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Bipolar DisordersBipolar Disorders

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U-M Depression Center and Ann Arbor U-M Depression Center and Ann Arbor Public LibraryPublic Library Presentation on topics of interest relevant to Presentation on topics of interest relevant to

mental health in communitymental health in community Panel of experts from U-M Depression Center Panel of experts from U-M Depression Center

and Professionals in communityand Professionals in community Q/A formatQ/A format

Improve community awareness of resources Improve community awareness of resources available.available.

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Bipolar Disorder: March 29th Bipolar Disorder: March 29th

Suicide: May 24thSuicide: May 24th

Sleep and Depression: October 2006Sleep and Depression: October 2006

Aretaeus of CappadociaAretaeus of Cappadocia Melancholia & maniaMelancholia & mania

2 forms of the same 2 forms of the same diseasedisease

Mania manifests as Mania manifests as euphoria, but others euphoria, but others display furious ragesdisplay furious rages

Melancholics – possible Melancholics – possible for them to fly into rage..for them to fly into rage..

First to describe mixed affect

Understanding Affective Understanding Affective DisordersDisorders

Kraepelin proposed Kraepelin proposed affect to consist of 3 affect to consist of 3 componentscomponents VolitionVolition

Energy & DriveEnergy & Drive

EmotionEmotion Happy / SadHappy / Sad

IntellectIntellect Rate of thoughtsRate of thoughts Content of thoughtsContent of thoughts

Celebrities with Bipolar DisorderCelebrities with Bipolar Disorder

Kay Jamison, PhD

Margot Kidder

Ted Turner

Axl RoseJean-Claude Van Damme

Ben Stiller

Sylvia Plath

Affect - Affection

Volition – the drive to care for our offspring

Emotion – the love for our children

Intellect – the thoughts & speech related to our interactions with family and loved ones

Normal Affect

Volition

Emotion

Intellect

- Moods and disposition fluctuate over time

VolitionEmotion

Intellect

Depression

5

0

10

Mania

Volition

Emotion

Intellect

Volition

Emotion

Intellect

Mixed Affect

Wilhelm GreisingerWilhelm Greisinger MittelformenMittelformen

In which a change from In which a change from depression to manic exaltation depression to manic exaltation occurs.occurs.

““Melancholia with destructive Melancholia with destructive drives”drives”

““Melancholia with long lasting Melancholia with long lasting exaltation of volition”exaltation of volition”

In their mild forms, mittleformen In their mild forms, mittleformen are indistinguishable from are indistinguishable from personality deviations.personality deviations.

1817 - 1868

Epidemiology of Bipolar DisorderEpidemiology of Bipolar Disorder

ECA study lifetime prevalence ECA study lifetime prevalence 1.3%1.3% Bipolar I Bipolar I 0.8% 0.8% Bipolar II Bipolar II 0.5% 0.5%

Including “bipolar spectrum” disorders Including “bipolar spectrum” disorders BP Not otherwise specified BP Not otherwise specified ~3%~3%

No male or female predominance No male or female predominance Females with more depressionFemales with more depression

ECA study = Epidemiological Catchment Area survey. Bebbington P, Ramana R. Soc Psychiatry Psychiatr Epidemiol. 1995;30:279-292. Dunner DL. Bipolar Disord. 2003;5:456-463; Lish JD et al. J Affect Disord. 1994;31:281-29.

BP Disorder & GeneticsBP Disorder & Genetics

BP disorder is 80% geneticsBP disorder is 80% genetics - And 100% environmental!- And 100% environmental!

Having a BP sibling or parent increases Having a BP sibling or parent increases likelihood of developing BP likelihood of developing BP fivefoldfivefold compared compared to general population.to general population. Risk increases with increasing number of affected in Risk increases with increasing number of affected in

family.family. Overlap with genetic risk for other mood, Overlap with genetic risk for other mood,

anxiety, and psychotic disorders.anxiety, and psychotic disorders.

Spectrum of Bipolar Spectrum of Bipolar DisordersDisorders

Bipolar IBipolar I Bipolar IIBipolar II Major depression with a strong family history of Major depression with a strong family history of

bipolar disorderbipolar disorder HypomaniaHypomania Antidepressant-induced mania and hypomaniaAntidepressant-induced mania and hypomania CyclothymiaCyclothymia Rapidly changing mood swingsRapidly changing mood swings NOSNOS Secondary mania, due to other illnesses or drugsSecondary mania, due to other illnesses or drugs

Adapted from American Psychiatric Association. Practice Guideline for the Treatment of Patients with Bipolar Disorder. 2nd ed. Washington, DC; 2002.

Bipolar DisordersBipolar Disorders

Stahl SM. Essential Psychopharmacology. New York, NY: Cambridge University Press; 2000.

SUBSYNDROMAL DEPRESSION

NORMALMOOD

HYPOMANIA*

MIXED EPISODE†

MANIA

*Hypomania is a milder form of mania with similar yet less severe symptoms and less overall impairment.

†Mixed Episode is an episode that simultaneously presents symptoms of both depression and mania.

DEPRESSION

Misdiagnosis of Bipolar DisorderMisdiagnosis of Bipolar Disorder

Often mistaken for depression (40%Often mistaken for depression (40%––70% 70% initially misdiagnosed)initially misdiagnosed)1-31-3

Often see several clinicians without Often see several clinicians without accurate diagnosisaccurate diagnosis22

Mean time to diagnosis long (8 yearsMean time to diagnosis long (8 yearsin 1 study)in 1 study)3,43,4

Rate of misdiagnosis worse with Rate of misdiagnosis worse with comorbiditycomorbidity22

1. Bowden CL. J Affect Disord. 2005:84:117-125; 2. Thomas P. J Affect Disord. 2004;79(Suppl 1):S3-S8; 3. Baldessarini R et al. Am J Psychiatry. 1999;156:811-812; 4. Tondo L et al. Am J Psychiatry. 1998;155:638-645.

Misdiagnosis of Bipolar DisorderMisdiagnosis of Bipolar Disorder 2000 NDMDA initial diagnosis (69%)2000 NDMDA initial diagnosis (69%)

NDMDA = National Depressive and Manic-Depressive Association; N = 400NDMDA = National Depressive and Manic-Depressive Association; N = 400

Hirschfeld RM, et al. Hirschfeld RM, et al. J Clin PsychiatryJ Clin Psychiatry. 2004;65(suppl 15):5-9.. 2004;65(suppl 15):5-9.

60

26

18 1714

0

10

20

30

40

50

60

Depression

Anxiety

Schizophrenia

Cluster B

Alcohol abuse

Per

cen

t

Onset of Bipolar DisorderOnset of Bipolar Disorder

Onset in teens for most patientsOnset in teens for most patients(peak ages, 15(peak ages, 15––19 years) 19 years)

Late onset less rare than was thought Late onset less rare than was thought (possibly 6% aged >60 years)(possibly 6% aged >60 years)

Relapse frequent (75%Relapse frequent (75%––90%)90%)

Bebbington P, Ramana R. Soc Psychiatry Psychiatr Epidemiol. 1995;30:279-292; Sajatovic M et al. Am J Geriatr Psychiatry. 2005;13:282-289; Gitlin MJ et al. Am J Psychiatry. 1995;152:1635-1640.

McLean Harvard First-Episode McLean Harvard First-Episode Mania studyMania study

239 BP with first Manic/mixed episode239 BP with first Manic/mixed episode 173 recruited for study173 recruited for study

151 followed for an average of 4.86 years151 followed for an average of 4.86 years

Recovery at 2 yearsRecovery at 2 years Syndromal (DSMIV)98%Syndromal (DSMIV)98% Symptomatic (YM) 72%Symptomatic (YM) 72% Functional (occupational) 43%Functional (occupational) 43%

Disability With Bipolar DisorderDisability With Bipolar Disorder

Bipolar disorder is the 6th leading cause of Bipolar disorder is the 6th leading cause of medical disability worldwide among people medical disability worldwide among people aged 15 to 44 years aged 15 to 44 years

Bipolar disorder is associated with a Bipolar disorder is associated with a greater degree of disability than greater degree of disability than osteoarthritis, human immunodeficiency osteoarthritis, human immunodeficiency virus infection, diabetes, and asthmavirus infection, diabetes, and asthma

Murray CJ, Lopez AD. Lancet. 1997;349:1436-1442.

Social Impact of Bipolar DisorderSocial Impact of Bipolar Disorder

Unemployment rate 60%, includes Unemployment rate 60%, includes college graduatescollege graduates

65% report impaired long-term 65% report impaired long-term relationshipsrelationships

Hirschfeld MA et al. J Clin Psychiatry. 2003;64:161-17; Kupfer DJ et al. J Clin Psychiatry. 2002;63:120-125.

Economic Impact of Bipolar DisorderEconomic Impact of Bipolar Disorder

The estimated annual societal cost of The estimated annual societal cost of bipolar disorder ranges from $10 billion to bipolar disorder ranges from $10 billion to $45 billion$45 billion

Indirect costsIndirect costs 49.5 lost workdays/year/patient49.5 lost workdays/year/patient 180 million lost workdays/year 180 million lost workdays/year $25.9 billion salary-equivalent lost/year$25.9 billion salary-equivalent lost/year

Wyatt RJ, Henter I. Soc Psychiatry Psychiatr Epidemiol. 1995;30:213-219; Greenberg PE et al. J Clin Psychiatry. 1993;54:405-418. Begley CE et al. Pharmacoeconomics. 2001;19:483-495.

Epidemiological Catchment Area Survey Epidemiological Catchment Area Survey (ECA): Comorbidity and Bipolar Disorder(ECA): Comorbidity and Bipolar Disorder

Regier DA et al. JAMA. 1990;264:2511-2518; Chen YW, Dilsaver SC. Am J Psychiatry. 1995;152:280-282; Chen YW, Dilsaver SC. Psychiatry Res. 1995;59:57-64.

% P

atie

nts

Alcohol-use

Disorder

Substance-use

Disorder

PanicDisorder

OCD

13.5

46.2

6.1

40.7

0.8

20.8

2.6

21

0

10

20

30

40

50

General Population

Bipolar Disorder

Substance-Use Disorder & BPDSubstance-Use Disorder & BPD

Bipolar disorder with co-existing substance-use Bipolar disorder with co-existing substance-use disorder is associated with an increase in disorder is associated with an increase in Suicide attemptsSuicide attempts Suicidal ideasSuicidal ideas Seeking hospital admissionSeeking hospital admission Hospital admissionHospital admission ViolenceViolence Aggressive behaviorAggressive behavior Doubled risk of suicideDoubled risk of suicide

Potash JB et al. Am J Psychiatry. 2000;157:2048-2050; Scott H et al. Br J Psychiatry. 1998;172:345-350; Comtois KA et al. Biol Psychiatry. 2004;56:757-763; Strakowski SM, DelBello MP. Clin Psychol Rev. 2000;20:191-206; Strakowski SM et al. Arch Gen Psychiatry. 2005;62:851-858.

Substance-Use in BPD: Treatment IssuesSubstance-Use in BPD: Treatment Issues

Less likely to respond to treatmentLess likely to respond to treatment11

Less likely to adhere to medicationsLess likely to adhere to medications1,21,2

Less likely to adhere to lithium treatmentLess likely to adhere to lithium treatment

Less likely to gain full remission and Less likely to gain full remission and resolve symptoms resolve symptoms

Remission during hospitalization less likely Remission during hospitalization less likely to occur vs no substance-use disorder to occur vs no substance-use disorder

1. Goldberg JF et al. J Clin Psychiatry. 1999;60:733-740; 2. Aagaard J, Vestergaard P. J Affect Disord. 1989;12:259–266; 3. Strakowski SM et al. Arch Gen Psychiatry. 1998;55:49-55.

APA Treatment Guidelines for Comorbid APA Treatment Guidelines for Comorbid BPD and Substance-Use DisorderBPD and Substance-Use Disorder

Treatment should proceed concurrently, Treatment should proceed concurrently, preferably in a dual-diagnosis programpreferably in a dual-diagnosis program

Alcohol abuse may affect bipolar Alcohol abuse may affect bipolar pharmacotherapypharmacotherapy Alcohol-related dehydration may raise serum Alcohol-related dehydration may raise serum

lithium to toxic levelslithium to toxic levels Hepatic dysfunction may alter plasma levels Hepatic dysfunction may alter plasma levels

of valproate and carbamazepineof valproate and carbamazepine

American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Available at: http://www.psych.org/psych_pract/treatg/pg/Practice%20Guidelines8904/BipolarDisorder_2e.pdf. Accessed January 24, 2006.

Medical Conditions & BP Medical Conditions & BP

MigraineMigraine Thyroid diseaseThyroid disease

LithiumLithium Type 2 diabetesType 2 diabetes

AntipsychoticsAntipsychotics Obesity Obesity

Mood stabilizersMood stabilizers AntipsychoticsAntipsychotics

Polycystic Ovarian SyndromePolycystic Ovarian Syndrome Valproate and other anticonvulsantsValproate and other anticonvulsants

Multiple sclerosisMultiple sclerosis Multiple episodes may increase risk of dementiaMultiple episodes may increase risk of dementia

Causes of Medical Problems Causes of Medical Problems in Bipolar Disorder in Bipolar Disorder

Poor dietPoor diet SmokingSmoking11

Obesity (32%)Obesity (32%)22

MedicationsMedications InactivityInactivity

Underutilization of medical resourcesUnderutilization of medical resources Nonadherence (>50%)Nonadherence (>50%)33

1. Breslau N et al. Psychological Medicine. 2004;34:323-333; 2. Fagiolini A et al. J Clin Psychiatry. 2002;63:528-533;3. Fleck DE. J Clin Psychiatry. 2005;66:646-652; 4. Dailey LF et al. J Clin Psychiatr. 2005;66:477-484.

Obesity in Bipolar DisorderObesity in Bipolar Disorder

35.4% of patients with bipolar disorder had BMI 35.4% of patients with bipolar disorder had BMI ≥≥30 mg/kg30 mg/kg2 2

Decreased sense of well being and QOLDecreased sense of well being and QOL22

Increased relapses of depressive episodesIncreased relapses of depressive episodes2,32,3 More likely to have made a suicide attemptMore likely to have made a suicide attempt44

Bipolar disorder treatments have been Bipolar disorder treatments have been associated with weight gain and endocrine associated with weight gain and endocrine changes; new weight gain increases IR and may changes; new weight gain increases IR and may promote PCOS in predisposed womenpromote PCOS in predisposed women55

IR = insulin resistance; PCOS = polycystic ovarian syndrome.1. Fagliolini A et al. Am J Psychiatry. 2003;160:112-117; 2. McLaren KD, Marangel LB. Ann Gen Hosp Psychiatry.2004;3:7-17; 3. Post RM. J Clin Psychiatry. 2005;66(Suppl 5):5-10; 4. Osby U et al. Arch Gen Psychiatry. 2001;58:884-850; 5. Rasgon NL et al. Bipolar Disord. 2005;7:246-259.

Treatment Decisions: Bipolar Treatment Decisions: Bipolar DisorderDisorder

Selection of Initial Intervention

Sequential Care Most Benign

Urgent Care Most Effective

MonotherapyStart LowGo Slow

Combination TherapyAggressive Titration

toEffective Dose Range

Sachs GS. Managing Bipolar Affective Disorder. Science Press Ltd: London, UK; 2004.

Guidelines for Acute ManiaGuidelines for Acute Mania

Fountoulakis KN, et al. J Affect Disord. 2005;86:1-10.

Keck PE Jr, et al. Postgrad Med Special Report. 2004:1-120.

American American Psychiatric Psychiatric

Association, Association, 19941994


Association, 2002Association, 2002

Expert Expert Consensus Consensus Guidelines, Guidelines,

20042004

11stst ChoiceChoice

LiLi SevereSevere: Li or Vp+AP: Li or Vp+APMild-ModMild-Mod: Li, Vp, Olz: Li, Vp, Olz

Li, Vp, OlzLi, Vp, Olz

22ndnd ChoiceChoice

Vp, CbzVp, CbzAPs only for the APs only for the rapid control of rapid control of agitationagitation

Various Various combinations of two combinations of two 11stst choice agents choice agents ECTECT

Cbz, Risp, Cbz, Risp, QuetQuet

AP = antipsychotic; Cbz = carbamazapine; ECT = electroconvulsive therapy; Li = lithium; Olz = olanzapine; Quet = quetiapine; Risp = risperidone; Vp = valproate.

Guidelines for Acute Bipolar Guidelines for Acute Bipolar DepressionDepression








20042004

11stst ChoiceChoice

LiLi Li or La or Li+ADLi or La or Li+ADECTECT

Li, LaLi, La

22ndnd ChoiceChoice

Vp, CbzVp, CbzECTECTAD are AD are considered to considered to worsen the long-worsen the long-term course of term course of the illnessthe illness

Combination of 1Combination of 1stst choice agentschoice agentsECTECT

Li or La, or Li or La, or Li+AD,Li+AD,Quet, RispQuet, Risp

AD = antidepressant; Cbz = carbamazapine; ECT = electroconvulsive therapy; La = lamotrigine; Li = lithium; Olz = olanzapine; Quet = quetiapine; Risp = risperidone; Vp = valproate.

Guidelines for Bipolar Guidelines for Bipolar MaintenanceMaintenance








20042004

11stst ChoiceChoice

Continue the Continue the treatment proved treatment proved efficient during efficient during the acute phasethe acute phase

Li or Vp possibly Li or Vp possibly Cbz, La, OCbzCbz, La, OCbzContinue the Continue the treatmenttreatment

Li, Vp, OlzLi, Vp, Olz

22ndnd ChoiceChoice

ECTECT

Combination of Combination of 11stst choice agents choice agents

ECTECT

Combination of 1Combination of 1stst choice agentschoice agentsAP should be AP should be discontinueddiscontinued

Cbz, Risp, Cbz, Risp, Quet, Arip, Quet, Arip, ZiprZipr

Arip = aripiprazole; Cbz = carbamazapine; ECT = electroconvulsive therapy; La = lamotrigine; Li = lithium; OCBz = oxcarbamazepine; Olz = olanzapine; Quet = quetiapine; Risp = risperidone; Vp = valproate; Zipr = ziprasidone.

Suicide Risk in Bipolar DisorderSuicide Risk in Bipolar Disorder

Patients with bipolar disorder have a higher Patients with bipolar disorder have a higher risk of suicide than patients with any other risk of suicide than patients with any other psychiatric or medical illnesspsychiatric or medical illness

Odds ratio for suicide attempts is 6.2, higher Odds ratio for suicide attempts is 6.2, higher than any other disorder, including depressionthan any other disorder, including depression

Woods SW. J Clin Psychiatry. 2000;61(Suppl 13):38-41; Chen YW, Dilsaver SC. Biol Psychiatry. 1996;39:896-899;Goldberg JF, Harrow M. J Affect Disord. 2004;81:123-131.

Sta

nd

ard

ized

Mo

rtal

ity

Rat

io*

Increased Mortality in Patients Increased Mortality in Patients With Bipolar DisorderWith Bipolar Disorder

*SMR = standardized mortality ratio: observed events ÷ expected events; †Unnatural = accidents, suicide, homicide, undetermined deaths.GI = gastrointestinal.Osby U et al. Arch Gen Psychiatry. 2001;58:884-850.

All Causes

CVD GI Unnatural†Cerebro-vascular

Cancer

2.5 2.71.9

2.6

1.1 1.21.9 2 2 1.9

8.6

12.7

0

2

4

6

8

10

12

14

Males (n=6578)Females (n=8808)

Suicide prevention and Suicide prevention and LithiumLithium

In a meta-analysis of 22studies – the computed risk-ratio for on vs off lithiumwas 8.85

Tondo et al, 2001 Acta Psych Scand

BP Concluding statements..BP Concluding statements..

Bipolar Disorders are a category of mood Bipolar Disorders are a category of mood disorders - with a broad range of severity.disorders - with a broad range of severity.

BP is eminently treatable.BP is eminently treatable. But requires treatment to be ongoing But requires treatment to be ongoing

Collaboration between Treatment team and patientCollaboration between Treatment team and patient BP is a serious illness.BP is a serious illness.

Lives, families, and careers affectedLives, families, and careers affected People die from itPeople die from it

Prechter Bipolar Genes ProjectPrechter Bipolar Genes Project

GoalsGoals Determine what keeps BP patients well, and Determine what keeps BP patients well, and

what causes problemswhat causes problems Find the genes involvedFind the genes involved

StudyStudy Track participants for 5 years through Track participants for 5 years through

interview, questionnaires, cognitive testinginterview, questionnaires, cognitive testing Collect blood sample for DNA analysisCollect blood sample for DNA analysis

Prechter Bipolar Genes ProjectPrechter Bipolar Genes Project

For more information:For more information: www.hcpfmd.orgwww.hcpfmd.org www.depressioncenter.orgwww.depressioncenter.org

New toll-free #:New toll-free #: 1-877-UM GENES1-877-UM GENES (1-877-864 3637)(1-877-864 3637) Email: Email:

[email protected]@umich.edu

Panel MembersPanel Members Melvin McInnis, MDMelvin McInnis, MD

University of MichiganUniversity of Michigan Cheryl King, PhDCheryl King, PhD

University of MichiganUniversity of Michigan Juan Lopez, MDJuan Lopez, MD

University of MichiganUniversity of Michigan Shabnum H. Sheikh, MDShabnum H. Sheikh, MD

St Joseph Mercy HospitalSt Joseph Mercy Hospital Jon-Kar Zubieta, MDJon-Kar Zubieta, MD

University of MichiganUniversity of Michigan Katharene Schoof, MSW, ACSW Katharene Schoof, MSW, ACSW

University of MichiganUniversity of Michigan

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