis)
• Cognitive Therapy (with mood- • Electroconvulsive Therapy
stabilizer) • Lamotrigine (for prevention of
• Electroconvulsive Therapy (no future rapid-cycling)
placebo-controlled trials)
• Family Psychoeducation (with • Phenytoin (with neuroleptic for
mood-stabilizer) mania}
• Group Psychoeducation (with
mood-stabilizer)
• L-Sulpiride (with mood-stabilizer)
• Moclobemide (with mood-
stabilizer)
• Paroxetine (with mood-stabilizer)
• Psychotherapy (with mood-
stabilizer)

• Venlafaxine (with mood-stabilizer)

Ineffective Treatments for Depression Ineffective Treatments for Mania

• No additional benefit of adding • Gabapentin

antidepressant medication to a mood • Verapamil
stabilizer
• Topiramate
• Do certain medications for Bipolar monotherapy or adjunctive therapy
Disorder increase suicidal risk? with Topiramate (and has serious side-
[ 1, 2, 3, 4, 5, 6, 7 ] effects)
Illness Course for Depression Illness Course for Mania
 • Bipolar Disorder and severe Major
Depressive Disorder are episodic, life-
long illnesses that need life-long
prophylactic treatment
• Untreated depressive episodes
usually last 11 weeks
• Usually there are multiple
episodes of depression if untreated
• Suicide rate for bipolar patients
is 15-22 times the national average
• Suicide rate in first year off lithium
therapy is 20 times the rate when on
lithium
http://www.mentalhealth.com/dis/p20-md02.html
• Untreated pure manic episodes
usually last 6 weeks
• Untreated mixed
(manic+depressive) episodes usually
last 17 weeks
• Usually there are multiple
episodes of mania if untreated
• Mania usually returns 5
months after stopping lithium therapy
• Within 2-4 years of first lifetime
hospitalization for mania, 43%
achieved functional recovery, and 57%
switched or had new illness episodes