CLASSIFICATION OF BIPOLAR AFFECTIVE DISORDERS

Chairperson: Dr. K. KrishnamurthyPresenter: Dr. Wilona

Introduction

• Mood disorders are among the most frequent psychiatric illnesses both in the community and in psychiatric settings

• Patients commonly present with features of either mania or depression and sometimes both

• These disorders virtually always result in impaired interpersonal, social, and occupational functioning

Introduction

• After relative neglect in the age of melancholy during the 1970s and 1980s there has been a renaissance of bipolar disorder during the last decade of the 20th century

• Recent survey of the members of the depressive and Manic- Depressive Association in the united states found that early misdiagnosis was common, and often a decade elapsed before the correct diagnosis

Introduction

• The signs and symptoms of the classical cyclical illness are unmistakable

• However, very often an insiduous onset or subthreshold symptoms may present a diagnostic challenge

• What has emerged from recent studies is that bipolar disorders consist of a group of overlapping clinical sub-types

History

A state of raving madness with exalted mood – GreeksHippocrates Used the term “mania and melancholia” to describe mental illness. Believed that the illness often arose from the substrate of the melancholic temperaments, which under the influence of planet Saturn made the spleen secrete black bile, ultimately leading to mood darkening , through its influence on the brain.

History Aulus Corneleus described melancholia as depression caused by black bile.Bonet described a mental illness called manico melancholicus.Soranus described mania as remitting illness which in some patients had a admixture of melancholia: continual wakefulness, and fluctuating states of anger and merriment, sometimes of sadness and futility during the same episode

HistoryAretaeus of Cappadocia is credited with explicitly stating the connection between the two major mood states and described the cardinal features of mania.States that melancholy is the commencement and a part of maniaMania- a disease of adolescent & young men given intermittently to “active habits, drunkenness & lechery”Also reported of secondary personality changesExacerbation more frequent in spring

HistoryJules Falret coined ‘ folie circulaire’ – described patient who became depressed and elated in cyclic fashion.Jules Baillarger coined ‘folie a double forme, - in which the patients became deeply depressed and feel into a stupurous state from which he would eventually recover.Karl Ludwig Kahlaum The episodes of mania and melancholia were different stages of the same disease process, called cyclothymia.

HistoryEmil Kraeplin Grouped mania & melancholia together Concluded that all of the mood disorder are identical in certain ways , this formulation of a single underlying disorder was widely accepted for several decades. Also termed the involutional melancholia Observed that manic depressive psychosis was a separate entity from schizophrenia.

History

Kraeplins principle• Various forms had a common heredity• Frequent transitions from depression to mania or vice versa• Superimposed episodes opposite to habitual temperaments• Depression and manic episodes could intermix during the same episode• Recurrent course with illness free intervals

Kraeplins Concept of mixed states in contemporary practice.

Type of mixed state mood thinking activity

Anxious depressive mania

Excited depression

Depression with flight of ideas

History

Karl Abraham • accepted Kraeplins notion of single mood illness.Sigmund Freud• emphasized the importance of loss in depression.• Anger is turned inwards in depressed individuals• Determined that some depression are psychogenic and others are biological.

History Unipolar – bipolar distinctionThe proposal to divide manic depressive illness into separate bipolar and unipolar first brought by Leonhard. Angst produced convincing evidence Perris showed that bipolar started on an average fifteen years earlier than depression and recurred more frequently

HistoryHenry Maudsley coined the term affective disorderPope Lipinski explained schizophrenia symptoms in manic depressive psychosisAkiskal - 1983 broadened the bipolar spectrum.

Contemporary classificatory approaches

Unipolar – Bipolar Distinction • Many researchers working independently in

different continents found there is a difference between Unipolar and Bipolar depression

• Observation in past two decades have found an overlap between those extremes – Pseudo-unipolar

Differences between the twoFeature Bipolar Unipolar

Mania /Hypomania

Present Absent

Sex ratio Equal More in women

Age at onset Teens, 20’s,30’s 30’s,40’s,50’s

Post partum episodes More common Less common

Onset of episode Often abrupt More insidious

Anti depressants Induced hypomania/Mania

Rare

Lithium Acute Anti depressant effect

Generally ineffective

Probabilistic approachUnipolar depression more likely if ≥ 4 Bipolar depression more likely if ≥ 4

Symptomatology

Insomnia Hypersomnia

Decreased appetite Hyperphagia

Psychomotor agitation Psychomotor retardation

Other atypical symptoms

Somatic complaints Psychosis and/ or pathological guilt

Mood lability or manic symptoms

Course of illness

Later onset > 25 yrs Earlier onset < 25 yrs

Long current depression > 6 months Multiple depressions ≥ 5 episodes

Family history

No bipolar disorder Bipolar disorder

Proposed by Task Force on Diagnostic Guidelines of the International Society For Bipolar Disorders

The overlap

• Firstly there are depressive patients who experience very brief hypomanic episodes

• Secondly 10-20% patients with MDD subsequently develop hypo or manic episodes and have to reclassified bipolar I or II . Average latency of 6 years noticed from first depressive episode

• Thirdly there are unipolar patients in Bipolar Pedigree – common genetic linkage

So…

• This overlap explains why some apparently unipolar patients respond to lithium monotherapy or augmentation

• Kraeplin declared that the illness pursued an indefinite number of courses but he was sceptical of subdivisions since it would undermine his concept of manic depressive illness

• The question is whether there are validated clinical subtypes ?

Bipolar Subtypes - general

• Bipolar I• Bipolar II• Bipolar III• Bipolar IV

Bipolar I

• Teenage years the 20s or 30s • First episode can be manic, depressive or

mixed• Common mode of onset is mild retarded

depression or hypersomnia for few weeks or months which often switches to manic episode

• In others several depressive episodes occur before first mania

• Secondary manias – occur in association with cerebral, endocrine, and other systemic medical conditions. Irritable mood prevails

Bipolar II• Typically present with MDD and upon enquiry

history of hypomanic episodes elicited• Rates were underestimated till recently• Documenting hypomania among subjects

suspected of cyclothymia• Complexity is less severe symptom intensity

but more severe course• Mood lability is a most specific predictor for

switch• Diagnosis is crucial for prognosis • High suicidality

Bipolar III• Antidepressant mobilised switch• These hypomanic episodes are somewhat milder and

less likely with SSRI than TCA• MAOI induce euphoric while TCA induce dysphoric

hypomania• Probing may reveal hypomanic episodes in the past• Can occur in patients with dysthymia as well as ocd,

social phobia and panic disorders

Bipolar IV

• Experience cycles of depression and hyperthymia

• Hyperthymia is characterised by lifelong traits of upbeat, energy driven and overconfident disposition

• Hyperthymic traits precede manic episodes

Klerman classification

• Bipolar I - same• Bipolar II – same • Bipolar III – Cyclothymia• Bipolar IV – Hypomania or mania precipitated by

medication• Bipolar V – Depressed patient with Bipolar relatives• Bipolar VI – Mania without Depression

Cyclothymia • Individuals In whom Low grade affective

manifestations of a subdepressive and mild hypomanic nature oscillated over long periods of life span

• Could occur throughout life without progression to major affective episodes and if episodes do occur they return to their cyclothymic baseline

• Biphasic shifts lasts typically no more than a few days

• Strong familial association with Bipolar disorder. Linked more to Bipolar II than I

• Occurs in 6% of general population

Are there only 4 or 6 subtypes?

• A strong case can be made for Bipolar I, II, III, IV. However Kraeplin after charting 18 patterns of affective phases in his large manic-depressive sample found that there were so many other patterns that the task of delineating specific course patterns could not be achieved

• Therefore Akiskal brought about the intermediary subtypes

Akiskal classification

• Bipolar I: full blown mania-manic depressive illness has an explosive manic

onset with psychosis while some have mixture of depression and mania

Bipolar I1/2

• Depression with protracted hypomania-where hypomania ends and mania starts is not clearly

demarcated-patients exist between these extremes with protracted

hypomanic periods which cause some trouble to the patient and significant others without reaching the destructive potential of mania

Bipolar II• Depression with hypomania-moderately to severely impairing major depressions,

interspersed with hypomanic periods of at least 4 days duration without marked impairment

-signs and symptoms of hypomanic episode represent a departure from the patients habitual baseline

-although behavior is colored by elated mood, confidence and optimism ,judgement is relatively preserved compared with mania

- The cyclic mood changes permit normal to supernormal periods of functioning

- A considerable number of patients are able to rebound from their difficult periods to attain new conjugal or occupational status – sunny bipolar IIs

Bipolar II 1/2

• Cyclothymic depressions- Many soft bipolar patients do not meet criteria for

Bipolar II due hypomanic episodes being in range of 1 to 3 days compared to criteria which exists for 4 days

- Patients with short hypomania often have a recurrent pattern of periods of excitement which are followed by minidepressions thereby fulfilling criteria for cyclothymia

- When a major depressive episode is superimposed on this baseline , the diagnosis of bipolar may be completely missed because the instability in the life of a cyclothymic may be of such a degree that these patients meet criteria for axis II cluster B personality disorder at the trait level

- They are more prone to be labelled borderline than affectively ill

- Mood lability represents the most powerful predictor of which depressive patient would develop frank hypomania

- The mood lability in this bipolar shown that most cyclothymic individuals do not exhibit clearcut hypomanic features but instead give evidence of depressive moodiness characterised by brief depressive mood swings . Such moodiness unfortunately gets classified as borderline personality by DSM IV

Bipolar III

• Antidepressant associated hypomania

Bipolar III 1/2• Bipolarity masked – and unmasked- by

stimulant abuse- Patients whose periods of excitement are so

closely linked with substance or alcohol use and abuse that it is not always easy to decide whether these periods would have occurred in the absence of such use or abuse

- Possible benefit of mood stabilisation is given to these patients who would otherwise be classified as substance induced or withdrawal induced mood disorders

Bipolar IV

• Hyperthymic depression- Clinical depression that occurs later in

life and superimposed on a lifelong hyperthymic temperament

- Many hyperthymics seem protected from depression and if they succumb it is usually later in life

- Variant is a pattern whereby the temperament lead to a great deal of trouble in their lives often associated with recurrent depression

- When hyperthymic individuals become depressed the initial episode is hypersomnic retarded

- The use of antidepressants tends to destabilise the underlying hyperthymic temperament

- Eventually the elements of temperament appear in the depression include increased sexuality and racing thoughts these are depressive mixed states

- Hence patients who meet criteria for MDD plus have intrusions of hypomanic signs and symptoms – ‘excited depressives’

A proposed broad spectrum of bipolar disorders by Akiskal and Pinto.

• ¼ unstable form of unipolar depression, responding rapidly but in unsustained manner to antidepressants

• ½ schizobipolar disorder• I manic depressive illness• I ½ depression with protracted hypomania

• II depression with spontaneous discrete hypomanic episodes

• II ½ depression superimposed on cyclothymia

• III depression + hypomania occurring in association with anti depressants or other somatic treatment

• III ½ prominent mood swings association with substance &/or alcohol abuse.

• IV depression superimposed on hyperthymia.

• V recurrent depressions that are admixed with dysphoric hypomania

• VI late onset depression with mixed mood features, progressing to a dementia like syndrome

ICD 10 classification• F31.0 BPAD, current episode hypomanic• F31.1 BPAD, current episode manic without psychotic

symptoms• F31.2 BPAD, current episode manic with psychotic

symptoms• F31.3 BPAD, current episode mild or moderate

depression .30 without somatic syndrome .31 with somatic syndrome

• F31.4 BPAD, current episode severe depression without psychotic symptoms

• F31.5 BPAD, current episode severe depression with psychotic symptoms

• F31.6 BPAD, current episode mixed• F31.7 BPAD, currently in remission• F31.8 Other BPAD• F31.9 BPAD, unspecified

Evolution of bipolar in DSM

• DSM-III(1980) - the term 'bipolar disorder' replaced the older term 'manic depressive disorder'. Also, the diagnostic distinction between adult and pediatric bipolar disorder was indicated for the first time.

• In the DSM-III-R (1987)- diagnoses supplemented with subtyping classifications such as

- Bipolar Disorder-Mixed- Bipolar Disorder-Manic- Bipolar Disorder-Depressed - Bipolar Disorder-Not Otherwise Specified - Cyclothymia.

• DSM-IV (1994) and DSM-IV TR-The definition of bipolar disorders has evolved from a monolithic disorder with a single set of criteria, to a more nuanced subtype system, where Bipolar I and Bipolar II forms of the disorder are recognized and differentiated

DSM IV TR classification• Bipolar disorders 296.XX Bipolar I Disorder .0X Single Manic EpisodeSpecify if: Mixed

.40 Most recent episode Hypomanic .4X Most recent episode Manic .6X Most recent episode Mixed .5X Most recent episode Depressed .7 Most recent episode Unspecified

296.89 Bipolar II Disorder Specify (current or most recent episode) : Hypomanic / Depressed

301.13 Cyclothymic Disorder296.80 Bipolar Disorder NOS

Prevalence rate – lifetime prevalence rates

• Bipolar I – 0 – 2.4%• Bipolar II – 0.3 – 4.8%• Cyclothymia – 0.5 – 6.8 % • Hypomania – 2.6 – 7.8%• Full term spectrum – 2.6% - 7.8%

BARCELONA INTERNATIONAL “CONSENSUS” ON BIPOLAR SUB-TYPES BEYOND DSM IV AND ICD 10.

• Mood incongruent bipolar psychosis• Bipolar I (mania)• Mixed mania (>/= 2 depressive symptoms)• Bipolar II (hypomania >/= 2 days)• Somatic treatment induced hypomania• Rapid cycling• Cyclothymia• Recurrent brief hypomania

The Controversies

• The unipolar-bipolar distinction left undefined many affective conditions lying between ,which are encountered in pedigrees of bipolar probands

• Based on clinical intuition it was argued that ‘phenotypically’ Unipolar relatives of bipolar probands are ‘genotypically’ Bipolar

• Hence 4 – 5% of general population belongs to broad bipolar spectrum with predominantly depressive phenomenology and muted bipolar features

• Dunner et al - identified these less than manic patients as bipolar II

• Diagnosis of Bipolar I for those requiring hospitalisation – whether it can be a criteria?

• Akiskal and Mallya – ‘soft Bipolar Spectrum’• How to subdivide the broad clinical terrain of

bipolarity on genetic terms?• Cassano et al argue that bipolar spectrum is a

clinical reality but in search of diagnosis and assessment methodology

DSM Vs ICD concepts• Unipolar disorder is avoided because of risk of

conversion to bipolar• ICD 10 is less committed to the concept of spectrum• Cyclothymia recognised with bipolar in DSM while

classified with dysthymia under persistent affective disorder in ICD 10

• ICD 10 does not recognise Bipolar II as a category but an example of nondescript ‘other’ category

• ICD allows RDD to be diagnosed inspite of hypomanic episodes during recovery

• Both don’t include antidepressant induced switch in bipolar rubric

• Both accept mixed states• ICD does not have provision for rapid cycling

though

Overall

• ICD 10 definition of bipolar phases and subtypes pay greater attention to phenomenology and less attention to arbitrary cut offs on the number of symptoms and their duration with which DSM IV is burdened

DSM 5 and Bipolar disorder

• There have been proposals to include further and more accurate subtyping for bipolar disorder (Akiskal and Ghaemi, 2006)

• More stringent criteria for the diagnosis of bipolar disorder in children. A new diagnosis Temper Dysregulation Disorder with Dysphoria proposed

Conclusions • The clinical phenomenology of bipolar subtypes

has remissions and exacerbations and it is not possible to divorce the clinical picture from treatments received

• As practising clinicians extending the concept of bipolar spectrum to include what others might consider unipolar territory, substance abuse or axis II pathology would help in the cause of shielding these patients from possible negative effects of antidepressants unprotected by mood stabilisers

Conclusions

• But there are many controversies regarding this and many researchers may not agree with these

• The literature is got from patients who are not representative of patients seen in contemporary clinical practise

• The challenge is to make sense of this larger universe of patients who do not become research subjects