Bipolar Disorder

JOURNAL CLUBJOURNAL CLUB

CALMING THE BIPOLAR STORMCALMING THE BIPOLAR STORM

EPIDEMIOLOGY OF BIOPLAR-1EPIDEMIOLOGY OF BIOPLAR-1

4% OF GENERAL POPULATION 4% OF GENERAL POPULATION SUFFERS FROM BIPOLAR DISORDERSUFFERS FROM BIPOLAR DISORDER

AMONG 18-44 YEARS THE PREVALNCE AMONG 18-44 YEARS THE PREVALNCE IS 6 %IS 6 %

HOSPITAL ADMISSIONHOSPITAL ADMISSION

40% FOR MIXED STATES40% FOR MIXED STATES

25% FOR RAPID CYCLER25% FOR RAPID CYCLER

EPIDEMIOLOGY OF BIOPLAR-2EPIDEMIOLOGY OF BIOPLAR-2

80% OF CASES OF BIPOLAR REMAINS 80% OF CASES OF BIPOLAR REMAINS UNDIAGNOSED OR MISDIAGNOSEDUNDIAGNOSED OR MISDIAGNOSED

MISDIAGNOSIS OF THE BIPOLAR IS A MISDIAGNOSIS OF THE BIPOLAR IS A SERIOUS PROBLMSERIOUS PROBLM

- USUALLY ARE MISDIAGNOSED AS A - USUALLY ARE MISDIAGNOSED AS A UNIPOLAR DEPRESSIONUNIPOLAR DEPRESSION

- ARE GIVEN AN ANTIDEPRESSANT - ARE GIVEN AN ANTIDEPRESSANT WITHOUT A MOOD STABILIZERWITHOUT A MOOD STABILIZER

- CAN WORSEN DISORDER BY INDUCING - CAN WORSEN DISORDER BY INDUCING MANIA AND/OR MIXED MANIC SYMPTOMSMANIA AND/OR MIXED MANIC SYMPTOMS

SYMPTOMS SUGGESTIVE OF SYMPTOMS SUGGESTIVE OF BIPOLAR DISORDERBIPOLAR DISORDER

EARLEY ONSET DEPRESSIONEARLEY ONSET DEPRESSION FREQUENT EPISODESFREQUENT EPISODES POOR OR IDIOSYNCRATIC RESPONSE TO ANTIDEPRESSANTPOOR OR IDIOSYNCRATIC RESPONSE TO ANTIDEPRESSANT THE COURSE AND PRESENTATION OF DEPRESSION THE COURSE AND PRESENTATION OF DEPRESSION

CHANGES OVER TIME; FOR EXAMPLE THEY ARE CHANGES OVER TIME; FOR EXAMPLE THEY ARE PSYCHOMOTOR RETARDED AT ONE POINT AND AGITATED AT PSYCHOMOTOR RETARDED AT ONE POINT AND AGITATED AT ANOTHERANOTHER

DEPRESSION/ANXIETY ARE COMBINED WITH SUBSTANCE DEPRESSION/ANXIETY ARE COMBINED WITH SUBSTANCE ABUSEABUSE

DEPRESSION/ANXIETY ARE COMBINED WITH IMPULSIVITYDEPRESSION/ANXIETY ARE COMBINED WITH IMPULSIVITY CHILDHOOD ONSET OF A MOOD DISORDERCHILDHOOD ONSET OF A MOOD DISORDER EARLY ONSET PSYCHOSIS WITH GOOD SOCIAL FUNCTIONEARLY ONSET PSYCHOSIS WITH GOOD SOCIAL FUNCTION FAMILY HISTORY OF MOOD/SUBSTANCE ABUSE PROBLEMFAMILY HISTORY OF MOOD/SUBSTANCE ABUSE PROBLEM

MIXED BIPOLAR EPISODE-MIXED BIPOLAR EPISODE-INCIDENCEINCIDENCE

Several studies were done to determine Several studies were done to determine the incidence rate of mixed bipolar the incidence rate of mixed bipolar episodesepisodes

The incidence rate ranges between 40% The incidence rate ranges between 40% and 57% of bipolar patientsand 57% of bipolar patients

MIXED BIPOLAR EPISODE-SYMPTOMSMIXED BIPOLAR EPISODE-SYMPTOMS

MIXED BIPOLAR EPISODE-MIXED BIPOLAR EPISODE-SYMPTOMSSYMPTOMS

DSM-IV Criteria for Mixed Bipolar EpisodeDSM-IV Criteria for Mixed Bipolar Episode Meets criteria A of Major Depressive Episode Meets criteria A of Major Depressive Episode

and B of Manic Episode for at least one weekand B of Manic Episode for at least one week Mixed episodes are those where patients Mixed episodes are those where patients

experience both depressive and experience both depressive and manic/hypomanic episodemanic/hypomanic episode

There may be variability of mixed state There may be variability of mixed state symptoms in the same individualsymptoms in the same individual

There can be possible predominance of either There can be possible predominance of either depressive or manic symptoms over time in the depressive or manic symptoms over time in the same individualsame individual

MIXED BIPOLAR EPISODE-MIXED BIPOLAR EPISODE-SYMPTOMSSYMPTOMS

The symptoms like irritability, anxiety, The symptoms like irritability, anxiety, dysphoric mood, and agitation can be dysphoric mood, and agitation can be common symptom in the bipolar patientcommon symptom in the bipolar patient

These symptoms should raise the index of These symptoms should raise the index of suspicion that the patient is in a mixed suspicion that the patient is in a mixed statestate

Life charts are valuable in recognizing and Life charts are valuable in recognizing and managing the most challenging bipolar managing the most challenging bipolar patientpatient

COURSE OF MIXED BIPOLARCOURSE OF MIXED BIPOLAR

Patients with mixed episode has a more severe Patients with mixed episode has a more severe course than those with classic euphoric maniacourse than those with classic euphoric mania

Less frequent remissionsLess frequent remissions Higher rates of recurrenceHigher rates of recurrence More frequent substance abuseMore frequent substance abuse Poorer response to some medicationsPoorer response to some medications More extensive co morbiditiesMore extensive co morbidities Increased potential for suicidal tendenciesIncreased potential for suicidal tendencies

STRATEGIES FOR THE STRATEGIES FOR THE TREATMENT OF BIPOLAR TREATMENT OF BIPOLAR

DISORDERDISORDER

Most bipolar need Most bipolar need medications for their medications for their whole lifewhole life

Tolerability and Tolerability and treatment adherence treatment adherence are essential because are essential because of thatof that

STRATEGIES FOR THE TREATMENT OF BIPOLAR STRATEGIES FOR THE TREATMENT OF BIPOLAR DISORDERDISORDER


DISORDERDISORDERFirst start treatment with agents of proven First start treatment with agents of proven

efficacyefficacyAdequate dose of the drugs must be usedAdequate dose of the drugs must be usedSometimes combination treatment can Sometimes combination treatment can

lower the dose of the single agentlower the dose of the single agentFamiliarize with new agents and consider Familiarize with new agents and consider

them based on evidence and feasibilitythem based on evidence and feasibilityCollaborate with psychosocial or medical Collaborate with psychosocial or medical

standpointstandpoint


DISORDERDISORDEROnce a dose and depot preparation for Once a dose and depot preparation for

atypicals can enhance the compliance of atypicals can enhance the compliance of the medicationthe medication

Data are limited for usefulness of ECT in Data are limited for usefulness of ECT in acute maniaacute mania

Some studies have found ECT as effective Some studies have found ECT as effective as atypical antipsychotic in the treatment as atypical antipsychotic in the treatment of maniaof mania

MEDICATIONS MEDICATIONS ACUTE MANIAACUTE MANIA MAINT.MAINT. AC. DEPRESS.AC. DEPRESS.

LithiumLithium LithiumLithium Olanazapine-Olanazapine-fluoxetine combfluoxetine comb

ChlorpromazineChlorpromazine LamotrigineLamotrigine

DivalporexDivalporex OlanazapineOlanazapine

OlanazapineOlanazapine AripiprazoleAripiprazole

RisperidoneRisperidone

QuetiapineQuetiapine

ZiprasidoneZiprasidone

AripiprazoleAripiprazole

CarbamazepineCarbamazepine

FDA APPROVED BIPOLAR FDA APPROVED BIPOLAR TREATMENT OPTION-MOOD TREATMENT OPTION-MOOD

STABILIZERSTABILIZER

MANIAMANIA MIXED MIXED MAINT.MAINT. DEPRESDEPRES

LITHIUMLITHIUM ++ -- - - --

DivalproDivalpro ++ -- -- --

DivaER/DivaER/Carb ERCarb ER

++ ++ __ __

LamotriLamotri __ _ _ ++ __

FDA APPROVED BIPOLAR FDA APPROVED BIPOLAR TREATMENT OPTION-antipsychTREATMENT OPTION-antipsych

MANICMANIC MIXEDMIXED MAINT.MAINT. DEPRESDEPRES

OlanazaOlanazapinepine

++ ++ + + __

RisperiRisperi ++ ++ __ __

QuetiaQuetia ++ __ __ __

ZiprasidZiprasid ++ ++ __ __

AripipraAripipra ++ ++ ++ __

FDA APPROVED BIPOLAR FDA APPROVED BIPOLAR TREATMENT OPTION-otherTREATMENT OPTION-other

ManiaMania MixedMixed MainteMainte DepreDepre

Olanaza/Olanaza/

FluoxetinFluoxetin

__ __ __ ++

Consensus Guidelines: Initial Consensus Guidelines: Initial Treatment Regimen Bipolar ITreatment Regimen Bipolar I

Clinical Clinical

PresentationPresentation

Preferred InitialPreferred Initial

StrategiesStrategies

AlternateAlternate


Euphoric maniaEuphoric mania MS aloneMS alone

MS + APMS + AP

Add a BZD to other Add a BZD to other agentsagents

AP aloneAP alone

Dysphoric mania or Dysphoric mania or true mixed maniatrue mixed mania

MS + APMS + AP

MS aloneMS alone

Add BZD to either Add BZD to either agentagent

AP aloneAP alone

Combination of two Combination of two MSMS

Mania with history of Mania with history of rapid cyclingrapid cycling

MS + APMS + AP

MS aloneMS alone

Combination of two Combination of two MSMS

Add a BZD to either Add a BZD to either agentagent

AP aloneAP alone

Mania with Mania with psychosispsychosis

MS + APMS + AP

AP aloneAP alone

Add BZD to either Add BZD to either agentagent

MS aloneMS alone

Consensus Guidelines: Inadequate Consensus Guidelines: Inadequate Response to Initial TreatmentResponse to Initial Treatment

InitialInitial

TreatmentTreatment

Preferred Preferred


Alternate Alternate


MonotherapyMonotherapy

With a MSWith a MS

Add an AAPAdd an AAP

Add a different MSAdd a different MS

Monotherapy Monotherapy

With an AAPWith an AAP

Add a MSAdd a MS Switch to a MSSwitch to a MS

MS + AAPMS + AAP Replace the current Replace the current AAP with a different AAP with a different AAPAAP

Add different MSAdd different MS

Replace the MS with Replace the MS with different MSdifferent MS

TREATMENT OF MANIATREATMENT OF MANIALithium and AnticonvulsantLithium and Anticonvulsant

ACUTEACUTE ACUTEACUTE ACUTEACUTE MAINT.MAINT.

DRUGDRUG ADULT ADULT DOSE/DOSE/

DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

LithiumLithium Level ofLevel of

1.2 1.2 mEq/lmEq/l

300-900 300-900 mgmg

0.8-1.2 0.8-1.2 mEq/LmEq/L

++++




DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

DVPDVP Oral loadOral load

30 30 mg/kg/dmg/kg/d

250-500 250-500 HS for 2 HS for 2 daysdays

125 125 microgramicrogra/ml/ml

++++




DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

DVP ERDVP ER Oral loadOral load


750 750 mg/daymg/day


__




DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

DVPDVP Oral loadOral load


250-500 250-500 HS for 2 HS for 2 daysdays


++++




DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

CBZCBZ 800-800-1000mg1000mg

200 mg 200 mg HS, BID HS, BID or TIDor TID


++




DAYDAY

STARTSTART

DOSEDOSE

MAX.MAX.

DOSEDOSE

EFFICAEFFICA

IN IN MAINTEMAINTE

CBZ ERCBZ ER 800-800-1000mg1000mg



++


Lamotrigine ( LTG )Lamotrigine ( LTG )

Not recommended for acute Not recommended for acute maniamania

TREATMENT OF MANIA: TREATMENT OF MANIA: ANTIPSYCHOTIC DOSINGANTIPSYCHOTIC DOSING

AcuteAcute AcuteAcute AcuteAcute Mainten.Mainten.

DrugDrug Adult Adult dose/daydose/day

Starting Starting DoseDose

Max. Max. Rec. Rec. DosesDoses

Efficacy Efficacy

In Maint.In Maint.

TxTx

AripripraAripriprazolezole

15-30 15-30 mgmg

5-15 5-15 m/daym/day

30 mg30 mg






Efficacy Efficacy

In Maint.In Maint.

TxTx

ClozCloz 100-900 100-900 QD or QD or BIDBID

12.5-25 12.5-25 mg BIDmg BID

30 mg30 mg ++






Efficacy Efficacy

In Maint.In Maint.

TxTx

OLZOLZ 15-30 15-30 mg QD mg QD or BIDor BID

5-10 mg 5-10 mg HS; also HS; also 40 mg 40 mg disdis

40 mg40 mg ++++






Efficacy Efficacy

In Maint.In Maint.

TxTx

QuetiQueti 400-800 400-800 mg QD mg QD or BIDor BID

25-200 25-200 mg HSmg HS

800 mg800 mg __






Efficacy Efficacy

In Maint.In Maint.

TxTx

RisRis 1-6 mg1-6 mg 6 mg6 mg __






Efficacy Efficacy

In Maint.In Maint.

TxTx

ZipZip 40-160 40-160 mg QD mg QD or BIDor BID

20-40 20-40 mg BIDmg BID

160 mg160 mg __

Tolerability of Bipolar agentsTolerability of Bipolar agentsOther than antipsychoticsOther than antipsychotics

DrugsDrugs Weight Weight gaingain

CNSCNS EPSEPS DermDerm GIGI

LithiumLithium ++++ ++++++ 00 ++++ ++++++

DivalopDivaloprexrex

++++ ++++ 00 ++ ++++

CabamCabamazepinazepin

++ ++++++ 00 ++++++ ++++

LamotriLamotrigenegene

++ ++ 00 ++++ ==

Consensus Guidelines: Inadequate Consensus Guidelines: Inadequate Response to Initial TreatmentResponse to Initial Treatment

Optimize dose of initial therapy Optimize dose of initial therapy (foundation therapy) before (foundation therapy) before making changemaking change

GUIDELINES FOR MEDICATIONSGUIDELINES FOR MEDICATIONSIN BIPOLAR-1IN BIPOLAR-1

Patient should be taking a therapeutic Patient should be taking a therapeutic dose of a mood stabilizer and that mood dose of a mood stabilizer and that mood stabilizer should be maximized before stabilizer should be maximized before prescribing an antidepressantprescribing an antidepressant


Combinations of mood stabilizers be Combinations of mood stabilizers be should be considered as well. If the first should be considered as well. If the first mood stabilizer does not work, consider mood stabilizer does not work, consider adding a second oneadding a second one

Addition of lithium should be considered in Addition of lithium should be considered in patients failing to respond adequately to patients failing to respond adequately to these initial responsethese initial response


For classical euphoric and dysphoric and For classical euphoric and dysphoric and mixed mania and rapid cycling:mixed mania and rapid cycling:

Use a mood stabilizer alone or a mood Use a mood stabilizer alone or a mood stabilizer with an atypical are considered stabilizer with an atypical are considered an appropriate first or second line of an appropriate first or second line of treatmenttreatment


Treat psychosis properlyTreat psychosis properly

A good core mood stabilizer, even in face A good core mood stabilizer, even in face of psychosis, should treat the whole of psychosis, should treat the whole affective syndromeaffective syndrome

If the patient failed to respond to initial If the patient failed to respond to initial treatment with a monotherapy with a mood treatment with a monotherapy with a mood stabilizer, add an atypical or add a stabilizer, add an atypical or add a different mood stabilizerdifferent mood stabilizer

Until the patient is clearly on a standard Until the patient is clearly on a standard mood stabilizer, antidepressant should not mood stabilizer, antidepressant should not be consideredbe considered

If using anticonvulsants, it is important to If using anticonvulsants, it is important to ensure that the patient is at a therapeutic ensure that the patient is at a therapeutic dose determined by blood level before dose determined by blood level before declaring the failuredeclaring the failure

Measure lithium level to assess adequate Measure lithium level to assess adequate dosingdosing

GUIDELINES FOR TREATMENT GUIDELINES FOR TREATMENT OF BIPOLAR DISORDEROF BIPOLAR DISORDER

Identify and manage symptoms that Identify and manage symptoms that destabilize illnessdestabilize illness

1. Sleep disturbance1. Sleep disturbance2. Anxiety2. Anxiety3. Psychosocial stressors3. Psychosocial stressors4. Co-morbid condition4. Co-morbid condition


Restore psychosocial functioningRestore psychosocial functioning

Educate patient and significant othersEducate patient and significant others

Monitor patient and recognize that the course may Monitor patient and recognize that the course may change over timechange over time

Utilize life chartingUtilize life charting


Accurate diagnosis-remission and ultimate Accurate diagnosis-remission and ultimate recoveryrecovery

Treat entire illness, not just episodeTreat entire illness, not just episode

Individual treatmentIndividual treatment

Explore aggressive treatment strategies (eg Explore aggressive treatment strategies (eg loading strategies, ER formulations )loading strategies, ER formulations )


Utilize medications that optimize efficacy, Utilize medications that optimize efficacy, safety, tolerability, and adherencesafety, tolerability, and adherence

- Maximize mood stabilizer, including Maximize mood stabilizer, including combination therapycombination therapy

- Use anxiolytics/hypnotics, atypical Use anxiolytics/hypnotics, atypical neuroleptics and novel anticonvulsants as neuroleptics and novel anticonvulsants as adjunctive therapy to mood stabilizeradjunctive therapy to mood stabilizer

- Use brief, acute, intermittent Use brief, acute, intermittent antidepressant therapyantidepressant therapy

COMBINATION COMBINATION TREATMENTTREATMENT

Predictors for potential need for combination Predictors for potential need for combination therapytherapy....

-Acute mania-Acute mania-Mixed states-Mixed states-Depressive components-Depressive components-Rapid cycling-Rapid cycling-Psychosis-Psychosis-Severity of illness-Severity of illness-Increasing age-Increasing age-Prior hospitalization-Prior hospitalization


Commonly effective combination therapyCommonly effective combination therapy1. Lithium plus divalproex1. Lithium plus divalproex2. an atypical plus lithium/divalproex2. an atypical plus lithium/divalproex3. an antipsychotic plus divalproex3. an antipsychotic plus divalproex


Once the patient is stabilized, it becomes Once the patient is stabilized, it becomes more important to look at what treatments more important to look at what treatments may not be playing such an important rolemay not be playing such an important role

Combination therapy has become Combination therapy has become commonplace in the treatment of bipolar commonplace in the treatment of bipolar disorder and further studies will provide disorder and further studies will provide data on efficacy, safety and tolerability of data on efficacy, safety and tolerability of combination treatments during long term combination treatments during long term treatmenttreatment

SUMMARYSUMMARY

Diagnosis and treatment of bipolar Diagnosis and treatment of bipolar disorder, particularly mixed state can be disorder, particularly mixed state can be very difficult and has serious implicationsvery difficult and has serious implications

When choosing a treatment regimen, When choosing a treatment regimen, medications that optimizes efficacy, safety, medications that optimizes efficacy, safety, tolerability, and adherence should be tolerability, and adherence should be prioritizedprioritized

Date post:	06-May-2015
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Bipolar Disorder

Health & Medicine