New treatment New treatment options for use in options for use in

bipolar maniabipolar maniaDr C VersterDr C Verster

Dept PsychiatryDept Psychiatry

Uuniversity of StellenboschUuniversity of Stellenbosch

The Mind is its own place

and in itself can make

a Heaven a Hell,

a Hell a HeavenJohn Milton

HIGH

LOW

Normal MoodNormal Mood

HIGH

LOW

Unipolar DepressionUnipolar Depression(The Common Garden Variety)(The Common Garden Variety)

HIGH

LOW

Bipolar (II) DisorderBipolar (II) Disorder

HIGH

LOW

Bipolar (I) DisorderBipolar (I) DisorderMANIA

Trying to describe bipolar Trying to describe bipolar disorderdisorder

“The cogs of my mind are not all working together”

Case studyCase study

►32yr old female patient 32yr old female patient (Pt AB)(Pt AB)►Going through divorce; 1 child (4yrs old)Going through divorce; 1 child (4yrs old)►Working as secretaryWorking as secretary►Known with diagnosis of Bipolar I DisorderKnown with diagnosis of Bipolar I Disorder►On medication: On medication: Lithium 750mg at nightLithium 750mg at night►Progressively less sleep x 2 weeksProgressively less sleep x 2 weeks► Irritability++Irritability++

►On day of evaluation:On day of evaluation: GrandioseGrandiose Refusing medicationRefusing medication Refusing to go to workRefusing to go to work ““Don’t need psychiatrist”Don’t need psychiatrist” Praying to random people in the streetPraying to random people in the street Giving away moneyGiving away money

►Family “at wits’ end” Family “at wits’ end” ““This is the 3This is the 3rdrd such episode in 18 months” such episode in 18 months” ““She will lose her child”She will lose her child” ““Employer is fed-up”Employer is fed-up”

What now?What now?►AdmissionAdmission

She refusesShe refuses Family unable to deal with herFamily unable to deal with her Irresponsible behaviour (child’s safety)Irresponsible behaviour (child’s safety) Danger to self / reputationDanger to self / reputation

Approach to Patient with acute Approach to Patient with acute manic relapsemanic relapse

►AdmissionAdmission►SedationSedation►StabilizationStabilization►Prevention of relapsePrevention of relapse

AdmissionAdmission

►MHCAMHCA VoluntaryVoluntary InvoluntaryInvoluntary

Pt AB: Needs admission ?Involuntary - certified

SedationSedation

►BenzodiazepinesBenzodiazepines Oral/SublingualOral/Sublingual IMI/IVIIMI/IVI

►Antipsychotics (IMI)Antipsychotics (IMI) Zuclopenthixol decanoateZuclopenthixol decanoate Olanzapine IMIOlanzapine IMI Ziprasidone IMIZiprasidone IMI Haloperidol IMIHaloperidol IMI Clothiapine IMIClothiapine IMI

Pt AB:Lorazepam IMI OR Olanzepine/ Ziprasidone IMI

(NB Avoid IMI Benzo/Olanzepine combination)

StabilizationStabilization

►Behaviour / Sleep / Psychosis / MoodBehaviour / Sleep / Psychosis / Mood

What is a mood stabilizer?What is a mood stabilizer?

►Bowden (2002): A drug thatBowden (2002): A drug that benefits at least one primary aspect of benefits at least one primary aspect of

bipolar illnessbipolar illness is effective in both acute and maintenance is effective in both acute and maintenance

phasesphases does not worsen any aspect of the illness does not worsen any aspect of the illness

Traditional mood stabilizers:Traditional mood stabilizers:► lithium, valproate, carbamazepine (recently: lamotrigine)lithium, valproate, carbamazepine (recently: lamotrigine)

►Stahl 2010:Stahl 2010: Includes atypical antipsychoticsIncludes atypical antipsychotics

► Antipsychotics always used in maniaAntipsychotics always used in mania► Atypicals also have effect on bipolar depressionAtypicals also have effect on bipolar depression

(Antidepressants = mood destabilizers)(Antidepressants = mood destabilizers)

Generic Generic NameName Trade NameTrade Name ManicManic MixedMixed MaintenancMaintenanc

eeDepressionDepression

ValproateValproate Depakote(EpilDepakote(Epilim)im)

XX

CarbamazepinCarbamazepine extended e extended releaserelease

Equetro Equetro (Tegretol)(Tegretol)

XX XX

LamotrigineLamotrigine Lamictal Lamictal (Lamictin)(Lamictin)

XX

LithiumLithium XX XX

AripiprazoleAripiprazole AbilifyAbilify XX XX XX

ZiprasidoneZiprasidone GeodonGeodon XX XX

RisperidoneRisperidone RisperdalRisperdal XX XX

AsenapineAsenapine Saphris (N/A)Saphris (N/A) XX XX

QuetiapineQuetiapine SeroquelSeroquel XX XX

ChlorpromazinChlorpromazinee

Thorazine Thorazine (Largactil)(Largactil)

XX

OlanzapineOlanzapine ZyprexaZyprexa XX XX XX

Olanzapine/Olanzapine/fluoxetine fluoxetine combinationcombination

Symbyax Symbyax (N/A)(N/A)

XX

FDA Approved Bipolar Treatment RegimensFDA Approved Bipolar Treatment Regimens:

Gutman DA, Nemeroff C. Atypical Antipsychotics in Bipolar Disorder. Medscape. Available at http://www.medscape.com/viewarticle/554128. Accessed June 27, 2007

2011 2011 (Sachs et al; J Clin Psych)(Sachs et al; J Clin Psych)

► Category A evidence (Double blind placebo Category A evidence (Double blind placebo controlled trials; adequate sample)controlled trials; adequate sample)

► Efficacy for acute mania:Efficacy for acute mania: LithiumLithium ValproateValproate CarbamazepineCarbamazepine OlanzapineOlanzapine RisperidoneRisperidone ZiprasidoneZiprasidone HaloperidolHaloperidol QuetiapineQuetiapine AripirazoleAripirazole PaliperidonePaliperidone AsenapineAsenapine

LithiumLithium

►Used since the 1950’sUsed since the 1950’s►Effective mood stabilizerEffective mood stabilizer►Narrow therapeutic rangeNarrow therapeutic range

(Blood levels monitored)(Blood levels monitored)►ToxicityToxicity

AcuteAcute ChronicChronic

►ThyroidThyroid►KidneysKidneys

Pt AB: No use as sedative Why did she relapse? Why did she refuse medication? May still be of use in long

term management

Anti EpilepticsAnti Epileptics

►Carbamazepine / Valproate / Carbamazepine / Valproate / LamotrigineLamotrigine

Pt AB: Limited efficacy in mania Side effect profile Pregnancy?

AntipsychoticsAntipsychotics

►TypicalsTypicals HaloperidolHaloperidol ZuclopenthixolZuclopenthixol ChlorpromazineChlorpromazine

►Effective, but poor side-effect profileEffective, but poor side-effect profile

Atypical antipsychoticsAtypical antipsychotics

Why maintenance therapy?Why maintenance therapy?

►Prevention of relapsePrevention of relapse ±80% relapse within 1 year without ±80% relapse within 1 year without

medicationmedication ±20% relapse within 1 year with ±20% relapse within 1 year with

medicationmedication In practice: ±50% relapse within 1In practice: ±50% relapse within 1stst year year

►Because of poor treatment adherenceBecause of poor treatment adherence

Cost of relapseCost of relapse

►Hospitalization (may be for weeks)Hospitalization (may be for weeks) R700-2000 per dayR700-2000 per day PMBPMB

►Social & occupational consequencesSocial & occupational consequences

Reason for poor adherenceReason for poor adherence► Poor psychoeducationPoor psychoeducation

Lack of insightLack of insight Poor understanding of illnessPoor understanding of illness

► Side-effectsSide-effects► Cost factorsCost factors► Social pressure/stigmaSocial pressure/stigma► Dosage interval / amount of tabletsDosage interval / amount of tablets► Religious / cultural factorsReligious / cultural factors► Availability of medicationAvailability of medication► Substance abuseSubstance abuse► Severity of illnessSeverity of illness

Stabilization/MaintenanceStabilization/MaintenanceEvideEvidencence

EPSEPS Prol.Prol. Sed.Sed. WeightWeightGainGain

TD TD NMSNMS CVS CVS RiskRisk

OtherOther CostCost

Typicals Typicals (↑potency)(↑potency)

++ ++++++

++++ +(++)+(++) ++ ++++++ ++++++ ±± ++

Typicals Typicals (↓potency)(↓potency)

±± ++++ ++++ ++++++ ++++ ++ ++ ++ ++

AmisulpirideAmisulpiride -- ++++ ++++++

++++ ++ ++ ++ ++++ ++++++

AripiprazoleAripiprazole ++ +/++/+++

(Akathisia(Akathisia))

-- -- ±± ±± ±± ?-?- ++++++++

ClozapineClozapine -- ±± -- ++++++++

++++++++

±± ++++ ++ AgranulocyAgranulocyt.t.

MiocarditisMiocarditisHypersaliv.Hypersaliv.

++(+)++(+)

OlanzapineOlanzapine ++ ++ -- ++++ ++++++ ++ ++ ++ RashRash ++++

QuetiapineQuetiapine ++ ±± -- ++++++ ++++ -- ±± ++ +++(+)+++(+)

Risperidone/Risperidone/PaliperidonePaliperidone

++ ++++ ++++ ++++ ++++ ±± ±± ++ ++++++++++++

ZiprasidoneZiprasidone ++ ++ -- ±± ±± ±± ±± ++++ Food effectFood effect ++++++++

Stahl, SM. The Prescriber’s Guide 3rd ed; 2009

Pt ABPt AB

►Stabilize! Stabilize! ►Psychoeducation – also family!Psychoeducation – also family!►Lithium levels → discontinue or not?Lithium levels → discontinue or not?►Monotherapy or combination?Monotherapy or combination?► Illness profileIllness profile

Sleeping patternSleeping pattern Depressive episodes?Depressive episodes? Cost factorsCost factors

NB Bipolar Disorder should be managed by a psychiatrist