BIPOLAR DISORDERS “AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH”

BIPOLAR DISORDERS “AFTER ALL, THERE IS NOTHING AS INTERESTING AS PEOPLE, AND ONE CAN NEVER STUDY THEM ENOUGH” VINCENT VAN GOGH Brought to you by BIPOLAR DISORDERS Closely Kept Secrets New Treatments B.

“AFTER ALL, THERE IS NOTHING AS INTERESTING AS

PEOPLE, AND ONE CAN

NEVER STUDY THEM ENOUGH”

VINCENT VAN GOGH

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BIPOLAR DISORDERS

• Closely Kept Secrets

• New Treatments

EPIDEMIOLOGY OF BIPOLAR DISORDER

• Prevalence is underestimated at 1%

• Prevalence is probably 2%

• Calgary est 2%x890000=17,800 citizens

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COMORBID DISORDERS

• Substance Abuse – At least 61%

• Alcohol, Cocaine, THC

• Effect – More mixed and rapid cycling, poorer

response to Lithium, slower time to recovery, and more lifetime hospitalizations

• Narcissistic PD

• Borderline PD

• 20-30% OCD, Panic Disorder

DIFFERENTIAL DIAGNOSIS

• Schizophrenia, Schizoaffective disorder

• Substance Abuse – Stimulants

• Pseudo-Unipolar Disorder

• Steroids, Ginseng, Valerian root

• Syphilis, Hyperparathyroidism

• Borderline, Narcissistic and Histrionic

Personality disorder Brought to you by

• Much more likely to be delusional and co

morbid for substance abuse

• More likely to be irritable and misdiagnosed

as conduct disorder

• 60% of first episodes precipitated by

psychosocial, physical, or drug causes 30% of second episodes

• None of fourth episodes

• Illness starts as exogenous and becomes

more endogenous

• Concept of kindling

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SCREENING QUESTIONS

• Have you ever had a period of a week or so

when you felt so happy and energetic that

your friends told you that you were talking

too fast or that you were behaving

differently and strangely?

• Has there been a period when you were so

hyper and irritable that you got into

arguments with people?

SCREENING QUESTIONS

• Has anyone ever called you manic before?

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• Distractibility

• Indiscretion (pleasurable activities)

• Grandiosity

• Flight of ideas

• Activity increase

• Sleep deficit (decreased need)

• Talkativeness (pressured speech)

• Were you having trouble thinking or

concentrating?

• Was this because things around you or even

your thoughts were getting you off track?

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• During the period we were talking about, how

were you spending your time?

• Were you doing things that caused trouble for you

or your family?

• Were you doing things that showed a lack of

judgment, such as driving too fast, running red

lights, or spending too much?

• Were you doing sexual things during this

this period that was unusual for you?

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• During this period did you feel so confidant

that you felt you could conquer the world?

• What was your best idea when you felt that

FLIGHT OF IDEAS

• During this period did you have so many

thoughts, or were they so fast, that you

could barely keep up to them?

• Did it feel like your thoughts were racing?

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ACTIVITY INCREASE

• During that period, were you more active

than usual?

• Were you constantly starting new projects

and hobbies, working into the night?

SLEEP DEFICIT

• During that period, did you need less sleep?

• Did you ever stay up all night doing all

kinds of things, like working on projects or phoning people?

• Did your sleep duration become reduced

and still you had lots of energy?

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• During this period, were you talking more

than usual for you?

• Were you talking so much that people had

to interrupt you to speak to you?

• Were you using the phone more than usual

for you?

• Denial and lack of insight rule the day

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TREATMENT OPTIONS

• Hospitalization for mania, severe depression

• Mood stabilizers, antipsychotics and

antidepressants

• ECT – most effective treatment

• Supportive psychotherapy and CBT

• Lifestyle change

• Substance abuse treatment

LITHIUM CARBONATE

• Most effective medication

• SE’s include teratogenicity, tremor, renal dysfunction,

acne, hypothyroidism, gastric upset, cardiac conduction problems, cognitive impairment

q6mo.

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• 500 – 2000 mg/d; Highest blood level for

effect Highest dose is 60 mg/kg/d

• SE’s – GI upset, weight gain, alopecia,

teratogenicity, liver problems

• Best for mixed states, rapid cycling, secondary

mania Ineffective for depression

• Selenium for hair loss

ATYPICAL ANTIPSYCHOTICS

• Olanzepine – 2.5-20 mg/d; very effective;

significant wt gain and lipid problems in

some

• Risperdal - 5-4.0 mg/d; more EPS and

increased prolactin in some

• Clozapine - For truly refractory patient, but

can be remarkably effective Slow response, serious SE profile and significant wt gain

Olanzepine Efficacy for Mania: Two Placebo-Controlled Studies

• Both double-blind, placebo-controlled, inpatient

– Study I: 3 weeks*

– Study II: 4 weeks**

• Olanzapine dosage: 5-20 mg/day

– Starting daily dose: Study I - 10 mg

Study II - 15 mg

– Mean modal daily dose: Study I - 14.9 mg

Study II - 16.4 mg

• DSM-IV Bipolar I Disorder, manic or mixed

• Lorazepam use limited to initial study phase

*Study I -Tohen et al, Am J Psych 1999;

** Study II- Tohen et al, XI World Congress of Psychiatry, Hamburg Germany, 1999

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Olanzepine Grp Superior YMRS

Study I three weeks four weeks Study II

Antimanic Efficacy of Olanzapine Is Significant Starting at the First Assessment

(Week 1 Y-MRS)

-60 -50 -40 -30 -20 -10 0

Placebo Olanzapine

1

*

*

*

*

* p < 05 Response curve illustrates four week study of olanzapine (n=54) vs placebo

(n=56) for acute mania (four week study II)

-20 -15 -10 -5 0

Similar Y-MRS Improvement in Non-Psychotic and Psychotic Subjects

* p=0.88; ** p=0.41 No difference in mania improvement among olanzapine-treated

subjects with and without psychotic features

Mean

Change

(LOCF)

Study I three weeks four weeks Study II

**

*

Non-psychotic Psychotic

There was no difference in antimanic response (Y-MRS Total beginning to endpoint improvement,

four-week study II) between olanzapine-treated patients in manic or mixed episodes (p=.681)

Y-MRS Total: Manic vs Mixed Episodes

-20 -15 -10 -5 0

Mean

Change

Manic episode n=31

Mixed episode n=23

-15.39 -13.96

Study II four weeks

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In Patients Presenting with

-18 -15 -12 -9 -6 -3 0

Mean

Change

There was no difference in antimanic response (Y-MRS Total beginning to endpoint

improvement, four-week study II) between olanzapine-treated patients with history of good

vs poor response to lithium treatment for mania (p=.641)

Responder n=18

Non-responder n=24

Most Recent Lithium Response:

Y-MRS Total: Lithium Responders vs

Study II four weeks

Baker RW et al Bipolar Disorders Conference Phoenix, Arizona, January 2000.

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Y-MRS Total: Valproic Acid

Responders

vs Non-Responders

-20 -15 -10 -5 0

-11.73

-14.67

There was no difference in antimanic response (Y-MRS Total beginning to endpoint

improvement, four-week study II) between olanzapine-treated patients with history of good

vs poor response to valproate treatment for mania (p=.546)

Non-responder n=21

Most Recent Valproic Acid Response:

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Treatment-Emergent Adverse Effects During Acute Mania

SomnolenceDry mouthDizzinessAsthenia

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• Anticonvulsant, least effective new drug

• Most helpful with anxiety, insomnia, pain

• May cause persistent sedation

• Excreted by kidneys only, no drug

interaction

• 1200 to 4000 mg/d.

• Anticonvulsant, best for Bipolar depression

• Improved cognition, excellent tolerance,

serious autoimmune rash

• Valproate interaction

• 12.5 to 25 mg/wk increments Dose range of

75 to 300mg/d

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• May augment other medications?

• Significant cognitive ill effect and paresthesiae

NEVER UNDERESTIMATE LOOKING

GOOD !!!!!!

• 50 mg qhs, increase by 50 mg/wk in divided

doses to maximum of 200 mg bid

THYROID AUGMENTATION

• TSH is not reliable indicator of subclinical

hypothyroidism in mood disorder patients

• T3 and T4 in lower range of “normal” cause

cognitive impairment, relapse and lethargy

• Supplemental T4 caused 10/11 Li refractory to

respond

• Large study showed no bone density effect of

high dose T4 treatment Brought to you by

NEVER GIVE UP

It will help patient to be inspired by

us, rather than the other way around

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