Bipolar a complex disorder

Bipolar Disorder: A complex diagnosis

E Timuçin Oral, MD Prof Psychiatry

Istanbul Commerce University Department of Psychology

X Aretaeus

X Hippocrates

X GalenX Soranus

Aretaeus of Cappadocia (AD 81–138)Early description of complex conditions

! Named diseases: – Diabetes (“a flowing through a siphon”) – Heterocrania/hemicrania (“half skull”) – Koiliakos (“coeliac disease”) !

! Defined phenomena: – Mania-melancholia – Bronchospasm – Asthma

Marneros & Goodwin,Cambridge University Press, 2005. Aydemir & Malhi, Acta Neuropsychiatrica. 2007:19;62

ARETAEUS of Cappadocia (fl. ca A.D. 50). Libri septem - RUFUS of Ephesus (fl. 1st century A.D.) De corporis humani partium appellationbus libri tres. in Latin by Junius Paulus Crassus (ca 1500-75). Venice: Giunta Press, 1552.

‘‘I think that melancholia is the beginning and a part of mania… The development of mania is really a worsening of the disease rather than a change into another... The symptoms [of melancholia] are not unclear: [the melancholics] are either quiet or dysphoric, sad or apathetic. Additionally, they could be angry without reason and suddenly awake in panic”

Aretaeus of Cappadocia (AD 81–138)

Marneros & Goodwin,Cambridge University Press, 2005

Problems in diagnosing BPD: “Cross-sectional & longitudinal”

Unipolar/bipolar depression? Mixed Symptoms

Problems in diagnosing BPD: “Cross-sectional evaluation”

Patients more likely to present with symptoms of depression

Symptom overlap

Depressive episodes and symptoms predominate in first-episode BD-I

Baldessarini Bipolar Disord. 2010;12:264. .

Time ill (%)

Morbidity from D-type symptoms is approximately 3 times greater

than from M-type symptoms

Judd 2002(n=146)

Post 2003 (n=258)

Joffe 2004 (n=138)

Paykel 2004(n=204)

Baldessarini 2010(n=303)

Overall, 5 studies (n=1049)

0 25 50 75 100

M-type (mania, hypomania, psychosis)

D-type (depression, dysthymia,dysphoric mixed states)Total

Total morbidity = 54%

Reclassifying major depressiveepisodes into a bipolar spectrum

Reclassification using Semi-structured Interview for Depression (SID) Cassano Psychopathology. 1989;22:278.

0,0

12,5

25,0

37,5

50,0

Bipolar I(n=25)

Bipolar II(n=107)

Bipolar III(n=5)

Recurrent depressive

(n=174)

Single episode(n=94)

33.8% bipolar spectrum

Patie

nts

(%)

SID subtype

Bipolar disorder in patients with a major depressive episode: BRIDGE study

DSM-IV criteria 16% (903 patients) met criteria

for bipolar disorder

Bipolar specifier 47% (2647 patients) met criteria

for bipolar disorder

Bipolar II disorderBipolar I disorderMDD

N=5635 Angst Arch Gen Psychiatry. 2011;68;791.

53%

Independent risk factors for bipolar disorder (DSM-IV-TR): BRIDGE study

Angst Arch Gen Psychiatry. 2011;68;791.903 patients with bipolar disorder (BP I: 685; BP II: 218)

≥2 Prior mood episodesHypomania/mania in first-degree relatives

Age at first psychiatric symptoms <30 yCurrent depressive episode ≤1 moMood lability with antidepressants

Current mixed stateCurrent psychotic featuresHistory of suicide attempts

Seasonality of mood episodesCurrent atypical depression

Current anxiety disorderBorderline personality disorderCurrent substance use disorder

FemaleManic/hypomanic with antidepressants

0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5

Odds ratio

Bipolar vs unipolar depression:differentiating characteristics

Bipolar UnipolarHistory of mania or hypomania Yes NoTemperament Cyclothymic DysthymicSex ratio Equal Women > menAge at onset Teens, 20s, and 30s 30s, 40s, 50sOnset of episode Often abrupt More insidiousNumber of episodes Numerous FewerPostpartum episodes More common Less commonPsychotic episodes More common Less commonPsychomotor activity Retardation > agitation Agitation > retardationSleep Hypersomnia > insomnia Insomnia > hypersomnia

Family history of BPD High LowFamily history of UPD High High

Adapted by Dunner D. with permission from: Akiskal J Affect Disord. 2005;84:107.

Melancholia, by Dürer Melancholia, by Cranach

Problems in diagnosing BPD: “Longitudinal evaluation”

Delayed diagnosisInitial diagnosis can take ≥10 years

Hirschfeld J Clin Psychiatry. 2003;64:161.

Biffin Acta Neuropsych. 2009;21:191.

10

20

30

40

50

60

70

80

Early AAO Intermediate AAO

DepressionMania

Freq

uenc

y (%

) P=0.001*

*Type of first episode (early AAO vs intermediate AAO) AAO, age at onset

Bipolar disorder: age at onset predicts initial polarity

72%

55.5%

(< 20 years) (20-39 years)


“Missed” diagnosis1/3 of patients are misdiagnosed

Hirschfeld J Clin Psychiatry. 2003;64:161.

Why is it important to get the diagnosis right?

! Misdiagnosis associated with ineffective treatment – worse outcome

! Potential risk of antidepressant switching ! Treatment approaches are different

Perlis Am J Manag Care. 2005;11:S271; Singh Psychiatry. 2006;3:57; Marcus Psychiatr Serv. 2009;60:617; Awad Prim Care Comp J Clin Psychiatry. 2007;9:195. !

.

Costs associated with potential misdiagnosis of bipolar disorder

Ann

ual d

irect

c

osts

per

pat

ient

(US$

200

4)

0

2500

5000

7500

10000

Potentially misdiagnosed (n=94) Correctly diagnosed (n=2398)

InpatientEmergency roomOutpatientPharmacy

Kamat AMCP. 2007.

54%

30%

P<0.01

Psychotic symptoms Mixed symptoms


Altınbaş Nöropsikiyatri Arşivi. 2011;48:167.

Bipolar II

Cyclothymia

Subclinical BP

Bipolar I Schizoaffective disorder, Bipolar

Schizophrenia

Minor depression

Major depression

Schizophrenia

Schizoaffective disorder, Depressive

Lifetime Mania

Lifetime Depression

Lifetime Psychosis

Proposed three-dimensional model of mood-psychotic disorders

Painting “Mania"

Florencio YllanaRybakowski J Affect Disord. 2011;128:319.

Mixed states vs pure mania in the EMBLEM study: outcome at 24 months

Azorin BMC Psychiatry. 2009;9:33.Based on 771 French patients followed for 24 months; *P=0.006

0

18

35

53

70

Relapse Recurrence Remission Recovery

Pure mania Mixed episodes

Patie

nts

(%)

*

Residual symptoms


Subthreshold depressive symptoms in bipolar, unipolar and healthy subjects in remission

50

Depressed mood

Gastrointestin

al symptom

***

*P<0.05; ***P<0.000 Vieta J Affect Disord. 2008;107:169.

Patie

nts

(%)

Healthy controlBipolar disorder

40

30

20

10

0

Feelings of guilt

Suicide

Insomnia early

Insomnia middle

Insomnia late

Work and activities

Retardation

Agitation

Psychic anxiety

Somatic anxiety

Somatic symptoms

Genital symptoms

Hypochondriasis

Insight

Loss of weight

17-Item Hamilton Depression Rating Scale

*

*

MDD

Progression from unipolar depression to bipolar disorder

550 patients with diagnosis of major depression followed for mean of 17.5 years

Number of subthreshold hypomanic symptoms associated with onset of threshold mania or hypomania

1.0

0.8

0.7

0.6

0.9

0.50 5 10 15 20 25 30

Years of Follow Up

Prop

ortio

n w

ithou

t hy

pom

ania

or m

ania

Time to either hypomania or maniaTime to hypomaniaTime to mania

Fiedorowicz Am J Psychiatry. 2011;168:40

Rapid cycling


Ineffective treatment = worse outcome, poor QoL

Rapid Cyclers(n=86)

Nonrapid Cyclers(n=872) p

Mean age at onset (years) 26.31±10.24 28.21±10.30 0.04

Mean delay (years) Symptom onset to current episode

20.38±11.88

15.90±10.92

0.0005

Illness progression, (%) Episodes with free intervals 59.3 72.6 0.009

Stressors (current episode), (%) 83.7 89.6 0.09

First episode polarity, (%) Depression 52.2 35.9 0.01

Mean previous episodes 19±16.54 7.09±6.40 <0.0001

Suicide attempts, (%) Lifetime (at least 1) Past year (at least 1)

44.2 14

37.6 6.5

0.22 0.01

Previous hospitalisations, (%) Multiple 10.5 4.5 0.004

Rapid cycling vs non-rapid cycling: course of illness

Azorin CNS Spectrum. 2008;13:780.

“Tree of Life”by Selen Şanlı

Comorbidities


Almost the rule

Severity, complications, worse outcome, poor QoL

Impaired psychosocial functioning

More severe disease course

Greater risk of depressive and mixed episodes, and suicidal

behaviour

Poorer treatment adherence

Decreased QoL

Comorbid condition

Possible earlier age

of onset

Complicates diagnosis and

treatment

Colom J Clin Psychiatry. 2000;61:549; Pollack Subst Abus. 2000;21:193; Vieta Bipolar Disord. 2001;3:253; Keller J Clin Psychiatry. 2006;67(suppl 1);5.

Comorbidities complicate diagnosis and management of bipolar disorder

0

18

35

53

70

No anxiety Anxiety

Polarity treated in acute phase

Tim

e to

rem

issi

ona (

wee

ks)

Manic Depressed Mixedn=23 n=7 n=24 n=18 n=11 n=9

Anxiety symptoms delay time to remission in patients with bipolar I disorder

Feske Am J Psychiatry. 2000;157:956.

aBased on Kaplan-Meier survival analysis; Anxiety-related correlates included history of panic attacks, diagnosis of lifetime threshold or sub-threshold anxiety disorder, baseline Hamilton Rating Scale for Depression (HAM-D) psychic and somatic anxiety

Log rank=4.37 df=1, P=0.04

Log rank=2.95 df=1, P=0.09

Log rank=1.45 df=1, P=0.29


Switching

“Illusion of Rising”by Tamer Ertuna

Revised DSM-5 criteria for mood disorder Mixed features

! Full criteria for manic or hypomanic episode, plus 2–3 of the following symptoms nearly every day for at least1 week:

– Depressed/down – Decreased interest or pleasure – Psychomotor retardation – Fatigue – Worthlessness/guilt – Death/suicide

! Full criteria for major depressive episode, plus 2–3 of the following nearly every day for at least 1 week

– Expansive or irritable – Grandiose – Increased/pressured speech – Flight of ideas – Increased/excessive involvement

in activities with high potential for painful consequences

– Increased goal-directed activity – Increased energy – Decreased need for sleep

American Psychiatric Association. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=428. Accessed April 20, 2010.

Bipolar disorder: a complex diagnosis

Bipolar disorder: a complex diagnosis

Cognitive symptoms ! Racing thoughts ! Distractability ! Disorganisation ! Inattentiveness

Dysphoric or negative mood and behaviour ! Depression ! Anxiety ! Irritability ! Hostility ! Violence or suicide

Psychotic symptoms ! Delusions ! Hallucinations

Manic mood and behaviour ! Delusions ! Euphoria ! Grandiosity ! Pressured speech ! Impulsivity ! Excessive libido ! Recklessness ! Social intrusiveness ! Diminished need for sleep

Summary! Bipolar disorder is a chronic, frequent and

debilitating illness

! Although it is one of the well- and first-known disorders, it is still misdiagnosed frequently

! Appropriate diagnosis is the first step in choosing the best treatment available

! Rational psychopharmacology is a sine qua non for prevention and is possible

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Bipolar a complex disorder

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