jim phelps, m.d. – “got cred?” phelps jr and ghaemi sn. improving the diagnosis of bipolar...

Jim Phelps, M.D. – “got cred?”Jim Phelps, M.D. – “got cred?”

• Phelps JR and Ghaemi SN. Improving the Diagnosis of Bipolar Disorder: Predictive Value of Screening Tests. Journal of Affective Disorders, March 2006.

• Phelps JR, Angst J, Katzow J, Sadler J. Validity and Utility of the Bipolar Spectrum Model. Bipolar Disorders, submitted.

• Phelps J. Bipolar Disorder: Particle or Wave? DSM Categories or Spectrum Dimensions? Psychiatric Times, July 2006.

• Phelps J. Why Am I Still Depressed?: Recognizing and Managing the Ups and Downs of Bipolar II and Soft Bipolar Disorders. McGraw Hill, 2006.

None of my slides, abstracts or handouts contain any advertising, trade names, or product group messages. Any treatment recommendations I make will be based on best clinical evidence or guidelines.

However:Speakers Bureau: Abbott, GSK, Astra ZenecaMcGraw-Hill book royalties

Website Psycheducation.org(free, no advertising, gathers no information)

Cain et al, 2005

The Dirt on Coming Clean: Perverse Effects of Disclosing Conflicts of Interest

Guesser $: Accuracy Advisor $: Accurate or High

Step 1: Diagnosis

Step 2: Treatment

Step 1: Diagnosis

Step 2: Generate “Buy-in” - Rx alliance

- “concordance”- patient/family education

Step 3: Treatment

Step 1: Diagnosis



Step 3: Treatment

1

2

unipolar subthreshold BP II BP I hypomania (BP NOS)

““blue” “green” “yellow” “orange ” blue” “green” “yellow” “orange ” “red” “red”


Bipolarity

Mood Spectrum

AA

BB

CC****


Bipolarity

Mood Spectrum

AA

BB

CC****

(AD risk?)

Step 1: Diagnosis



Step 3: TreatmentWho? How?

When? $$$?

David Miklowitz, Ph.D.

the Bipolar Disorder Survival Guide:What you and your family need to know

Patient/Family Education:Bipolar I

A) PsychEducation.org

Patient/Family Education:Bipolar II

A) PsychEducation.org

Patient/Family Education:Bipolar II

B)

What do I teach and how do I use these resources to do it?

Two Major Paradigm Shifts

1. Unipolar or Bipolar? (DSM) - “Bipolar Spectrum” - BP w/o hypomania/mania?

2. Antidepressants = light infantryMood stabilizers = howitzers

“We may need to reverse that order of preference, or at least put them on an equal plane.”

Frederick Goodwin, Primary Psychiatry, 2005


Ghaemi SN, Saggese J, Goodwin F. Diagnosis of Bipolar Depression. In El-Mallakh R and Ghaemi SN, Bipolar Depression, 2006

El-Mallakh R. Antidepressants in Bipolar Depression. In El-Mallakh R and Ghaemi SN, Bipolar Depression, 2006

Thase M. Treatment-resistant depression and the bipolar spectrum. Primary Psychiatry, 2006; 13 (11), 59-67.

1. Fam Hx Bipolar2. Hyperthymic Personality

3. Onset < age 254. Repeated Episodes

5. Depressions “Atypical”6. Brief Episodes7. Psychosis8. Post-partum Depression

9. 3 or More Antidepressants10. Loss of Response11. Hypomania on AD’s

Bipolar“Soft

Signs”

∙ Ghaemi NS, Ko J, Goodwin F. Cade’s Disease and Beyond: Bipolar Spectrum Disorder. Can J Psychiatry, 2002

Mass. Gen. Hosp. Mass. Gen. Hosp. Bipolarity IndexBipolarity Index “Do you have Bipolar Disorder? “Do you have Bipolar Disorder?

““How bipolar are you?How bipolar are you?””

1. Hypomania/Mania 20 points

2. Family History 20 points

3. Age of (Mood) Onset 20 points

4. Course of Illness 20 points

5. Response to Rx 20 points

Sachs G. Acta Scand Psychiatrica, 2004

Teaching Treatment Principles

1. Target Depression without AntidepressantsAntidepressants can worsen course

9 Non-Antidepressant Antidepressants

2. Psychotherapy5 Bipolar-Specific RCT-based therapies

3. Mood StabilizersWhich?

Five Bipolar-specific RCT-tested therapiesTherapy Reporting Authors Usual # sessions BP I / BP II

Prodrome Detection Perry and colleagues 9 not specified

PsychoeducationColom, Vieta, and

colleagues21 BPI and BP II

Cognitive Therapy(Basco, Rush) Lam

and colleagues14 BP I

Interpersonal/ Social Rhythm

Frank and colleagues -- not specified

Family-Focused Therapy

Miklowitz and colleagues

21 BPI and BP II

RCT results, example

Psychoeducation

Harvard Bipolar Clinic

• Treatment contract

http://www.manicdepressive.org/images/contract.pdf

• Resource Center

http://www.manicdepressive.org/tools_clinical.html

Step 1: Diagnosis



Step 3: Treatment

Phelps EA et al. Nat Neurosci. 2005

Rx AllianceTrust Beats Rationality

- Economic Psychology



- Economic Psychology- $1 or $1.50 or $0



- Economic Psychology- $1 or $1.50 or $0- Neutral, “good”, “bad” Hx



- Economic Psychology- $1 or $1.50 or $0- Neutral, “good”, “bad” Hx- Persist giving if good hx- Even when understanding all three behave the same



A “Spectrum” View of Bipolarity

UP BP

BP II BP IBP NOScyclothymia

Antidepressants

Mood stabilizers Antidepressants

Mood stabilizers

SwitchingSwitching

Mixed (Mixed (↑↑ Suicidal) Suicidal)

↑ ↑ CyclingCycling

Kindling? Kindling?

Li+ ToxicityLi+ Toxicity

Weight GainWeight Gain

Rash, InteractionsRash, Interactions

TD, Diabetes, CVDTD, Diabetes, CVD

??

????

??

International Society for Bipolar DisorderInternational Society for Bipolar Disorder Committee on Diagnosis

Chair: Nassir Ghaemi

Pure Mania: Paul Grof, Laksmi Yatham, Frederick CassidyMixed States: Roger McIntyre, Mario Maj, Franco BenazziDepression: Philip Mitchell, Prof. Johnson, Guy Goodwin, Robert

HirschfeldRapid Cycling: Michael Bauer, David Dunner, Benny Lafer, Serge

BeaulieuType II: Eduard Vieta, Trisha Suppes, William FulfordChild: Eric Youngstrom, Robert Findling, Boris Birmaher, Kenneth

SchaffnerSpectrum: James Phelps, Jacob Katzow, Jules Angst, John Sadler,

Fred Goodwin

A “Spectrum” View of Bipolarity

UP BP

BP II BP IBP NOScyclothymia

Bipolar Spectrum Disorder

AD-inducedAD-induced

BP NOS-RBP NOS-R

“Then A Miracle

Occurs…”


1. Unipolar or Bipolar? (DSM) - “Bipolar Spectrum” - BP w/o hypomania/mania?

2. Antidepressants = light infantryMood stabilizers = howitzers

“reverse that order of preference, or at least put them on an equal plane.”

Frederick Goodwin, M.D.Frederick Goodwin, M.D.

- Manic-Depressive Illness, 1990- former head of NIMH

“[Doctors] think of antidepressants as light, easy, uncomplicated drugs; and mood stabilizers as heavy drugs that should be reserved as a last resort. But in fact, recent data suggest that we may have to reverse that order of preference, or at least put them on an equal plane.”

Primary Psychiatry, 2005Three RCT’s, 1 case series

…. et al Yr N Rx Findings

Prien ’73 44 Li v. IMI v. PBO Hosp’ or Δ rx, 24 mos: Li > IMI ; IMI = PBO

Wehr ’79 5 Li v. Li + DMI Nurse ratings, 19 mos: Li + DMI > Li; cycle rate increase

Quitkin ’81 75 Li v. Li + IMI RDC episodes, 19 mos avg: Li = combination

Mania: 10% Li only, 24% Li + IMI (significant only in )Kane ’82 27 Li v IMI, v.

Li/IMI, v. PBO11 mos: Li > IMI = PBO

Prien ’84 117 Li v. Li + IMI RDC episodes, 24 mos: Li = combination

Sachs ’94 15 Li + BUP or DMI DSM episodes, up to 15 mos: equal efficacy

Amsterdam ’98 80 FLX v. PBO, in BP II and UP

DSM episodes, up to 14 mos: FLX efficacy similar in BP II and UP; higher switch rate in BP II

Ghaemi ‘05 69 AD + MS v. MS Open, no blind, ongoing.***

Leverich ‘06 159 BUP, SRT, VEN with MS

Blind, no placebo; ~25% remission at 1 year

1. Long-term Antidepressants in BP depression

Leverich et al, Am J Psych Feb 2006; Post et al, Brit J Psych, Aug 2006

N=150 BP I and BPII 15-30% in 10 weeks15-30% in 10 weeks

(4-15% by YMRS (4-15% by YMRS >>13)13)

2. Antidepressant-Induced 2. Antidepressant-Induced SwitchingSwitching

3. Antidepressant-Induced Shortening of Bipolar Cycle Length

0

50

100

150

200

250

300

Off On Off On Off

Cyc

le le

ng

th (

day

s)

Wehr TA, Goodwin FK. Arch Gen Psychiatry. 1979

(3b) NIMH RCT: AD replaced with PBO

Wehr et al. Am J Psych, 1988

Replicated earlier study, extended it: 20% of rx-resistant sample have cycling induced by AD’s.

Antidepressant-associated chronic irritable dysphoria (acid)

in bipolar disorder: a case series.

El-Mallakh and Karippot, J Affect Disord. 2005 Feb

RESULTS: A triad of dysphoric mood, irritability, and middle insomnia that is frequently associated with occupational and social dysfunction can occur in some bipolar patients receiving antidepressants for at least 3 years.

Principles For Long-term Mgm’t

1. Target Depression without AntidepressantsAntidepressants can worsen course




Can-SAD: Lights vs. fluoxetine

Lam et al. Am J Psych May 2006

A Fifth Photoreceptor A Fifth Photoreceptor

Glickman, Brainard et al. J Neurosci., 2001


Glickman, Brainard et al. J Neurosci., 2001

“…446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion…. a novel opsin photopigment in the human eye that mediates circadian photoreception…

Evidence for a novel circadian photoreceptor.

Glickman, Brainard et al. J Biol Rhythms. 2003

Inferior retinal light exposure is more effective than superior retinal

exposure in suppressing melatonin in humans.


Glickman, Brainard et al. Biol Psychiatry. 2006 Mar

Light therapy for seasonal affective disorder with blue narrow-band light-emitting diodes (LEDs).

“Narrow bandwidth blue light … outperforms dimmer red light in reversing symptoms of major depression with a seasonal pattern.”


Glickman, Brainard et al. Biol Psychiatry. 2006 Mar

Terman: Dawn

Sim’ vs. Light

Am J Psych Dec 2006

Terman: Dawn

Sim’ vs. Light

Am J Psych Dec 2006

0

2

4

6

8

10

12

14

16

1 2 3

HA

M-D Light Box

Dawn Simulator


1. Target Cycling, Not Mood Du JourAntidepressants can worsen course?




Blue-Blocking LensesBlue-Blocking Lenses

Preserve Melatonin

Kayumov et al. J Clin Endocrinol Metabolism, 2005


1. Target Cycling, Not Mood Du JourAntidepressants can worsen course?




Indications Approved by FDA

ManiaMixed

EpisodesMaintenance/ Prophylaxis Bipolar II

Bipolar Depression

Monotherapy

Lithium (Eskalith, Lithobid) 1970 1974

Valproate (Depakote) 1995

Divalproex ER (Depakote ER) 2005 2005

Olanzapine (Zyprexa) 2000, 20031 2004 2003

Risperidone (Risperidal) 2003, 20031 2003

Quetiapine (Seroquel) 20041,2 2006 2006

Ziprasidone (Geodon) 2004 2004

Aripiprazole (Abilify) 2004 2004 2005

Lamotrigine (Lamictal) 2004

Carbamazepine ER (Equetro) 2004 2004

Combination Therapy

Olanzapine/fluoxetine (Symbyax) 2003

Advantages Disadvantages

lithium

valproate

carbamaz’ oxcarbaz’

lamotrigine

olanzapine

quetiapine risp, zip, arip

(Ω-3 fatty acids?)

Mood Stabilizers Advantages Disadvantages

lithium

valproate

carbamaz’ oxcarbaz’

lamotrigine

olanzapine (Ω-3 fatty acids?)

How to choose? – it’s like hamburgers…

Adherence: Why Not Take Lithium?

B

B

D

D

W

W

C

C

H

M

HM

Pope M, Scott J. J Affect Dis, 2003

(Previously Not Adherent)


B

B

D

D

W

W

C

C

H

M

HM



B

B

D

D

W

W

C

C

H

M

HM


B DW


B

B

D

D

W

W

C

C

H

M

HM


C

McElroy et al

Mackinnon & Pies. Bipolar Disorder, 2006

Bipolar “Mixity”Bipolar “Mixity”

Bipolar “Mixity”


CREB

PI-3-k MAP/ERK

Akt

Bad

Bcl-2

BDNF

GSK-3β

Glucose Transporter

Cortisol

GRBAG-1

Glutamate

NMDA

TrkB

PKANE

Serotonin

PTP

ROS

lithium

Ca++

valproate

Brodmann Area 25

Serotonin Transporter DNA

Area 25/Amygdala Circuit

jim phelps, m.d. – “got cred?” phelps jr and ghaemi sn. improving the diagnosis of bipolar...

Documents

downs of bipolar

treatment slide

bipolar spectrum disorder

diagnosis of bipolar

b slide

bipolar spectrum model

high slide

information slide