Learning Objectives:

1. The physician will be able to

recognize/distinguish bipolar/manic

symptoms from other symptoms of mental

illness.

2. The physician will be able to initiate

treatment and monitor for complications.

3. The physician will be able to avoid pitfalls for

treatment of general medical conditions to

prevent a manic episode from occurring in

individuals susceptible to a manic episode.

What is Bipolar Disorder?

A severe mental illness characterized by

symptoms of at least one manic or hypomanic

episode and may or may not be associated with

having a depressive episode in a person’s

lifetime. It is cyclical in nature and progressive.1

Bipolar and Related Disorders

The Diagnostic and Statistical Manual of

Mental Disorders has sandwiched Bipolar

related disorders between the Schizophrenia

Spectrum disorders and Depressive

disorders to recognize the relationship

between these disorders. 1

The Big Three

For today’s purposes, we are going to focus

on Bipolar I and Bipolar II disorder with

mention of Cyclothymia.

What is the difference?

In a nutshell, to meet criteria for Bipolar I

disorder, your patient has had to have met

the criteria for at least one Manic episode in

his or her lifetime. That episode should

have been severe enough to warrant

hospitalization or to cause significant

impairment in functioning (this can include

incarceration). 1

What is the difference?

In the Bipolar II patient, you must have met

criteria for a hypomanic episode, and while

impairment in level of functioning is

impaired, it is less severe than that of the

Bipolar I patient. In addition, the Bipolar II

patient has had to have had a depressive

episode in his or her lifetime.1

What is the difference?

In the Cyclothymic patient, he or she has

experienced manic episodes without ever

having had a depressive episode. 1

What is Mania?

http://www.cornel1801.com/disney/Adventur

es-Ichabod-Toad-1949/film1.html

Manic vs. Hypomanic

The difference between the two are time and

severity.

For the “A” criteria of a manic episode, the

symptoms last at least a week or

hospitalization is necessary.1

Manic vs. Hypomanic

For the “A” criteria in the hypomanic

episode, the symptoms last at least four

consecutive days, change in functioning is

noticeable by others, but not severe enough

to cause major impairments. 1

The “A” Criteria

The patient has a “distinct period and

persistently elevated, expansive, or irritable

mood

AND

persitently increased goal-directed activity or

energy”1

What does that look like?

Elevated and Expansive

Irritable

Children and Adolescents

Irritable and destructive

Depressive episode tends to have physical

complaints. 2

Goal-Directed Activity

Taking on of more new projects or

commitments than normally, because pesky

things like sleep or common sense would

stand in his or her way.

The “B” Criteria

During this episode of abnormal mood and

activity/energy, one must also have at least

three (four if mood is only irritable) of the

following seven criteria.1

1. Self-Esteem

The self-esteem is inflated or grandiose.

They can be benign expansions of the truth

or floridly reaching delusional levels.

Example of inflated self-esteem:

In meeting with Mr. Jones to see what he’d like to work on,

he at first presented humbley with “small” body language.

As our discussion pregressed, his eye contact frequency

increased, body language enlarged and he became more

boastful about his education. He was proud of his

education and boasted of having learned Algebra,

Calculus, Trigonometry, Cosmology, Physics and

Psychology, but neglected to mention that he had only

earned his GED. He would like to try phase groups, but he

felt isolated by his intelligence and stated that he was

educationally baffling even to psychologists.

2. Decreased Need for Sleep

Feels rested after only a few hours

3. Speech

More talkative than usual

or

pressured to keep talking.

Warning: What is cultural?

4. Flight of Ideas

Racing Thoughts

The Patient’s train of thought is

characterized by shifting from one topic to

another. There may be some connection

between ideas, albeit tenuous, but may be

understandable.

When moderate to severe, it can be

elevated to illogical.

What does that look like?

“The sky is blue. Blue is my favorite color.

My mom took me to Color-Me-Mine once. I

painted a mug. Don’t drive through Los

Angeles; you’ll get mugged.”

What does it look like?

Patient: I came to see you to the psychiatrist’s office

because you have the time to listen to me GPs don’t have

the time to listen to me because he’s not very clever he

takes some interest in me sometimes but sometimes he

doesn’t I’ve got real important stuff to show you because

there is real important stuff here.

Psychiatrist: What is your name?

Patient: Names? Names are games, diddley dang

whatsyourname? (laughing)

What does it look like?

Often times the patient may tell you that his

or her thoughts are racing and like the

previous example, that is evident.

Sometimes the patients thoughts are so

rapid that he or she can’t keep up with the

thoughts and may have trouble himself

being able to express any thoughts.

5. Distractibility

Attention is too easily drawn to unimportant

or irrelevant external stimuli.

6. Increase in Goal Directed

Activity/Energy

If the patient is only experiencing a

hypomanic episode, this can be

advantageous to his or her career.

6. or Psychomotor agitation

Purposeless non-goal-directed activity. It

can also be manifested by pacing, hand

wringing or picking at the patient’s nails,

hair, etc.

7. Excessive involvement in

activities that have a high

potential for painful

consequences

Engaging in unrestrained buying

sprees

Sexual Indiscretions

Foolish Business

Investments

Test Film

https://www.youtube.com/watch?v=wuk8AOj

GURE

Test Question

1. In the film, Good Morning Vietnam, in this

scene, Robin Williams’ character

demonstrates which of the following

manic symptoms?

a. racing thoughts

b. pressured speech

c. elevated and expansive mood

d. All of the above

What it isn’t

Not secondary to a substance.

Not due to a general medical condition.

It is not better explained by another major

psychiatric disorder.

Is it mania? Or is it meth?

Methamphetamines, amphetamines,

cocaine, and PCP can all give manic like

presentations.

Prescription Medications that

Induce Manic Symptoms

All Antidepressant medications have been

implicated in inducing manic-like or manic

episodes. 3,4

L-Dopa, Corticosteroids, Anabolic-

androgenic steroids 3

Tramadol 5

Isoniazide 6

Clarithromycin, Ciprofloxacin and Ofloxacin

among other antimicrobials 6

Thyroid Induced Mania

Either by supplementation or by Grave’s

Disease itself can induce a manic-like

episode or exacerbate mania. 7,8

Borderline Personality Disorder

“Mood Swings” is NOT bipolar disorder.

If her mood is like the weather and not the

season, she could be a borderline.

Demi Lovato on Her Bipolar

Disorder: “It's a Daily Thing”Lovato tells Cosmopolitan for

Latinas, which named her its "Fun,

Fearless Latina of the Year." 9,10

At 21, Lovato has overcome many hurdles –

including an eating disorder, drug abuse, self-

mutilation, rehab and a nervous breakdown –

but the pop singer remains open about her

struggles, hoping to inspire others, especially

young people. 10

I Hate You, Don’t Leave Me

I hate you, don’t leave me

I feel like I can’t breathe

Just hold me, don’t touch me

And I want you to love me

But I need you to trust me

Stay with me, set me free

But I can’t back down, no, I can’t deny

That I’m staying now ’cause I can’t decide

Confused and scared I am terrified of you

I admit, I’m in and out of my head

Don’t listen to a single word I’ve said

Just hear me out before you run away

‘Cause I can’t take this pain

I hate you, don’t leave me

I hate you, don’t leave me

‘Cause I love when you kiss me

I’m in pieces, you complete me

But I can’t back down, no, I can’t deny

That I’m staying now ’cause I can’t decide

Confused and scared I am terrified of you

I admit, I’m in and out of my head

Don’t listen to a single word I’ve said

Just hear me out before you run away

‘Cause I can’t take this pain

No

I’m addicted to the madness

I’m a daughter of the sadness

I’ve been here too many times before

I’ve been abandoned and I’m scared now

I can’t handle another fall out

I am fragile, just washed up on the shore

They forget me, don’t see me

When they love me, they leave me

I admit, I’m in and out of my head

Don’t listen to a single word I’ve said

Just hear me out before you run away

‘Cause I can’t take this pain

No, I can’t take this pain

I hate you, don’t leave me

I hate you, please, love me11

STIGMA

Take a break?

12

12

Demographics

In bipolar illness, Men and women are

equal...but not really.13

Demographics

Bipolar disorder is an equal opportunity

illness. It does not discriminate.

Demographics

Economic factors

#6

$45 Billion 14,15,16

Comorbidities

Most Common

Psychiatric Disorders

Anxiety

Substance Use

disorders (Alcohol and

Cannabis) 18

Conduct Disorders

Most Common General

Medical Conditions

Migraine

Thyroid disorders

Obesity

Type II Diabetes

Cardiovascular

Disease19

Mortality

Women 9.0 years

Men 8.5 years

than the general population.

All Cause 2-fold greater 21

Mortality

Cardiovascular disease

Diabetes mellitus

COPD

Influenza/pneumonia

Unintentional injuries

Suicide

Cancer for women only 21

Mortality

Don’t blame it on the medications.

No treatment increases mortality.20

Mortality

Access

Unhealthy lifestyle factors

Smoking

Substances

Obesity20

Mortality

Suicide

Women 10 fold

Men 8 fold

1 in 5 Completes 21

Mortality Due to Suicide

Risk Factors

Prior Suicide Attempt

Degree of which the patient rates the

severity of the acute illness 22,23

Cigarette Smoking 23

Mortality Due to Suicide

Lithium is better than Depakote 24

Patients are at highest risk for suicide when

stopping or lowering Lithium. 25

Causality

?

Causality

Genetics

Heritability overall is about 60%

Risk to offspring is 27% for one parent and

50-65% in both for bipolar and up to 75% for

any affective disorder.

Second degree relatives 5%25

Causality

Genetics

No single gene

226 Empirically significant genes

6 Neurological Pathways 25

Causality

Head Injury

28% more likely to be diagnosed with bipolar

disorder 26

Causality

Inflammatory/Immunologic Response

The theory of bipolar disorder as an illness

of accelerated aging: Implications for clinical

care and research 42

Immunosenescence is associated with

human cytomegalovirus and shortened

telomeres in type I bipolar disorder. 27

Causality

Causality

Treatment

Treatment

Noncompliance

64%

Most frequent cause of recurrence28

Treatment

Lithium

Acute Mania

1800 mg divided BID (ER) TID/QID (IR)

Maintenance

900 -1200 mg per day

Start divided but end the day United

Treatment/Lithium

as effective as divided dosing

spare renal concentrating capacity, thereby diminishing the

risk of diabetes insipitus

reduce the long-term risk of lithium-induced renal

insufficiency

greater adherence

better tolerability29

Treatment/Lithium

Levels

Measure trough levels 4-7 days after

initiating or changing dose

Goal levels

Acute 0.9-1.4 mEq/L

Maintenance 0.8-1.2 mEq/L

Treatment/Lithium

Toxicity

>0.8 mEq/l

Gastrointestinal Symptoms

Nausea, Vomitting, Diarrhea, Stomach

Pains

Neurologic

Dizziness and weakness

Treatment/Lithium

Toxicity

Coarse Tremor

Slurred Speech

Confusion

Hyperreflexia

Psychosis

Treatment

Depakote

Dosing Patient’s weight + 0

Trough plasma concentration between 50

and 125 mcg/mL

Treatment

Depakote

Common Side Effects:

Nausea, Vomitting, Dizziness, Somnelence

and Weight Gain

Thrombocytopenia

Treatment

Depakote

Suicide

Bipolar patients taking Depakote were 2.7

times as likely to commit suicide as those

taking lithium. 30

Treatment

Tegretol (Carbamazepine)

Initiate at 3-5 mg/kg/day divided

Increase up to 10-20 mg/kg/day divided

Trileptal (Oxcarbazepine)

Initiate 300 mg BID

Increase up to 2400 mg (3200)

Treatment

Tegretol

Trough between 6 & 8 mg/L

Should not exceed 10 mg/L 31

Trileptal

Monitoring not indicated

Treatment

Side Effects

Tegretol

Loaded

Trileptal

Fewer & Better Tolerated32

Other Anticonvulsants

Neurontin (Gabapentin) Double-blind studies

failed to demonstrate efficacy.

Gabitril (Tiagabine)

Keppra (Levetiracetam)

Topamax (Topiramate)

Treatment

Lamictal

NOT for Acute Mania

Prevents recurrence of mania/depression

Treatment of Bipolar Depression33

Treatment

Lamictal

“Go low. Go slow. But go!”

-Howard Graitzer, DO

Treatment

Lamictal

Treatment

Lamictal

25 mg/day X 2 weeks, then 50 mg/d X 2

weeks, then 100 mg X 1 week, up to 200 mg

per day. Above 200 mg has not been found

efficacious. 34

Treatment

Avoid Antidepressants

Flip into mania “ 35,37

May not be any more efficacious than

placebo36

Treatment

Second Generation Antipsychotics

Zyprexa (Olanzapine)

Risperdal (Risperidone)

Invega (Paliperidone)

Seroquel (Quetiapine)

Abilify (Aripiprazole)

Saphris (Asenapine)

Latuda (Lurasidone)

Geodon (Ziprasidone) 38

Treatment

SGA

Effective in Acute Mania

Do not induce Depressive Episodes

Have AD Effect 38

Treatment

Second Generation Antipsychotics

Zyprexa (Olanzapine)

Risperdal (Risperidone)

Invega (Paliperidone)

Seroquel (Quetiapine)

Abilify (Aripiprazole)

Saphris (Asenapine)

Latuda (Lurasidone)

Geodon (Ziprasidone) 38

Treatment

Long Acting Depot

Risperdal Consta 25, 37.5, 50 mg q2wks

Invega Sustenna 234, 156, 117 Q 4 wks

Abilify Maintena 400 mg q 4 wks

Treatment

Side Effects

EPS

Metabolic

Sexual Dysfunction

Hyperprolactinemia

Cardiac Arrhythmias

Treatment

Namenda (Memantine) 20-30 mg qd 38,39

Treatment

Mirapex (Pramipexole)

Adjunct treatment

Rapid Cycling

Test Question #2

It is 3 am and you are moonlighting in the

emergency room when a 64 year old woman

is brought in by the county sheriff for

assessment. She is demanding, talking at a

rapid rate, chain smoking, and when she

removes her wrap-around sunglasses, she

looks like this:

Test Question #2

Test Question #2

She is prescribed Lithium, Zyprexa and

Paxil. After admitting her to the psychiatric

ward for stabilization, which medication

option is the best move to stabilizing her

mania?

a. Stop the lithium and prescribe Depakote.

b. Increase the Zyprexa to 50 mg at

bedtime.

c. Taper or discontinue the Paxil.

Test Question #3

You are working in the county jail. One of the prisoners

tested positive for TB exposure several weeks ago.

Prophylactic treatment has been initiated. A correction

officer informs you that this patient is hostile, cursing,

hasn’t slept but two hours per night, and is exposing

himself to female officers. What agent may be the culprit in

causing his behavior?

a. Pruno

b. Methamphetamines

c. isoniazid

d. All of the above

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